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Individuals diagnosed with Parkinson's disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background and Aims: Acetaminophen (APAP) hepatotoxicity and ischemic hepatic injury (IH) demonstrate remarkably similar biochemical patterns. Deciding between these two etiologies in the setting of acute liver failure (ALF) can be challenging. We reviewed all cases in the Acute Liver Failure Study Group (ALFSG) registry where these diagnoses were considered, to determine reasons for, and frequency of, difficulties making these diagnoses. We hypothesized that the newly developed APAP-CYS adduct assay could help in discerning the correct diagnosis. Methods: Among 3364 patients with ALF or acute liver injury (ALI: INR ≥ 2.0 but without encephalopathy) between 1998 and 2019, 1952 (58%) received a final diagnosis of either APAP (1681) or IH (271). We utilized a review committee of senior hepatologists as well as the APAP-CYS assay (where sera were available), measuring the presence of toxic by-products of APAP injury to optimize adjudication. Results: With these methods, a total of 575 adduct positive APAP cases included 488 recognized APAP, as well as an additional 87 patients previously diagnosed as other etiologies. Nine cases initially attributed to IH were deemed combination APAP-IH injuries. Conversely, 215 of the 280 IH subjects tested for adducts disclosed 173 confirmed as IH with adduct testing below the toxicity threshold, while 9 cases were revised from APAP to the IH-APAP combination phenotype, where both hypotension and APAP likely played a role. Conclusions: Discerning APAP from IH can be difficult—in rare cases, combined injury is observed (18/1952). APAP-CYS testing resulted in revising the diagnosis in 14.6% of cases. [ABSTRACT FROM AUTHOR]

Background & Objective: One third of the neonatal deaths worldwide are attributed to perinatal asphyxia. We aimed to determine the prevalence and determinants of cardiac dysfunction, through echocardiographic evaluation, in term neonates with perinatal asphyxia. Methods: This cross-sectional study was conducted at a tertiary care setting over a period of six months from 1st January 2021 to 30th June 2021. Term neonates, weighing ≥ 2500 grams, born with Apgar score < 7 and admitted within 48-hours of life were consecutively enrolled. Using Levene classification neonates were grouped into moderate and severe perinatal asphyxia. All neonates underwent transthoracic echocardiographic evaluation after 24-hours of stabilization and within 72-hours of life. Descriptive statistics are calculated, and logistic regression analysis is done to determine the risk factors of myocardial dysfunction. Results: Among 166 neonates, 53% (n=88) were males, mean gestational age was 38.1 ± 0.89 weeks. Moderate asphyxia was present in 121 (72.9%). Most common echocardiographic finding was pulmonary hypertension in 50% followed by patent ductus arteriosus (PDA) in 37.2% and mitral regurgitation in 6.6%. Myocardial dysfunction was detected in 28.9% of the neonates. Three independent determinants of myocardial dysfunction were severe asphyxia [adjusted odds ratio (aOR) 5.01, 95% CI 2.2-11.4; p-value <0.001], having patent ductus arteriosus (aOR 5.11, 95% CI 2.2-11.8; p-value < 0.001) and delivery through cesarean section (aOR 2.65, 95% CI 1.2-5.9; p-value 0.02). Conclusions: Myocardial dysfunction among neonates with perinatal asphyxia is common and severity of asphyxia, mode of delivery and presence of patent ductus arteriosus are important determinants. [ABSTRACT FROM AUTHOR]

Na+-K+ ATPase is an integral component of cardiac sarcolemma and consists of three major subunits, namely the α-subunit with three isoforms (α1, α2, and α3), β-subunit with two isoforms (β1 and β2) and γ-subunit (phospholemman). This enzyme has been demonstrated to transport three Na and two K ions to generate a trans-membrane gradient, maintain cation homeostasis in cardiomyocytes and participate in regulating contractile force development. Na+-K+ ATPase serves as a receptor for both exogenous and endogenous cardiotonic glycosides and steroids, and a signal transducer for modifying myocardial metabolism as well as cellular survival and death. In addition, Na+-K+ ATPase is regulated by different hormones through the phosphorylation/dephosphorylation of phospholemman, which is tightly bound to this enzyme. The activity of Na+-K+ ATPase has been reported to be increased, unaltered and depressed in failing hearts depending upon the type and stage of heart failure as well as the association/disassociation of phospholemman and binding with endogenous cardiotonic steroids, namely endogenous ouabain and marinobufagenin. Increased Na+-K+ ATPase activity in association with a depressed level of intracellular Na+ in failing hearts is considered to decrease intracellular Ca2+ and serve as an adaptive mechanism for maintaining cardiac function. The slight to moderate depression of Na+-K+ ATPase by cardiac glycosides in association with an increased level of Na+ in cardiomyocytes is known to produce beneficial effects in failing hearts. On the other hand, markedly reduced Na+-K+ ATPase activity associated with an increased level of intracellular Na+ in failing hearts has been demonstrated to result in an intracellular Ca2+ overload, the occurrence of cardiac arrhythmias and depression in cardiac function during the development of heart failure. Furthermore, the status of Na+-K+ ATPase activity in heart failure is determined by changes in isoform subunits of the enzyme, the development of oxidative stress, intracellular Ca2+-overload, protease activation, the activity of inflammatory cytokines and sarcolemmal lipid composition. Evidence has been presented to show that marked alterations in myocardial cations cannot be explained exclusively on the basis of sarcolemma alterations, as other Ca2+ channels, cation transporters and exchangers may be involved in this event. A marked reduction in Na+-K+ ATPase activity due to a shift in its isoform subunits in association with intracellular Ca2+-overload, cardiac energy depletion, increased membrane permeability, Ca2+-handling abnormalities and damage to myocardial ultrastructure appear to be involved in the progression of heart failure. [ABSTRACT FROM AUTHOR]

Chronic psychological stress is a recognized, yet understudied risk factor for heart disease, with potential sex-specific effects. We investigated whether chronic stress triggers sex-dependent cardiac dysfunction in isolated Wistar rat hearts subjected to ischemia-reperfusion injury. The experimental cohort underwent 1 h of daily restraint stress for 4 wk versus matched controls, followed by euthanasia (sodium pentobarbital) and heart excision for ex vivo perfusion. Blood analysis revealed sex-specific alterations in stress hormones and inflammatory markers. When compared with controls, chronic restraint stress (CRS) males displayed decreased plasma brain-derived neurotrophic factor (BDNF) levels (P < 0.05), whereas CRS females exhibited elevated plasma adrenocorticotropic hormone (ACTH) (P < 0.01) and reduced corticosterone (P < 0.001) alongside lower serum estradiol (P < 0.001) and estradiol/progesterone ratio (P < 0.01). Of note, CRS females showed increased serum cardiac troponin T (P < 0.05) and tumor necrosis factor-α (TNF-α) (P < 0.01) with suppressed interleukin (IL)-1α, IL-1β, IL-6, and IL-10 levels (P < 0.05) when compared with controls. Ex vivo Langendorff perfusions revealed that CRS female hearts displayed impaired postischemic functional recovery for baseline stroke volume (SV, P < 0.01), work performance (P < 0.05), aortic output (AO, P < 0.05), coronary flow (CF, P < 0.01), and overall cardiac output (CO, P < 0.01) when compared with matched controls and CRS males (P < 0.05). Our findings reveal intriguing sex-specific responses at both the systemic and functional levels in stressed hearts. Here, the dysregulation of stress hormones, proinflammatory state, and potential underlying cardiomyopathy in females following the stress protocol renders them more prone to damage following myocardial ischemia. This study emphasizes the importance of incorporating sex as a biological variable in cardiac research focusing on stress-related cardiomyopathy. NEW & NOTEWORTHY: Although chronic psychological stress is a risk factor for cardiovascular diseases, the underlying mechanisms remain poorly understood. This study revealed that chronic restraint stress resulted in systemic changes (dysregulated stress hormones, proinflammatory state) and potential cardiomyopathy in females versus controls and their male counterparts. The stressed female hearts also displayed reduced functional recovery following ex vivo ischemia-reperfusion. This highlights the importance of incorporating sex as a biological variable in cardiac research. [ABSTRACT FROM AUTHOR]

