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In this review paper, we search the recent literature regarding the application of the heart-brain interaction theories in the field of intensive care unit. Simultaneously, we methodically summarize the clinical evidence supporting its application in intensive care unit treatment, based on clinical randomized trials and clinical case studies. We delve into how it's applied in treating severely ill patients and in researching animal models for cardio-cerebral comorbidities, aiming to supply benchmarks for subsequent clinical trials and studies on mechanisms.

Neuroinflammation caused by microglia in the central nervous system (CNS) is observed after myocardial infarction (MI). However, the inflammatory response mechanism remains unclear. BuChang Naoxintong capsule (NXT) is a Chinese medicine for treating ischemic cardio-cerebrovascular diseases, requiring more studies to understand the pharmacodynamic mechanism. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in rats. Additionally, histopathological staining in the left ventricular (LV) and immunofluorescence within the brain cortex after 1 d and 7 d of MI were performed to determine the NXT pharmacodynamic action and best administration dosage. Proteomics helped obtain the essential proteins related to neuroinflammation and MI in the heart and brain tissue after 7 d of MI. Based on TTC, HE, Masson, and immunofluorescence staining results of CD206 and IBA-1, NXT demonstrated a better pharmacodynamic action towards myocardial injury and neuroinflammation after 7 d of MI. Moreover, the human equivalent dosage of NXT (220 mg/kg) became the best administration dose. The proteome bioinformatics analysis in the LV and brain cortex was performed. Thus, the elongation of very long-chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) became critical proteins related to MI and neuroinflammation. The western blotting results indicated that ABCG4 expression possessed the same trend as the proteomics results. The auto-dock results revealed that ABCG4 had a good binding ability with Ferulic acid, Paeoniflorin, and Tanshinone II A, the key ingredients of NXT. The cellular thermal shift assay results demonstrated that ABCG4 showed better thermal stability post-NXT treatment. NXT can improve myocardial injury, such as heart infarct size, pathological injury, myocardial fibrosis, and inflammatory cell infiltration. Additionally, brain neuroinflammation induced by microglia after MI affects the expression and structure of ABCG4. Thus, ABCG4 could be the key protein associated with MI and neuroinflammation. [ABSTRACT FROM AUTHOR]

Abstract Myocardial infarction (MI) induces neuroinflammation indirectly, chronic neuroinflammation may cause neurodegenerative diseases. Changes in the proteomics of heart and brain tissue after MI may shed new light on the mechanisms involved in neuroinflammation. This study explored brain and heart protein changes after MI with a data-independent acquisition (DIA) mode proteomics approach. Permanent ligation of the left anterior descending coronary artery (LAD) was performed in the heart of rats, and the immunofluorescence of microglia in the brain cortex was performed at 1d, 3d, 5d, and 7d after MI to detect the neuroinflammation. Then proteomics was accomplished to obtain the vital proteins in the heart and brain post-MI. The results show that the number of microglia was significantly increased in the Model-1d group, the Model-3d group, the Model-5d group, and the Model-7d group compared to the Sham group. Various proteins were obtained through DIA proteomics. Linking to key targets of brain disease, 14 proteins were obtained in the brain cortex. Among them, elongation of very long chain fatty acids protein 5 (ELOVL5) and ATP-binding cassette subfamily G member 4 (ABCG4) were verified through western blotting (WB). The results of WB were consistent with the proteomics results. Therefore, these proteins may be related to the pathogenesis of neuroinflammation after MI.

Diagnosis and treatment of patients with cardiovascular and neurologic diseases primarily focus on the heart and brain, respectively. An increasing number of preclinical and clinical studies have confirmed a causal relationship between heart and brain diseases. Cardiogenic dementia is a cognitive impairment caused by heart dysfunction and has received increasing research attention. The prevention and treatment of cardiogenic dementia are essential to improve the quality of life, particularly in the elderly and aging population. This study describes the changes in cognitive function associated with coronary artery disease, myocardial infarction, heart failure, atrial fibrillation and heart valve disease. An updated understanding of the two known pathogenic mechanisms of cardiogenic dementia is presented and discussed. One is a cascade of events caused by cerebral hypoperfusion due to long-term reduction of cardiac output after heart disease, and the other is cognitive impairment regardless of the changes in cerebral blood flow after cardiac injury. Furthermore, potential medications for the prevention and treatment of cardiogenic dementia are reviewed, with particular attention to multicomponent herbal medicines.