Objectives: The influence of lung resection on cardiac function has been reported, and previous studies have mainly focused on right ventricular (RV) dysfunction. As few studies have analyzed changes in left ventricular hemodynamic variables caused by lung resection, we aimed to investigate the perioperative changes in left ventricular stroke volume (LVSV) caused by anatomical lung resection. Methods: We enrolled 61 patients who underwent anatomical lung resection and perioperative LVSV monitoring. The Flo Trac system was used for dynamic monitoring. We investigated changes in LVSV after lung resection and the factors that affected these changes. The operative procedures that contributed to these changes were also investigated. Results: LVSV decreased after anatomical lung resection in the majority of patients (n = 38, 62.2%). Operative procedures affecting this change were (a) taping the superior pulmonary vein (SPV; right: V1‐3) before dorsal part procedure (e.g., major fissure division of right upper lobectomy, A1 + 2c, and A4 + 5 division of left upper lobectomy); (b) division of the SPV (right: V1‐3, V4 + 5); (c) division of A6‐10 (in lower lobectomy); and (d) finish division of all vessels. Conclusions: LVSV decrease was caused by anatomical lung resection in the majority of patients owing to the intraoperative procedures described above. [ABSTRACT FROM AUTHOR]

Background: Traumatic brain injury (TBI) causes significant changes in myocardial function, which is represented by ECG and echocardiographic changes. We intended to study the effect of surgical decompression on these changes. Materials and methods: We recruited adult TBI patients undergoing surgery within 48 h of injury. Preoperatively, the patient's demographic and clinical details were recorded. ECG and TTE were performed before surgery and 24 h later (first postoperative day [POD1]). ECG was analyzed for heart rate, PR, QRS, and QTc intervals, morphologic end-repolarization abnormalities (MERA), and ST-segment and T wave changes. TTE data included left ventricular ejection fraction (LVEF) and regional wall motion abnormalities (RWMA). Glasgow coma scale (GCS) at discharge was recorded. ECG and TTE changes before and after surgery were compared, and its association with discharge GCS was analyzed. Preoperative predictors of LV dysfunction were analyzed. Results: Of the 110 patients recruited, common ECG changes were prolonged QTc interval (42%) and MERA (47%). TTE showed poor LVEF (<50%) in 10% and RWMA in 10.8% of patients. Following surgery, both ECG and TTE changes improved. Preoperative LVEF <50% and/or RWMA were associated with a lower GCS score at discharge. Preoperative poor GCS motor score and prolonged QTc interval were independent predictors of LV dysfunction. Conclusions: Poor LV function was associated with poor admission GCS and prolonged QTc interval. Patients with reduced LV function had lower GCS at discharge. [ABSTRACT FROM AUTHOR]

Aging is a critical risk factor for heart disease, including ischemic heart disease and heart failure. Cellular senescence, characterized by DNA damage, resistance to apoptosis and the senescence-associated secretory phenotype (SASP), occurs in many cell types, including cardiomyocytes. Senescence precipitates the aging process in surrounding cells and the organ through paracrine mechanisms. Generalized autophagy, which degrades cytosolic materials in a non-selective manner, is decreased during aging in the heart. This decrease causes deterioration of cellular quality control mechanisms, facilitates aging and negatively affects lifespan in animals, including mice. Although suppression of generalized autophagy could promote senescence, it remains unclear whether the suppression of autophagy directly stimulates senescence in cardiomyocytes, which, in turn, promotes myocardial dysfunction in the heart. We addressed this question using mouse models with a loss of autophagy function. Suppression of general autophagy in cardiac-specific Atg7 knockout (Atg7 cKO) mice caused accumulation of senescent cardiomyocytes. Induction of senescence via downregulation of Atg7 was also observed in chimeric Atg7 cardiac-specific KO mice and cultured cardiomyocytes in vitro , suggesting that the effect of autophagy suppression upon induction of senescence is cell autonomous. ABT-263, a senolytic agent, reduced the number of senescent myocytes and improved cardiac function in Atg7 cKO mice. Suppression of autophagy and induction of senescence were also observed in doxorubicin-treated hearts, where reactivation of autophagy alleviated senescence in cardiomyocytes and cardiac dysfunction. These results suggest that suppression of general autophagy directly induces senescence in cardiomyocytes, which in turn promotes cardiac dysfunction. [Display omitted] • Inhibition of autophagy by downregulation of Atg7 in cardiomyocytes promotes cardiac senescence. • Doxorubicin diminishes autophagic flux and causes cardiomyocyte senescence. • Increased cardiac senescence due to loss of Atg7 or doxorubicin treatment results in cardiac dysfunction. • Activation of autophagy by Beclin 1(T106A) attenuates doxorubicin-induced senescence and cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. We examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into 3 equal-sized groups (low VEGF <500 ng/liter, n = 28; moderate VEGF 500–3000 ng/liter, n = 28; and high VEGF >3000 ng/liter, n = 27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for 5 years. Baseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. Our findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria. [ABSTRACT FROM AUTHOR]

Stroke–heart syndrome (SHS), a critical yet underrecognized condition, encompasses a range of cardiac complications that arise following an ischemic stroke. This narrative review explores the pathophysiology, clinical manifestations, and implications of SHS, focusing on the complex interplay between the brain and the heart. Acute ischemic stroke (AIS) triggers autonomic dysfunction, leading to a surge in catecholamines and subsequent myocardial injury. Our review highlights the five cardinal manifestations of SHS: elevated cardiac troponin (cTn) levels, acute myocardial infarction, left ventricular dysfunction, arrhythmias, and sudden cardiac death. Despite the significant impact of these complications on patient outcomes, there is a notable absence of specific guidelines for their management. Through a comprehensive literature search, we synthesized findings from recent studies to elucidate the mechanisms underlying SHS and identified gaps in the current understanding. Our findings underscore the importance of early detection and multidisciplinary management of cardiac complications post-stroke. Future research should focus on establishing evidence-based protocols to improve clinical outcomes for stroke patients with SHS. Addressing this unmet need will enhance the care of stroke survivors and reduce mortality rates associated with cardiac complications. [ABSTRACT FROM AUTHOR]

High-altitude exposure has been linked to cardiac dysfunction. Silent information regulator factor 2-related enzyme 1 (sirtuin 1, SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, plays a crucial role in regulating numerous cardiovascular diseases. However, the relationship between SIRT1 and cardiac dysfunction induced by hypobaric hypoxia (HH) remains unexplored. This study aims to assess the impact of SIRT1 on HH-induced cardiac dysfunction and delve into the underlying mechanisms, both in vivo and in vitro. In this study, we have demonstrated that exposure to HH results in cardiomyocyte injury, along with the downregulation of SIRT1 and mitochondrial dysfunction. Upregulating SIRT1 significantly inhibits mitochondrial fission, improves mitochondrial function, reduces cardiomyocyte injury, and consequently enhances cardiac function in HH-exposed rats. Additionally, HH exposure triggers aberrant expression of mitochondrial fission-regulated proteins, with a decrease in PPARγ coactivator 1 alpha (PGC-1α) and mitochondrial fission factor (MFF) and an increase in mitochondrial fission 1 (FIS1) and dynamin-related protein 1 (DRP1), all of which are mitigated by SIRT1 upregulation. Furthermore, inhibiting PGC-1α diminishes the positive effects of SIRT1 regulation on the expression of DRP1, MFF, and FIS1, as well as mitochondrial fission. These findings demonstrate that SIRT1 alleviates HHinduced cardiac dysfunction by preventing mitochondrial fission through the PGC-1α-DRP1/FIS1/MFF pathway. [ABSTRACT FROM AUTHOR]

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy. [ABSTRACT FROM AUTHOR]

Cabozantinib, a multi-kinase receptor inhibitor, is utilized in the treatment of advanced malignancies such as metastatic renal cancers. While rare, cabozantinib-induced cardiotoxicity has emerged as a recognized adverse effect with potentially reversible outcomes. We report the case of a 55-year-old male who developed fatal cardiomyopathy 4 months after initiating cabozantinib therapy. Despite its rarity, cardiomyopathy after initiation of cabozantinib can be lethal if not diagnosed early. This case underscores a significant gap in the surveillance of patients treated with newer agents like cabozantinib. Larger observational studies are needed to assess the prevalence and impact of cardiomyopathy after initiation of cabozantinib therapy, and to determine the cost–effectiveness of early surveillance protocols. Article highlights Background Tyrosine kinase inhibitors (TKIs) have significantly improved cancer survival rates but carry risks of severe adverse effects, including cardiotoxicity. Cabozantinib is a potent TKI used for advanced renal cell carcinoma, hepatocellular carcinoma and medullary thyroid carcinoma. Case presentation A 59-year-old male with a history of metastatic renal cell carcinoma and prior heart conditions developed fatal cardiomyopathy 4 months after starting cabozantinib. Initial symptoms included shortness of breath, pedal swelling and weight gain, progressing rapidly to cardiogenic shock. Discussion Cabozantinib-induced cardiomyopathy, though rare, can result from VEGFR inhibition affecting cardiac myocytes. Current guidelines recommend regular cardiac monitoring for early detection of cardiotoxicity in patients on TKIs. Our case reveals potential gaps in surveillance, suggesting the need for improved monitoring protocols. Conclusion Early cardiac monitoring in patients on cabozantinib is crucial for preventing fatal outcomes. Larger studies are needed to understand the incidence and burden of cabozantinib-induced cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions To conduct a systematic review in order to better understand the association of glycaemic risk factors and diabetes duration with risk of heart failure (HF) in individuals with type 2 diabetes (T2D).We identified longitudinal studies investigating the association of glycaemic factors (glycated haemoglobin [HbA1c], HbA1c variability, and hypoglycaemia) and diabetes duration with HF in individuals with T2D. Hazard ratios and odds ratios were extracted and meta‐analysed using a random‐effects model where appropriate. Risk of bias assessment was carried out using a modified Newcastle–Ottawa Scale. Egger's test along with the trim‐and‐fill method were used to assess and account for publication bias.Forty studies representing 4 102 589 people met the inclusion criteria. The risk of developing HF significantly increased by 15% for each percentage point increase in HbA1c, by 2% for each additional year of diabetes duration, and by 43% for having a history of severe hypoglycaemia. Additionally, variability in HbA1c levels was associated with a 20%–26% increased risk of HF for each unit increase in the metrics of variability (HbA1c standard deviation, coefficient of variation, and average successive variability). All included studies scored high in the risk of bias assessment. Egger's test suggested publication bias, with trim‐and‐fill analyses revealing a significant 14% increased risk of HF per percentage point increase in HbA1c.Glycaemic risk factors and diabetes duration significantly contribute to the heightened risk of HF among individuals with T2D. A reduction in risk of HF is anticipated with better management of glycaemic risk factors. [ABSTRACT FROM AUTHOR]

Cellular Communication Network Factor 2 (CCN2) is a matricellular protein implicated in cell communication and microenvironmental signaling. Overexpression of CCN2 has been documented in various cardiovascular pathologies, wherein it may exert either deleterious or protective effects depending on the pathological context, thereby suggesting that its role in the cardiovascular system is not yet fully elucidated. In this study, we aimed to investigate the effects of Ccn2 gene deletion on the progression of acute cardiac injury induced by doxorubicin (DOX), a widely utilized chemotherapeutic agent. To this end, we employed conditional knockout (KO) mice for the Ccn2 gene (CCN2-KO), which were administered DOX and compared to DOX-treated wild-type (WT) control mice. Our findings demonstrated that the ablation of CCN2 ameliorated DOX-induced cardiac dysfunction, as evidenced by improvements in ejection fraction (EF) and fractional shortening (FS) of the left ventricle. Furthermore, DOX-treated CCN2-KO mice exhibited a significant reduction in the gene expression and activation of oxidative stress markers (Hmox1 and Nfe2l2/NRF2) relative to DOX-treated WT controls. Additionally, the deletion of Ccn2 markedly attenuated DOX-induced cardiac fibrosis. Collectively, these results suggest that CCN2 plays a pivotal role in the pathogenesis of DOX-mediated cardiotoxicity by modulating oxidative stress and fibrotic pathways. These findings provide a novel avenue for future investigations to explore the therapeutic potential of targeting CCN2 in the prevention of DOX-induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Cardiotoxicity can develop as a result of exposure to certain chemicals, poisons, or infectious agents as well as the continued use of higher doses of some medications. Natural plant foods such as cashew nut (Anacardium occidentale L.) may have free radical scavenging activity, thereby may play an important role in protecting the heart from chemotherapy-related cardiac dysfunction. In this study, the effect of cashew nut-supplemented diet on key indices relevant to cardiac function in cisplatin-induced cardiotoxic rats was evaluated. The rats were divided into six groups (n=6): rats fed a basal diet; cisplatin-induced rats fed a basal diet; cisplatin-induced rats fed a diet supplemented with processed cashew nut (10 and 20%); healthy rats fed a diet supplemented with processed cashew nut (10 and 20%) for fourteen days. Cisplatin-treated rats showed increased activities of acetylcholinesterase and butyrylcholinesterase, adenosine deaminase, monoamine oxidase, phosphodiesterase-5 and arginase activities with a concomitant decrease in levels of nitric oxide, total thiol, total antioxidant capacity and reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase activities both in the heart and plasma when compared with control. However, dietary supplementation with cashew nut significantly attenuated the cisplatin-evoked disturbances in the above-mentioned parameters. Also, feeding of experimental rats with cashew nut-supplemented diet for fourteen days restores significantly the heart histological alteration caused by cisplatin. Taken together, these findings imply that eating cashew nuts may represent a novel cardioprotective strategy during chemotherapy based on cisplatin. Therefore, it could be used as functional diet to prevent cardiac dysfunction caused by cisplatin. [ABSTRACT FROM AUTHOR]

Background: The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed to predict extubation outcomes. However, few studies focused on the predicting value of E/Ea and DE at different positions during a spontaneous breathing trial (SBT), as well as the effects of △E/Ea and △DE (changes in E/Ea and DE during a SBT). Methods: This study was a reanalysis of the data of 60 difficult-to-wean patients in a previous study published in 2017. All eligible participants were organized into respiratory failure (RF) group and extubation success (ES) group within 48 h after extubation, or re-intubation (RI) group and non-intubation (NI) group within 1 week after extubation. The risk factors for respiratory failure and re-intubation including E/Ea and △E/Ea, DE and △DE at different positions were analyzed by multivariate logistic regression, respectively. The receiver operating characteristic (ROC) curves of E/Ea (septal, lateral, average) and DE (right, left, average) were compared with each other, respectively. Results: Of the 60 patients, 29 cases developed respiratory failure within 48 h, and 14 of those cases required re-intubation within 1 week. Multivariate logistic regression showed that E/Ea were all associated with respiratory failure, while only DE (right) and DE (average) after SBT were related to re-intubation. There were no statistic differences among the ROC curves of E/Ea at different positions, nor between the ROC curves of DE. No statistical differences were shown in △E/Ea between RF and ES groups, while △DE (average) was remarkably higher in NI group than that in RI group. However, multivariate logistic regression analysis showed that △DE (average) was not associated with re-intubation. Conclusions: E/Ea at different positions during a SBT could predict postextubation respiratory failure with no statistical differences among them. Likewise, only DE (right) and DE (average) after SBT might predict re-intubation with no statistical differences between each other. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to evaluate, for the first time, the diagnostic value of long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) in sepsis and its molecular mechanisms in sepsis-induced inflammation and cardiac dysfunction. Material and methods: A total of 126 sepsis patients and 81 healthy controls were enrolled. Serum SNHG8 levels were assessed by RT-qPCR. Levels of pro-inflammatory factors were examined via ELISA. The ROC curve was employed to assess the diagnostic significance of SNHG8. Cardiomyocytes were exposed to lipopolysaccharide (LPS) to simulate sepsis-induced cardiac dysfunction in vitro. Cell proliferation and apoptosis were measured through CCK-8 and flow cytometry. Dual luciferase reporter gene assay and RIP assay were conducted to verify the target relationship between SNHG8 and miR-34b-5p. Results: SNHG8 was reduced in sepsis patients (p < 0.05) and negatively correlated with procalcitonin, C-reactive protein, and pro-inflammatory factors (p < 0.05). SNHG8 had outstanding performance in distinguishing sepsis patients from healthy individuals with the AUC of 0.878. Among septic patients, those with cardiac dysfunction had significantly downregulated SNHG8 levels (p < 0.05). For septic patients, SNHG8 was found to be an independent predictor for the occurrence of cardiac dysfunction (HR = 5.466, 95% CI = 2.230-13.397, p < 0.001). Elevated SNHG8 reversed LPS-induced cell apoptosis, and attenuated the over-secretion of inflammatory factors. miR-34b-5p was significantly upregulated in septic patients and negatively correlated with SNHG8, indicating that it acted as a sponge for SNHG8. Conclusions: Reduced SNHG8 is a potential diagnostic biomarker for sepsis. It is involved in sepsis-induced inflammatory response and cardiac dysfunction through sponging miR-34b-5p. [ABSTRACT FROM AUTHOR]