Ethnopharmacological Relevance: Ischemic stroke (IS) is a major cause of mortality. Inflammation exerts an essential part of brain-heart communication after IS. Naoxintong capsule (NXT), derived from the classical Traditional Chinese Medicine (TCM) formulation Bu-Yang-Huan-Wu-Tang, are extensively employed in China to manage IS, myocardial infarction (MI), and atherosclerosis. Previous clinical studies have demonstrated the protective effects of NXT in anti-atherosclerosis, cerebral infarction, angina, and acute coronary syndrome. However, the potential therapeutic mechanism of NXT for IS remains unknown., Aim of the Study: This study aims to investigate a potential mechanism for enhancing brain-heart interaction following an ischemic stroke., Materials and Methods: C57BL/6J mice underwent permanent middle cerebral artery occlusion (MCAO) for durations of 6, 12, and 24 h. The effects of NXT on the brain were observed via TTC, Nissl and TUNEL staining, immunofluorescence staining, and Zea-Longa scores. Simultaneously, the effects of NXT on the heart were evaluated via H&E staining and echocardiography. Inflammatory factors in heart and serum were determined via ELISA or luminex liquid suspension chip detection. Network pharmacology predicted the targets and signaling pathways of NXT. The binding affinity between potential targets and active compounds of NXT was assessed through molecular docking. The expression levels of IκBα, IKKβ, NF-κB, NLRP3, and caspase-1 were evaluated via Western blotting., Results: The Zea-Longa scores, infarct rate, and the rate of apoptosis in the brain at 6, 12, and 24 h of MCAO mice were markedly decreased by NXT. Additionally, they clearly enhanced the NeuN positive rate and prevented microglia from activating at 24 h. NXT significantly reduced the level of myocardial injury biomarkers (Lactate dehydrogenase (LDH) and Creatine kinase isoenzyme MB (CK-MB) at 24 h, N-terminal pro-brain natriuretic peptide (NT-pro BNP) at 6, 12, and 24 h), improved ejection fraction, fractional shortening, stroke volume, and cardiac output at 24 h. The levels of MIP-1α in cardiac tissue and IL-1β in serum were both markedly lowered by NXT. Furthermore, the NF-κB/NLRP3/caspase-1 signaling pathways may be potential mechanisms of NXT. Molecular docking indicated that IKKβ, IκBα, NF-κB, NLRP3, and caspase-1 may serve as potential targets for the action of representative active ingredients in NXT. NXT could reduce the expression levels of IKKβ, NF-κB, NLRP3, and caspase-1 in brain and heart tissues while increasing the expression of IκBα., Conclusions: Our study illustrates that NXT efficiently attenuated inflammation in the brain and heart by blocking the NF-κB/NLRP3/caspase-1 signaling pathway. These findings provide appealing insights into the multi-organ perspective on human health via identifying shared inflammatory impacts and heart-brain linkages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In this review paper, we search the recent literature regarding the application of the heart-brain interaction theories in the field of intensive care unit. Simultaneously, we methodically summarize the clinical evidence supporting its application in intensive care unit treatment, based on clinical randomized trials and clinical case studies. We delve into how it's applied in treating severely ill patients and in researching animal models for cardio-cerebral comorbidities, aiming to supply benchmarks for subsequent clinical trials and studies on mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Qi, Wang, Liu, Hua, Yang and Liu.)