Chemotherapy has markedly improved cancer outcomes, yet cancer therapy-related cardiac dysfunction (CTRCD) poses a significant challenge, affecting around 10% of patients. CTRCD can be asymptomatic or present with heart failure symptoms. Multimodality imaging, particularly echocardiography, remains pivotal for monitoring cardiac function. Potential biomarkers for CTRCD assessment include troponin and B-type natriuretic peptide. Pharmacological interventions, such as dexrazoxane, angiotensinconverting enzyme inhibitors, and statins, play a crucial role in primary prevention and mitigating cardiotoxicity alongside cardiac rehabilitation programs. Thus, a comprehensive approach is essential for optimal cardiac recovery and improved patient outcomes. [ABSTRACT FROM AUTHOR]

The YTH-domain family (YTHDF) of RNA binding proteins can control gene expression at the post-transcriptional level by regulating mRNAs with N6-methyladenosine (m6A) modifications. Despite the established importance of m6A in the heart, the cardiac role of specific m6A-binding proteins remains unclear. Here, we characterized the function of YTHDF1 in cardiomyocytes using a newly generated cardiac-restricted mouse model. Deletion of YTHDF1 in adult cardiomyocytes led to hypertrophy, fibrosis, and dysfunction. Using mass spectrometry, we identified the necessity of YTHDF1 for the expression of cardiomyocyte membrane raft proteins. Specifically, YTHDF1 bound to m6A-modified Caveolin 1 (Cav1) mRNA and favored its translation. We further demonstrated that YTHDF1 regulates downstream ERK signaling. Altogether, our findings highlight a novel role for YTHDF1 as a post-transcriptional regulator of caveolar proteins which is necessary for the maintenance of cardiac function. [Display omitted] • Loss of YTHDF1 in cardiomyocytes perturbs cardiac homeostasis. • Loss of YTHDF1 impacts the cardiomyocyte's proteome. • YTHDF1 regulates the expression of caveolin-1. • YTHDF1 affects ERK1/2 signaling downstream of adrenergic receptors. [ABSTRACT FROM AUTHOR]

Stroke can lead to cardiac complications such as arrhythmia, myocardial injury, and cardiac dysfunction, collectively termed stroke–heart syndrome (SHS). These cardiac alterations typically peak within 72 h of stroke onset and can have long-term effects on cardiac function. Post-stroke cardiac complications seriously affect prognosis and are the second most frequent cause of death in patients with stroke. Although traditional vascular risk factors contribute to SHS, other potential mechanisms indirectly induced by stroke have also been recognized. Accumulating clinical and experimental evidence has emphasized the role of central autonomic network disorders and inflammation as key pathophysiological mechanisms of SHS. Therefore, an assessment of post-stroke cardiac dysautonomia is necessary. Currently, the development of treatment strategies for SHS is a vital but challenging task. Identifying potential key mediators and signaling pathways of SHS is essential for developing therapeutic targets. Therapies targeting pathophysiological mechanisms may be promising. Remote ischemic conditioning exerts protective effects through humoral, nerve, and immune-inflammatory regulatory mechanisms, potentially preventing the development of SHS. In the future, well-designed trials are required to verify its clinical efficacy. This comprehensive review provides valuable insights for future research. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remains unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods As part of the MESA study, 3 045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010 and 2012. Of these, 1 743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up exam: 2016–2018) which were used to generate a binary combined frail/prefrail versus robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction). Results Participants were 66 ± 8 years, 52% female at the time of imaging, and 29.4% were classified as frail or prefrail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (odds ratio [OR] 1.89, p  = .008; Coef. −52.9, p  < .001), increased ECV (OR 1.10, p  = .002; Coef. −4.0, p  = .001), and worsening left atrial strain rate at early diastole (OR 1.56, p ≤.001; Coef. −22.75, p  = .027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m). All associations with 6MWT performance were attenuated with adjustments for risk factors whereas ECV and LA strain rate remained independently associated with frailty. Conclusions These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis, and physical frailty. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors are at risk for cardiac dysfunction and impaired physical performance, though underlying cellular mechanisms are not well studied. In this cross-sectional study, we examined the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN, a proxy for mitochondrial function) and markers of performance impairment and cardiac dysfunction. Methods: Whole-genome sequencing, validated by quantitative polymerase chain reaction, was used to estimate mtDNA-CN in 1720 adult survivors of childhood cancer (48.5% female; mean age = 30.7 years, standard deviation (SD) = 9.0). Multivariable logistic regression was performed to evaluate the associations between mtDNA-CN and exercise intolerance, walking inefficiency, and abnormal global longitudinal strain (GLS), adjusting for treatment exposures, age, sex, and race and ethnicity. Results: The prevalence of exercise intolerance, walking inefficiency, and abnormal GLS among survivors was 25.7%, 10.7%, and 31.7%, respectively. Each SD increase of mtDNA-CN was associated with decreased odds of abnormal GLS (adjusted odds ratio (OR) = 0.88, p = 0.04) but was not associated with exercise intolerance (OR = 1.02, p = 0.76) or walking inefficiency (OR = 1.06, p = 0.46). Alkylating agent exposure was associated with increased odds of exercise intolerance (OR = 2.25, p < 0.0001), walking inefficiency (OR = 2.37, p < 0.0001), and abnormal GLS (OR = 1.78, p = 0.0002). Conclusions: Increased mtDNA-CN is associated with decreased odds of abnormal cardiac function in childhood cancer survivors. Implications for Cancer Survivors: These findings demonstrate a potential role for mtDNA-CN as a biomarker of early cardiac dysfunction in this population. [ABSTRACT FROM AUTHOR]

Abstract Objectives The influence of lung resection on cardiac function has been reported, and previous studies have mainly focused on right ventricular (RV) dysfunction. As few studies have analyzed changes in left ventricular hemodynamic variables caused by lung resection, we aimed to investigate the perioperative changes in left ventricular stroke volume (LVSV) caused by anatomical lung resection. Methods We enrolled 61 patients who underwent anatomical lung resection and perioperative LVSV monitoring. The Flo Trac system was used for dynamic monitoring. We investigated changes in LVSV after lung resection and the factors that affected these changes. The operative procedures that contributed to these changes were also investigated. Results LVSV decreased after anatomical lung resection in the majority of patients (n = 38, 62.2%). Operative procedures affecting this change were (a) taping the superior pulmonary vein (SPV; right: V1‐3) before dorsal part procedure (e.g., major fissure division of right upper lobectomy, A1 + 2c, and A4 + 5 division of left upper lobectomy); (b) division of the SPV (right: V1‐3, V4 + 5); (c) division of A6‐10 (in lower lobectomy); and (d) finish division of all vessels. Conclusions LVSV decrease was caused by anatomical lung resection in the majority of patients owing to the intraoperative procedures described above.

Sepsis triggers myocardial injury and dysfunction, leading to a high mortality rate in patients. Cardiomyocyte apoptosis plays a positive regulatory role in septic myocardial injury and dysfunction. However, the mechanism is unclear.