Sleep is essential to the normal psychological and physiological activities of the human body. Increasing evidence indicates that sleep deprivation is associated with the occurrence, development, and poor treatment effects of various arrhythmias. Sleep deprivation affects not only the peripheral nervous system but also the central nervous system, which regulates the occurrence of arrhythmias. In addition, sleep deprivation is associated with apoptotic pathways, mitochondrial energy metabolism disorders, and immune system dysfunction. Although studies increasingly suggest that pathological sleep patterns are associated with various atrial and ventricular arrhythmias, further research is needed to identify specific mechanisms and recommend therapeutic interventions. This review summarizes the findings of sleep deprivation in animal experiments and clinical studies, current challenges, and future research directions in the field of arrhythmias. [ABSTRACT FROM AUTHOR]

Neuroscientists have emphasized visceral influences on consciousness and attention, but the potential neurophysiological pathways remain under exploration. Here, we found two neurophysiological pathways of heart-brain interaction based on the relationship between oxygen-transport by red blood cells (RBCs) and consciousness/attention. To this end, we collected a dataset based on the routine physical examination, the breaking continuous flash suppression (b-CFS) paradigm, and an attention network test (ANT) in 140 immigrants under the hypoxic Tibetan environment. We combined electroencephalography and multilevel mediation analysis to investigate the relationship between RBC properties and consciousness/attention. The results showed that RBC function, via two independent neurophysiological pathways, not only triggered interoceptive re-representations in the insula and awareness connected to orienting attention but also induced an immune response corresponding to consciousness and executive control. Importantly, consciousness played a fundamental role in executive function which might be associated with the level of perceived stress. These results indicated the important role of oxygen-transport in heart-brain interactions, in which the related stress response affected consciousness and executive control. The findings provide new insights into the neurophysiological schema of heart-brain interactions. [ABSTRACT FROM AUTHOR]

An increasing number of evidence suggests that bidirectional communication between the cardiovascular system and the central nervous system (CNS), known as the heart-brain interaction, is crucial in understanding the impact of coronary artery disease (CAD) on brain health. The multifactorial role of CAD in the brain involves processes such as inflammation, oxidative stress, neuronal activity, neuroendocrine imbalances, and reduced cerebral perfusion, leading to various cerebral abnormalities. The mechanisms underlying the relationship between CAD and brain injury are complex and involve parallel pathways in the CNS, endocrine system, and immune system. Although the exact mechanisms remain partially understood, neuroimaging techniques offer valuable insights into subtle cerebral abnormalities in CAD patients. Neuroimaging techniques, including assessment of neural function, brain metabolism, white matter microstructure, and brain volume, provide information on the evolving nature of CAD-related cerebral abnormalities over time. This review provides an overview of the pathophysiological mechanisms of CAD in the heart-brain interaction and summarizes recent neuroimaging studies utilizing multiparametric techniques to investigate brain abnormalities associated with CAD. The application of advanced neuroimaging, particularly functional, diffusion, and perfusion advanced techniques, offers high resolution, multiparametric capabilities, and high contrast, thereby allowing for the early detection of changes in brain structure and function, facilitating further exploration of the intricate relationship between CAD and brain health. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3., (© 2024 International Society for Magnetic Resonance in Medicine.)

The brain continuously receives input from the internal and external environment. Using this information, the brain exerts its influence on both itself and the body to facilitate an appropriate response. The dynamic interplay between the brain and the heart and how external conditions modulate this relationship deserves attention. In high-stress situations, synchrony between various brain regions such as the prefrontal cortex and the heart may alter. This flexibility is believed to facilitate transitions between functional states related to cognitive, emotional, and especially autonomic activity. This study examined the dynamic temporal functional association of heart rate variability (HRV) with the interaction between three main canonical brain networks in 38 healthy male subjects at rest and directly after a psychosocial stress task. A sliding window approach was used to estimate the functional connectivity (FC) among the salience network (SN), central executive network (CEN), and default mode network (DMN) in 60-s windows on time series of blood-oxygen-level dependent (BOLD) signal. FC between brain networks was calculated by Pearson correlation. A multilevel linear mixed model was conducted to examine the window-by-window association between the root mean square of successive differences between normal heartbeats (RMSSD) and FC of network-pairs across sessions. Our findings showed that the minute-by-minute correlation between the FC and RMSSD was significantly stronger between DMN and CEN than for SN and CEN in the baseline session [b = 4.36, t(5025) = 3.20, p = 0.006]. Additionally, this differential relationship between network pairs and RMSSD disappeared after the stress task; FC between DMN and CEN showed a weaker correlation with RMSSD in comparison to baseline [b = −3.35, t(5025) = −3.47, p = 0.006]. These results suggest a dynamic functional interplay between HRV and the functional association between brain networks that varies depending on the needs created by changing conditions.