The development and creation of innovative therapeutic supplements and medications with extraordinary efficacy for addressing severe diabetes are of utmost importance to both developing and developed nations. A bio-inspired method has been documented for producing copper nanoparticles (CuNPs) using Pistacia atlantica leaf extract as a natural stabilizing agent. This approach is applicable, easy, and environmentally friendly, as it avoids using any toxic or harmful reagents. The CuNPs that were synthesized through biological processes underwent characterization using sophisticated physicochemical methods such as energy-dispersive X-ray spectroscopy, transmission electron microscopy, field emission-scanning electron microscopy, and Fourier-transformed infrared spectroscopy. It is confirmed that CuNPs exhibit a spherical structure, with an average size ranging from approximately 30 to 70 nm. Diabetes was induced in vivo through a fructose-enriched diet combined with streptozotocin. Half the subjects were administered CuNPs (100 µg/kg) via oral gavage. In contrast to the animals that were given regular food, the diabetic animals revealed an increase in serum fasting glucose level and a decrease in glucose tolerance. The administration of CuNPs had a significant impact on reducing glucose intolerance and fasting hyperglycemia. Additionally, it helped alleviate the negative effects of diabetes on cardiac output and work. Furthermore, utilizing CuNPs effectively hindered the rise in cardiac signal transducer and activator of transcription 3-phosphorylation caused by diabetes. The findings from this investigation provide evidence of the therapeutic benefits of CuNPs in mitigating diabetes-induced cardiac dysfunction in rats.

Abstract Background Radiation therapy (RT) for breast cancer (BC) can result in subtle cardiac dysfunction that can occur early after treatment. In 2022, the European Society of Cardiology (ESC) published the first guidelines in cardio-oncology with a harmonized definition of cancer therapy-related cardiac dysfunction (CTRCD). The aim of this study was to evaluate CTRCD occurrence over 24 months of follow-up after RT in BC patients and to analyze the association with cardiac radiation exposure. Methods The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40–75 years, with conventional and 2D Speckle tracking echocardiography performed before RT, 6 and 24 months after RT. Based on ESC cardio-oncology guidelines, CTRCD and corresponding severity were defined with left ventricle ejection fraction and global longitudinal strain decrease, occurring at 6 or 24 months after RT. Dosimetry for whole heart, left ventricle (LV) and left coronary artery (left anterior descending and circumflex arteries (CX)) was considered to evaluate the association with CTRCD, based on logistic regressions (Odds Ratio – OR and 95% confidence interval – 95%CI). Youden index based on receiver operating characteristic curve analysis was used to identify the optimal threshold of dose-volume parameters for predicting CTRCD. Results The study included 72 BC patients with a mean age of 58 ± 8.2 years. A total of 32 (44%) patients developed CTRCD during follow-up: 20 (28%) mild CTRCD, 7 (9%) moderate CTRCD, and 5 (7%) severe CTRCD. Cardiac radiation doses were generally higher among patients with CTRCD rather than non-CTRCD. Dose-response relationships were significant for mean CX dose (OR = 2.48, 95%CI (1.12–5.51), p = 0.02) and marginally significant for V2 of LV (OR = 1.03 95%CI (1.00-1.06), p = 0.05). V2 of LV ≥ 36% and mean CX dose ≥ 1.40 Gy thresholds were determined to be optimal for predicting CTRCD. Conclusion For BC patients treated with RT without chemotherapy, CTRCD can be observed in an important proportion of the population over 24 months after treatment. Left ventricle and circumflex coronary artery exposure were found to be associated with CTRCD and could be used for the prediction of such cardiotoxicity. Further research remains needed to confirm these results. Trial Registration ClinicalTrials.gov Identifier- NCT02605512.

Abstract Background The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed to predict extubation outcomes. However, few studies focused on the predicting value of E/Ea and DE at different positions during a spontaneous breathing trial (SBT), as well as the effects of △E/Ea and △DE (changes in E/Ea and DE during a SBT). Methods This study was a reanalysis of the data of 60 difficult-to-wean patients in a previous study published in 2017. All eligible participants were organized into respiratory failure (RF) group and extubation success (ES) group within 48 h after extubation, or re-intubation (RI) group and non-intubation (NI) group within 1 week after extubation. The risk factors for respiratory failure and re-intubation including E/Ea and △E/Ea, DE and △DE at different positions were analyzed by multivariate logistic regression, respectively. The receiver operating characteristic (ROC) curves of E/Ea (septal, lateral, average) and DE (right, left, average) were compared with each other, respectively. Results Of the 60 patients, 29 cases developed respiratory failure within 48 h, and 14 of those cases required re-intubation within 1 week. Multivariate logistic regression showed that E/Ea were all associated with respiratory failure, while only DE (right) and DE (average) after SBT were related to re-intubation. There were no statistic differences among the ROC curves of E/Ea at different positions, nor between the ROC curves of DE. No statistical differences were shown in △E/Ea between RF and ES groups, while △DE (average) was remarkably higher in NI group than that in RI group. However, multivariate logistic regression analysis showed that △DE (average) was not associated with re-intubation. Conclusions E/Ea at different positions during a SBT could predict postextubation respiratory failure with no statistical differences among them. Likewise, only DE (right) and DE (average) after SBT might predict re-intubation with no statistical differences between each other.

BACKGROUND: Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury; however, the specific mechanism is still not clear. Therefore, revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE: To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS: Allen’s impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group. The serum of rats of each group was collected. H9c2 cells were divided into a blank control group, a sham operated rat serum group, a spinal cord injury rat serum group and a luteolin pretreatment group. The cells in blank control group were only cultured with ordinary culture medium. The cells in the sham operated rat serum group were treated with medium containing 10% serum from sham operated rat. The cells in the spinal cord injury rat serum group were treated with medium containing 10% serum from spinal cord injury rat. The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10% rat serum from spinal cord injury rat. After 24 hours of culture, the survival rate of each group of H9c2 cells was measured by CCK-8 assay. Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION: Compared with the blank control group, there was no significant change in cell survival rate in the sham operated rat serum group (P > 0.05). Compared with the sham operated rat serum group, the cell survival rate (P < 0.01) and the expression of LC3 protein (P < 0.05) in spinal cord injury rat serum group was significantly reduced, and the expression of p62 protein was significantly increased (P < 0.05). Compared with the spinal cord injury rat serum group, the survival rate of cells in the luteolin pretreatment group significantly increased (P < 0.000 1); the expression of LC3 protein significantly increased (P < 0.05), and the expression of p62 protein significantly decreased (P < 0.05). The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy. [ABSTRACT FROM AUTHOR]

Purpose: Two-dimensional speckle tracking echocardiography is a novel ultrasound technique, which can detect early subclinical myocardial dysfunction with high sensitivity. The purpose of this study was to explore the value of speckle tracking echocardiography in the evaluation of subclinical myocardial injury in patients with Cushing's syndrome. Methods: 35 patients with Cushing's syndrome and 29 healthy controls matched for age, sex, BMI, and systolic blood pressure were included in the study. All subjects were assessed using both conventional Doppler echocardiography and speckle tracking echocardiography. Among patients, they were further divided into inactive group (n = 7) and active group (n = 28) based on cortisol levels. Trend analysis was used among patients in different disease activity. Correlation analysis and linear regression analysis were used to explore influence factors related to subclinical myocardial dysfunction. Results: Left ventricular ejection fraction value showed no statistical difference between patients Cushing's syndrome and control group. However, GLS and LVSD, show significant differences in Cushing's syndrome group. Also, among active Cushing's syndrome group, inactive Cushing's syndrome group and control group, GLS (−15.4 ± 3.0 vs −18.1 ± 3.1 vs-19.4 ± 2.4, P < 0001) and LVSD (48.9 ± 21.5 vs 43.5 ± 17.9 vs 28.5 ± 8.3, P < 0001) changed significantly with the disease activity status. In addition, GLS and LVSD were both linearly corrected with 24-hour urinary cortisol level. Conclusion: GLS and LVSD are sensitive parameters in detecting and monitoring subclinical myocardial systolic dysfunction in patients with Cushing's syndrome. Myocardial injury is linearly correlated with cortisol level, which can be partially reversed after the biochemical control of cortisol. [ABSTRACT FROM AUTHOR]

Abstract Aims Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. Methods and results In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. Conclusions SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines.