The brain continuously receives input from the internal and external environment. Using this information, the brain exerts its influence on both itself and the body to facilitate an appropriate response. The dynamic interplay between the brain and the heart and how external conditions modulate this relationship deserves attention. In high-stress situations, synchrony between various brain regions such as the prefrontal cortex and the heart may alter. This flexibility is believed to facilitate transitions between functional states related to cognitive, emotional, and especially autonomic activity. This study examined the dynamic temporal functional association of heart rate variability (HRV) with the interaction between three main canonical brain networks in 38 healthy male subjects at rest and directly after a psychosocial stress task. A sliding window approach was used to estimate the functional connectivity (FC) among the salience network (SN), central executive network (CEN), and default mode network (DMN) in 60-s windows on time series of blood-oxygen-level dependent (BOLD) signal. FC between brain networks was calculated by Pearson correlation. A multilevel linear mixed model was conducted to examine the window-by-window association between the root mean square of successive differences between normal heartbeats (RMSSD) and FC of network-pairs across sessions. Our findings showed that the minute-by-minute correlation between the FC and RMSSD was significantly stronger between DMN and CEN than for SN and CEN in the baseline session [ b = 4.36, t (5025) = 3.20, p = 0.006]. Additionally, this differential relationship between network pairs and RMSSD disappeared after the stress task; FC between DMN and CEN showed a weaker correlation with RMSSD in comparison to baseline [ b = −3.35, t (5025) = −3.47, p = 0.006]. These results suggest a dynamic functional interplay between HRV and the functional association between brain networks that varies depending on the needs created by changing conditions. [ABSTRACT FROM AUTHOR]

Diagnosis and treatment of patients with cardiovascular and neurologic diseases primarily focus on the heart and brain, respectively. An increasing number of preclinical and clinical studies have confirmed a causal relationship between heart and brain diseases. Cardiogenic dementia is a cognitive impairment caused by heart dysfunction and has received increasing research attention. The prevention and treatment of cardiogenic dementia are essential to improve the quality of life, particularly in the elderly and aging population. This study describes the changes in cognitive function associated with coronary artery disease, myocardial infarction, heart failure, atrial fibrillation and heart valve disease. An updated understanding of the two known pathogenic mechanisms of cardiogenic dementia is presented and discussed. One is a cascade of events caused by cerebral hypoperfusion due to long-term reduction of cardiac output after heart disease, and the other is cognitive impairment regardless of the changes in cerebral blood flow after cardiac injury. Furthermore, potential medications for the prevention and treatment of cardiogenic dementia are reviewed, with particular attention to multicomponent herbal medicines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Liu, Xiao, Liang, He, Lyu and Zhu.)

While for a long time in human history it was assumed that the heart was important for emotional and cognitive functions, in today's "rational" world the role of the heart is often reduced to its function as a pump that supplies the body with blood. However, more and more studies are showing that the heart actually contributes to daily cognitive and emotional functions. Evidence is accumulating that much of cognition and emotion - perhaps all - represent integrated (body) cardioneural states and as such are constantly dependent on an intact heart-brain interaction (HBI). I will show how even simple perceptual tasks are dependent on HBI and also on breathing. It follows that any disturbance of the HBI will alter our emotions and cognition. Such disturbances can be caused, for example, by medication and recreational drugs. Long-term and/or repeated psychosocial stress can also have a negative impact on HBI. In particular, I will outline how long-term changes in HBI could be of great importance for the development of cardiovascular diseases such as hypertension and cardiac arrhythmias, as well as mental disorders such as anxiety and depression. [ABSTRACT FROM AUTHOR]