The significance of iron in myocardial mitochondria function cannot be underestimated, because deviations in iron levels within cardiomyocytes may have profound detrimental effects on cardiac function. In this study, we investigated the effects of ferroportin 1 (FPN1) on cardiac iron levels and pathological alterations in mice subjected to chronic intermittent hypoxia (CIH). The cTNT‐FPN1 plasmid was administered via tail vein injection to induce the mouse with FPN1 overexpression in the cardiomyocytes. CIH was established by exposing the mice to cycles of 21%–5% FiO2 for 3 min, 8 h per day. Subsequently, the introduction of hepcidin resulted in a reduction in FPN1 expression, and H9C2 cells were used to establish an IH model to further elucidate the role of FPN1. First, FPN1 overexpression ameliorated CIH‐induced cardiac dysfunction, myocardial hypertrophy, mitochondrial damage and apoptosis. Second, FPN1 overexpression attenuated ROS levels during CIH. In addition, FPN1 overexpression mitigated CIH‐induced cardiac iron accumulation. Moreover, the administration of hepcidin resulted in a reduction in FPN1 levels, further accelerating the CIH‐induced levels of ROS, LIP and apoptosis in H9C2 cells. These findings indicate that the overexpression of FPN1 in cardiomyocytes inhibits CIH‐induced cardiac iron accumulation, subsequently reducing ROS levels and mitigating mitochondrial damage. Conversely, the administration of hepcidin suppressed FPN1 expression and worsened cardiomyocyte iron toxicity injury. [ABSTRACT FROM AUTHOR]

Background: In recent years, the mechanistic interaction between the brain and heart has been explored in detail, which explains the effects of brain injuries on the heart and those of cardiac dysfunction on the brain. Brain injuries are the predominant cause of post-stroke deaths, and cardiac dysfunction is the second leading cause of mortality after stroke onset. Summary: Several studies have reported the association between brain injuries and cardiac dysfunction. Therefore, it is necessary to study the influence on the heart post-stroke to understand the underlying mechanisms of stroke and cardiac dysfunction. This review focuses on the mechanisms and the effects of cardiac dysfunction after the onset of stroke (ischemic or hemorrhagic stroke). Key Messages: The role of the site of stroke and the underlying mechanisms of the brain-heart axis after stroke onset, including the hypothalamic-pituitary-adrenal axis, inflammatory and immune responses, brain-multi-organ axis, are discussed. [ABSTRACT FROM AUTHOR]

Cardiac remodeling is a commonly observed pathophysiological phenomenon associated with the progression of heart failure in various cardiovascular disorders. Carnosol, a phenolic compound extracted from rosemary, possesses noteworthy pharmacological properties including anti‐inflammatory, antioxidant, and anti‐apoptotic activities. Considering the pivotal involvement of inflammation, oxidative stress, and apoptosis in cardiac remodeling, the present study aims to assess the effects of carnosol on cardiac remodeling and elucidate the underlying mechanisms. In an in vivo model, cardiac remodeling was induced by performing transverse aortic constriction (TAC) surgery on mice, while an in vitro model was established by treating neonatal rat cardiomyocytes (NRCMs) with Ang II. Our results revealed that carnosol treatment effectively ameliorated TAC‐induced myocardial hypertrophy and fibrosis, thereby attenuating cardiac dysfunction in mice. Moreover, carnosol improved cardiac electrical remodeling and restored connexin 43 expression, thereby reducing the vulnerability to ventricular fibrillation (VF). Furthermore, carnosol significantly reduced Ang II‐induced cardiomyocyte hypertrophy in NRCMs and alleviated the upregulation of hypertrophy and fibrosis markers. Both in vivo and in vitro models of cardiac remodeling exhibited the anti‐inflammatory, anti‐oxidative, and anti‐apoptotic effects of carnosol. Mechanistically, these effects were mediated through the Sirt1/PI3K/AKT pathway, as the protective effects of carnosol were abrogated upon inhibition of Sirt1 or activation of the PI3K/AKT pathway. In summary, our study suggests that carnosol prevents cardiac structural and electrical remodeling by regulating the anti‐inflammatory, anti‐oxidative, and anti‐apoptotic effects mediated by Sirt1/PI3K/AKT signaling pathways, thereby alleviating heart failure and VF. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage. Our previous studies found that 4-phenylbutyric acid (PBA) was beneficial to septic shock by improving cardiovascular function and survival, while the specific mechanism is unclear. Objectives: We aimed to explore the specific mechanism and PBA for protecting cardiac function in sepsis. Methods: The cecal ligation and puncture-induced septic shock models were used to observe the therapeutic effects of PBA on myocardial contractility and the serum levels of cardiac troponin-T. The mechanisms of PBA against sepsis were explored by metabolomics and network pharmacology. Results: The results showed that PBA alleviated the sepsis-induced cardiac damage. The metabolomics results showed that there were 28 metabolites involving in the therapeutic effects of PBA against sepsis. According to network pharmacology, 11 hub genes were found that were involved in lipid metabolism and amino acid transport following PBA treatment. The further integrated analysis focused on 7 key targets, including Comt, Slc6a4, Maoa, Ppara, Pparg, Ptgs2 and Trpv1, as well as their core metabolites and pathways. In an in vitro assay, PBA effectively inhibited sepsis-induced reductions in Comt, Ptgs2 and Ppara after sepsis. Conclusions: PBA protects sepsis-induced cardiac injury by targeting Comt/Ptgs2/Ppara, which regulates amino acid metabolism and lipid metabolism. The study reveals the complicated mechanisms of PBA against sepsis. [ABSTRACT FROM AUTHOR]

Early detection of cardiac involvement in Juvenile Dermatomyositis (JDM) is difficult due to the absence of clinical signs and symptoms, with systolic dysfunction often emerging in late stages and associated with a poor prognosis. This study aimed to employ two-dimensional speckle-tracking echocardiography (STE) for subclinical assessment of left ventricular (LV) systolic failure in JDM and explore potential associations between impaired LV systolic function (LV-GLS) and disease activity. A prospective study enrolled 20 healthy volunteers and 26 JDM patients (< 18 years old) without cardiac symptoms. Clinical data were collected from medical records, and echocardiograms were conducted by a pediatric cardiologist. Our study cohort demonstrated similar age to controls (13.5 ±.6 vs. 13.8 ± 4.7; p = 0.465). Median illness duration at echocardiography was 5 (1.5–17.5) years, and conventional echocardiography indicated normal LV ejection fraction (> 55%) in all participants. However, STE revealed lowered LV GLS in JDM patients (− 22.2 ± 4.1% vs. − 26.5 ± 5.3% p = 0.022). Pulse steroid users displayed lower GLS average values compared to non-users (β = 4.99, 95% CI 1.34–8.64, p = 0.009). Negative correlations existed between LV-GLS and age at diagnosis (r = − 0.499; p = 0.011), diastolic parameters (E/E′ ratio) and age at diagnosis (r = − 0.469; p = 0.018), as well as RV global strain and age at diagnosis (r = − 0.443; p = 0.024). Employing STE in JDM patients facilitated the identification of preclinical cardiac dysfunction. Given JDM patients' younger age, early myocardial damage detection through STE may impact treatment decisions and long-term cardiovascular prognosis. [ABSTRACT FROM AUTHOR]