Some of the most important integrative control centers for the autonomic nervous system are located in the brainstem and the hypothalamus. However, growing recent neuroimaging evidence support that a set of cortical regions, named the central autonomic network (CAN), is involved in autonomic control and seems to play a major role in continuous autonomic cardiac adjustments to high-level emotional, cognitive or sensorimotor cortical activities. Intracranial explorations during stereo-electroencephalography (SEEG) offer a unique opportunity to address the question of the brain regions involved in heart-brain interaction, by studying: (i) direct cardiac effects produced by the electrical stimulation of specific brain areas; (ii) epileptic seizures inducing cardiac modifications; (iii) cortical regions involved in cardiac interoception and source of cardiac evoked potentials. In this review, we detail the available data assessing cardiac central autonomic regulation using SEEG, address the strengths and also the limitations of this technique in this context, and discuss perspectives. The main cortical regions that emerge from SEEG studies as being involved in cardiac autonomic control are the insula and regions belonging to the limbic system: the amygdala, the hippocampus, and the anterior and mid-cingulate. Although many questions remain, SEEG studies have already demonstrated afferent and efferent interactions between the CAN and the heart. Future studies in SEEG should integrate these afferent and efferent dimensions as well as their interaction with other cortical networks to better understand the functional heart-brain interaction. [ABSTRACT FROM AUTHOR]

Background: Early repolarization pattern (ER) gained attention as a risk factor for ventricular arrhythmia and sudden cardiac death in the general population. While electrocardiographic abnormalities are frequent findings in stroke patients, data on ER pattern in this population are lacking. Methods: We assessed the prevalence of ER pattern in consecutive acute stroke patients at a tertiary stroke center. Functional outcome after 90 days was analyzed to determine the effect of an ER pattern on mortality. Multivariate logistic regression analysis was used to identify factors associated with an ER pattern. Results: Out of 1141 consecutive stroke patients 771 patients remained for analysis after application of exclusion criteria. ER was observed in 62 (8.04 %) patients. ER was more prevalent among subjects with intracerebral and subarachnoidal hemorrhage (13.0 %) than among patients with ischemic stroke (7.0 %; p = 0.024). Multiple regression analysis revealed QRS-duration (OR 0.972 95 % CI 0.950-0.994, p = 0.012), QT-duration (OR 1.009, 95 % CI 1.004-1.014, p = 0.001) and mechanical ventilation on admission (OR 0.320, 95 % CI 0.136-0.752, p = 0.009) as independent predictors for ER. Overall ER on admission was not associated with increased mortality at 3-month follow-up (ER 11.3 % vs. non-ER 9.2 %; p = 0.582). Conclusions: ER is frequently found among patients with acute cerebrovascular events and is more prevalent in patients with hemorrhagic compared to ischemic events. Our study yields no evidence that ER is associated with worse outcome or mortality after stroke. [ABSTRACT FROM AUTHOR]

• Statistical modelling of brain-heart interaction by including prior cardiac physiological knowledge. • Biophysical modelling constrained by a model of joint heart-brain variability. • The model identifies physiologically plausible mechanisms and significant differences associated to clinical conditions. • We present the first study on patient-specific modelling relating cardiac function and brain damage. • This study is based on the largest presented cohort of personalised subjects to date (3445 individuals). [Display omitted] Initiatives such as the UK Biobank provide joint cardiac and brain imaging information for thousands of individuals, representing a unique opportunity to study the relationship between heart and brain. Most of research on large multimodal databases has been focusing on studying the associations among the available measurements by means of univariate and multivariate association models. However, these approaches do not provide insights about the underlying mechanisms and are often hampered by the lack of prior knowledge on the physiological relationships between measurements. For instance, important indices of the cardiovascular function, such as cardiac contractility, cannot be measured in-vivo. While these non-observable parameters can be estimated by means of biophysical models, their personalisation is generally an ill-posed problem, often lacking critical data and only applied to small datasets. Therefore, to jointly study brain and heart, we propose an approach in which the parameter personalisation of a lumped cardiovascular model is constrained by the statistical relationships observed between model parameters and brain-volumetric indices extracted from imaging, i.e. ventricles or white matter hyperintensities volumes, and clinical information such as age or body surface area. We explored the plausibility of the learnt relationships by inferring the model parameters conditioned on the absence of part of the target clinical features, applying this framework in a cohort of more than 3 000 subjects and in a pathological subgroup of 59 subjects diagnosed with atrial fibrillation. Our results demonstrate the impact of such external features in the cardiovascular model personalisation by learning more informative parameter-space constraints. Moreover, physiologically plausible mechanisms are captured through these personalised models as well as significant differences associated to specific clinical conditions. [ABSTRACT FROM AUTHOR]