Background Corylin, a natural flavonoid, is isolated from the fruit of Psoralea corylifolia L. Nevertheless, the effect of corylin on sepsis-associated cardiac dysfunction is still unclear. The purpose of this study is to determine the role and mechanism of corylin in sepsis related cardiac dysfunction. Methods Experiments were carried out on mice with lipopolysaccharide (LPS) or sepsis induced by cecal ligation and puncture (CLP) or myocardial cell sepsis induced by LPS. Results Administration of corylin improved cardiac dysfunction induced by LPS or CLP in mice. Corylin inhibited the increases of interleukin-1 (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in the heart of mice with LPS or CLP. LPS elevated the levels of IL-1β, IL-6 and TNF-α in cardiomyocytes, which were inhibited by corylin treatment. Corylin attenuated the increases of microRNA (miRNA)-214-5p in the heart of mice with LPS, CLP, LPS-treated NRCMs, H9c2 and AC16 cells. Administration of miRNA-214-5p agomiR reversed the improving effects of corylin on the damaged cardiac function and the increases of IL-1β, IL-6 and TNF-α in mice treated with LPS. Conclusion These outcomes indicated that corylin improved sepsis-associated cardiac dysfunction by inhibiting inflammation. And corylin inhibited inflammation of sepsis by decreasing miRNA-214-5p. Downregulation of miRNA-214-5p improved sepsis-associated cardiac dysfunction and inhibited inflammatory factors. [ABSTRACT FROM AUTHOR]

Aims: Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. Methods and results: In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague‐Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post‐SAH. We determined neuropeptide Y (NPY) 1–5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. Conclusions: SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY–NPY1 receptor pathway, otherwise known as catecholamines. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) has significant systemic manifestations, including cardiovascular morbidity. The main aim of our study was to evaluate the effect of short-term COPD treatment with tiotropium/olodaterol (TIO/OLO) 5/5 μg on cardiac function and autonomic integrity. Methods: Twenty-nine patients with newly diagnosed moderate-to-severe COPD were enrolled. We performed pulmonary function tests, cardiac magnetic resonance, cardiac 123I-metaiodobenzylguanidine (123I-MIBG) imaging and analysis of blood biomarkers on our study subjects. The correlations between the tests' results were evaluated at baseline. The changes in pulmonary and cardiac parameters from baseline through 12 weeks were assessed. Results: Significant associations between pulmonary function tests' results and high-sensitivity C-reactive protein (hs-CRP), as well as interleukin-22 (IL-22), were observed at baseline. Treatment with TIO/OLO significantly improved lung function as measured by spirometry and body plethysmography. Moreover, we found that the cardiac index increased from 2.89 (interquartile range (IQR) 1.09) to 3.21 L/min/m2 (IQR 0.78) (p = 0.013; N = 18) and the late heart-to-mediastinum ratio improved from 1.88 (IQR 0.37) to 2 (IQR 0.41) (p = 0.026; N = 16) after 12 weeks of treatment. Conclusions: Treatment with TIO/OLO improves lung function and positively impacts cardiac function and autonomic integrity, suggesting that dual bronchodilation might have a potential in decreasing the risk for cardiac events in COPD. Hs-CRP and IL-22 might be beneficial in determining the intensity of systemic inflammation in COPD. Further research with a larger cohort is needed to enhance the initial results of this study. [ABSTRACT FROM AUTHOR]

Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca2+-handling abnormalities, mitochondrial Ca2+-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure. [ABSTRACT FROM AUTHOR]

Summary: Iron overload from repeated transfusions has a negative impact on cardiac function, and iron chelation therapy may help prevent cardiac dysfunction in transfusion‐dependent patients with myelodysplastic syndromes (MDS). TELESTO (NCT00940602) was a prospective, placebo‐controlled, randomised study to evaluate the iron chelator deferasirox in patients with low‐ or intermediate‐1–risk MDS and iron overload. Echocardiographic parameters were collected at screening and during treatment. Patients receiving deferasirox experienced a significant decrease in the composite risk of hospitalisation for congestive heart failure (CHF) or worsening of cardiac function (HR = 0.23; 95% CI: 0.05, 0.99; nominal p = 0.0322) versus placebo. No significant differences between the arms were found in left ventricular ejection fraction, ventricular diameter and mass or pulmonary artery pressure. The absolute number of events was low, but the enrolled patients were younger than average for patients with MDS, with no serious cardiac comorbidities and a modest cardiovascular risk profile. These results support the effectiveness of deferasirox in preventing cardiac damage caused by iron overload in this patient population. Identification of patients developing CHF is challenging due to the lack of distinctive echocardiographic features. The treatment of iron overload may be important to prevent cardiac dysfunction in these patients, even those with moderate CHF risk. [ABSTRACT FROM AUTHOR]

AIM: To explore the therapeutic effect of teprenone(geranylgeranylacetone, GGA) on lipopolysaccharide (LPS)-induced cardiac dysfunction and its mechanism. METHODS: (1) Eight-week-old male C57BL/6 wildtype mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein (CHIP) gene knockout mice were randomly divided into control group, LPS group, LPS+GGA group and GGA group, with 8 mice in each group. The model was established by intraperitoneal injection of LPS (25 mg/kg), and 1 h after LPS stimulation, mice were given intraperitoneal injection of GGA (100 mg/kg). The technique of high-resolution ultrasonography system was used to evaluate the cardiac function of mice. The serum of mice from each group were collected to detect the levels of creatine kinase-MB (CKMB) and lactate dehydrogenase (LDH). HE staining was performed to observe histological changes of cardiac tissues. ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in cardiac tissues. Western blot was used to detect the protein levels of HSP70, CHIP, karyopherin-α 2(KPNA2), myeloperoxidase (MPO), vascular cell adhesion molecule (VCAM), intercellular cell adhesion molecule (ICAM), and nuclear factor-κB (NF-κB) in cardiac tissues. (2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS. ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants. Western blot was used to detect the protein expression levels of HSP70, CHIP, and KPNA2 in myocardial cells. Immunofluorescence staining was performed to observe the content of nuclear NF- κB. RESULTS: (1) GGA effectively improved cardiac function of LPS-stimulated mice, significantly increased ejection fraction and left ventricular fractional shortening (P<0. 01), reduced serum levels of CK-MB and LDH (P<0. 01), and alleviated myocardial injury. (2) GGA significantly reduced the release of TNF-α and IL-6 caused by LPS (P<0. 01), as well as nuclear translocation of NF-κB, decreased the levels of KPNA2, MPO, VCAM and ICAM in cardiac tissues, and increased the levels of HSP70 in cardiac tissues and cells (P<0. 01). (3) In CHIP knockout myocardial cells and mice, GGA failed to inhibit LPS-induced inflammatory response and lost its effect on improving cardiac function. CONCLUSION: The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation, which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release. CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury. [ABSTRACT FROM AUTHOR]

Recent studies have found increased cardiovascular mortality risk in patients with type 1 diabetes when compared to normoglycemic people, even when they were kept under good glycemic control. However, the mechanisms underlying this condition have yet to be fully understood. Using streptozotocin (STZ)-induced diabetic rats, we evaluated the effects of insulin replacement therapy on cardiac, autonomic, inflammatory, and oxidative stress parameters. Daily treatment with insulin administrated subcutaneously in the STZ-diabetic rats showed a reduction in hyperglycemia (>250 mg/dL) to normalized values. The insulin treatment was effective in preventing alterations in cardiac morphometry and systolic function but had no impact on diastolic function. Also, the treatment was not able to prevent the impairment of baroreflex-tachycardic response and systolic arterial pressure variability (SAP-V). A correlation was found between improvement of these autonomic parameters and higher levels of IL-10 and lower levels of oxidized glutathione. Our findings show that insulin treatment was not able to prevent diastolic, baroreflex, and SAP-V dysfunction, suggesting an outstanding cardiovascular risk, even after obtaining a good glycemic control in STZ-induced diabetic rats. This study shed light on a relatively large population of diabetic patients in need of other therapies to be used in combination with insulin treatment and thus more effectively manage cardiovascular risk. [ABSTRACT FROM AUTHOR]

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles. [ABSTRACT FROM AUTHOR]

More than 26 million people in the world suffer from heart failure and heart dysfunction. Examination of patients with both diseases, especially in the deceased, is very difficult due to lack of medical records, limitations of clinical examination and morphological changes that are not visible to the naked eye. Today, BNP and NT-proBNP have been widely used as significant indicators for the diagnosis of heart failure and cardiac dysfunction, both in clinical and forensic fields, and numerous studies have examined the usefulness of BNP and NT-proBNP from all sides in clinical and forensic fields. The purpose of this article is to discuss biological features, current research related to their applications and future research prospects of BNP and NT-proBNP in clinical and forensic fields. The method used in this study is a literature study, by collecting and analyzing relevant literature related to the role of BNP and NT-proBNP in the diagnosis, therapy, and prognosis of heart disease. BNP and NT-proBNP are important biomarkers in clinical and forensic fields for heart disease assessment. With technological developments in the field of molecular biology, it is expected that the use of BNP and NT-proBNP can become more precise and accurate in the future, improving diagnosis, treatment, and understanding of heart disease in both living and post-mortem patients. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are a class of illnesses that affect the heart or blood vessels, leading to the most common causes of death worldwide. In 2017, CVD caused approximately 17.8 million deaths that were increased approximately to 20.5 million deaths in 2021, globally. Also, nearly 80% of worldwide CVD deaths occur in some countries. Some herbs and their constituents due to their several pharmacological activities have been used for medicinal purposes. Carvacrol is a phenolic mono‐terpenoid found in the oils of aromatic herbs with several biological properties. The possible therapeutic effects of carvacrol on lipid profiles, oxidative stress, hypertension, and cardiac dysfunction were summarized in the current study. The data from this review article were obtained by searching the terms including; "Carvacrol", "Hypertension", Hypotensive, "Cardiac dysfunction", "Ischemia", "Lipid profile", and Oxidative stress in several web databases such as Web of Sciences, PubMed Central, and Google Scholar, until November 2023. The results of the reviewed studies revealed that carvacrol inhibits acetylcholinesterase (AchE) activity and alters lipid profiles, reducing heart rate as well as systolic and diastolic blood pressure (BP). Carvacrol also decreased the proinflammatory cytokine (IL‐1β), while increasing secretion of anti‐inflammatory cytokine (IL‐10). Moreover, carvacrol improved oxidative stress and mitigated the number of apoptotic cells. The pharmacological effects of carvacrol on CVD might be through its antioxidative, anti‐inflammatory, and antiapoptotic effects. The mentioned therapeutic effects of carvacrol on lipid profile, hypertension, and cardiac dysfunction indicate the possible remedy effect of carvacrol for the treatment of CVD. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors (CCSs) face an increased risk of cardiovascular disease (CVD). This systematic review aims to provide the first synthesis of observational and interventional studies on the relationship between diet and cardiovascular health in CCSs. Methods: A comprehensive search was conducted for studies published between 1990 and July 2023 in PubMed, MEDLINE, CINAHL, Child Development & Adolescent Studies, and Cochrane Library. Eligible studies included observational and interventional studies examining the associations or effects of dietary factors on CVD incidence, cardiac dysfunction, or CVD risk factors in CCSs diagnosed before age 25 years. Results: Ten studies met the inclusion criteria (nine observational and one interventional). Collectively, they comprised 3485 CCSs (male, 1734; female, 1751). The outcomes examined across observational studies included characteristics of obesity, diabetes biomarkers, hypertension indicators, dyslipidaemia biomarkers, and metabolic syndrome. The evidence suggested that greater adherence to healthy diets was associated with lower body mass index, blood pressure, glucose, and triglycerides and higher high-density lipoprotein cholesterol. The 12-week lifestyle intervention study in childhood leukaemia survivors found no impact on obesity indicators. Conclusion: The review results indicate the potentially protective effects of healthy diets. However, the available research remains preliminary and limited, underscoring the need for more rigorous, adequately powered studies. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular diseases (CVDs) that has become a global public health problem. Puerarin (PUE), the principal active compound of Pueraria lobata, has the effects of regulating glucose and lipid metabolism and protecting against cardiovascular damage. This study aimed to investigate whether dietary supplementation with PUE could ameliorate MetS and its associated cardiovascular damage. Rats were randomly divided into three groups: the normal diet group (NC), the high-fat/high-sucrose diet group (HFHS), and the HFHS plus PUE diet group (HFHS-PUE). The results showed that PUE-supplemented rats exhibited enhanced glucose tolerance, improved lipid parameters, and reduced blood pressure compared to those on the HFHS diet alone. Additionally, PUE reversed the HFHS-induced elevations in the atherogenic index (AI) and the activities of serum lactate dehydrogenase (LDH) and creatine kinase (CK). Ultrasonic evaluations indicated that PUE significantly ameliorated cardiac dysfunction and arterial stiffness. Histopathological assessments further confirmed that PUE significantly mitigated cardiac remodeling, arterial remodeling, and neuronal damage in the brain. Moreover, PUE lowered systemic inflammatory indices including C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). In conclusion, dietary supplementation with PUE effectively moderated metabolic disorders, attenuated systemic inflammation, and minimized cardiovascular damage in rats with MetS induced by an HFHS diet. These results provide novel insights into the potential benefits of dietary PUE supplementation for the prevention and management of MetS and its related CVDs. [ABSTRACT FROM AUTHOR]

Background Septic shock is associated with increases in end‐diastolic volume (EDV) and decreases in ejection fraction that reverse within 10 days. Nonsurvivors do not develop EDV increases. The mechanism is unknown. Methods and Results Purpose‐bred beagles (n=33) were randomized to receive intrabronchial Staphylococcus aureus or saline. Over 96 hours, cardiac magnetic resonance imaging and echocardiograms were performed. Tissue was obtained at 66 hours. From 0 to 96 hours after bacterial challenge, septic animals versus controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%). On histology, the major finding was nonocclusive microvascular injury with edema in myocytes, the interstitium, and endothelial cells. Edema was associated with significant worsening of biventricular ejection fractions, ventricular‐arterial coupling, and circumferential strain. Early during sepsis, (0–24 hours), the EDV decreased; significantly more in nonsurvivors (ie, greater diastolic dysfunction). From 24 to 48 hours, septic animals' biventricular chamber sizes increased; in survivors significantly greater than baseline and nonsurvivors, whose EDVs were not different from baseline. Preload, afterload, or heart rate differences did not explain these differential changes. Conclusions The cardiac dysfunction of sepsis is associated with wall edema. In nonsurvivors, at 0 to 24 hours, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part, explain the EDV increases from 24 to 48 hours because of a potentially reparative process removing damaged wall tissue. Septic cardiomyopathy is most consistent with a nonocclusive microvascular injury resulting in edema causing reversible systolic and diastolic dysfunction with more severe diastolic dysfunction being associated with a decreased EDV and death.

Objective: Obesity increases deposition of extracellular matrix (ECM) components of cardiac tissue. Since obesity aggregates with insulin resistance and heart disease, it is imperative to determine whether the increased ECM deposition contributes to this disease cluster. The hypotheses tested in this study were that in cardiac tissue of obese mice i) increased deposition of ECM components (collagens and hyaluronan) contributes to cardiac insulin resistance and that a reduction in these components improves cardiac insulin action and ii) reducing excess collagens and hyaluronan mitigates obesity-associated cardiac dysfunction. Methods: Genetic and pharmacological approaches that manipulated collagen and hyaluronan contents were employed in obese C57BL/6 mice fed a high fat (HF) diet. Cardiac insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp and cardiac function was measured by pressure-volume loop analysis in vivo. Results: We demonstrated a tight association between increased ECM deposition with cardiac insulin resistance. Increased collagen deposition by genetic deletion of matrix metalloproteinase 9 (MMP9) exacerbated cardiac insulin resistance and pirfenidone, a clinically available anti-fibrotic medication which inhibits collagen expression, improved cardiac insulin resistance in obese mice. Furthermore, decreased hyaluronan deposition by treatment with PEGylated human recombinant hyaluronidase PH20 (PEGPH20) improved cardiac insulin resistance in obese mice. These relationships corresponded to functional changes in the heart. Both PEGPH20 and pirfenidone treatment in obese mice ameliorated HF diet-induced abnormal myocardial remodelling. Conclusion: Our results provide important new insights into the role of ECM deposition in the pathogenesis of cardiac insulin resistance and associated dysfunction in obesity of distinct mouse models. These findings support the novel therapeutic potential of targeting early cardiac ECM abnormalities in the prevention and treatment of obesity-related cardiovascular complications.