• The conditional entropy technique enabled simultaneous analysis of heart-brain rhythms. • Directional coupling information C (heart→brain) and C (brain→heart) differentiated internally and externally operative attention. • Attention states were examined using simultaneous recording of EEG and ECG signals. • A modified Posner's spatial orienting task used to assess A I and A E attention. • Internal and external attention states investigated using identical stimulus design. Heart and brain interactions mediate human cognition. This investigation identifies heart-brain interactions during internally operative attention (A I) and externally operative attention (A E). A I attention involves short term memory, whereas A E attention deals with automatic and transient response to objects in the external world. A modified Posner's spatial orienting task used to differentiate A I and A E attention. Heart and brain rhythms recorded in fourteen healthy participants. Functional coupling from heart-to-brain (C h e a r t → b r a i n) and brain-to-heart (C b r a i n → h e a r t) time series derived using an information domain approach based on conditional entropy. The experimental results showed that low-frequency power of heart rate variability (HRV-LF) and sympathovagal balance (LF/HF ratio) during A E significantly increased compared with that for A I. Furthermore, the information flow from heart-to-brain increased and decreased form brain-to-heart during A E as compared to A I. Also, opposite trend in relationship noted between coupling index (C i → j) and HRV-LF during A I and A E attention. The conditional entropy technique enabled simultaneous analysis of heart-brain rhythms to identify heart-brain interactions during A I and A E attention. [ABSTRACT FROM AUTHOR]

Humans are increasingly aware that their fate will depend on the wisdom they apply in interacting with the ecosystem. Its health is defined as the condition in which the ecosystem can deliver and continuously renew its fundamental services. A healthy ecosystem allows optimal interactions between humans and the other biotic/abiotic components, and only in a healthy ecosystem can humans survive and efficiently reproduce. Thus, both the human and ecosystem health should be considered together in view of their interdependence. The present article suggests that this relationship could be considered starting from the Hippocrates (460 BC-370 BC) work "On Airs, Waters, and Places" to derive useful medical and philosophical implications for medicine which is indeed a topic that involves scientific as well as philosophical concepts that implicate a background broader than the human body. The brain-body-ecosystem medicine is proposed as a new more complete approach to safeguarding human health. Epidemiological data demonstrate that exploitation of the environment resulting in ecosystem damage affects human health and in several instances these diseases can be detected by modifications in the heart-brain interactions that can be diagnosed through the analysis of changes in heart rate variability., Competing Interests: The authors declare no conflict of interest.

This work reports the results of an evaluation study to assess the efficacy of the Early HeartSmarts (EHS) program in schools of the Salt Lake City, Utah, School District. The EHS program is designed to guide teachers with methods that support young children (3-6 y old) in learning emotion self-regulation and key age-appropriate socioemotional competencies with the goal of facilitating their emotional, social, and cognitive development. The study was conducted over one school year using a quasiexperimental longitudinal field research design with 3 measurement points (baseline, preintervention, and postintervention) using The Creative Curriculum Assessment (TCCA), a teacher-scored, 50-item instrument measuring students growth in 4 areas of development: social/emotional, physical, cognitive, and language development. Children in 19 preschool classrooms in the Salt Lake City School District were divided into intervention and control group samples (n = 66 and n = 309, respectively; mean age = 3.6 y). The intervention classes were specifically selected to target children of lower socioeconomic and ethnic minority backgrounds. Overall, there is compelling evidence of the efficacy of the EHS program in increasing total psychosocial development and each of the 4 development areas measured by the TCCA: the results of a series of analyses of covariance found a strong, consistent pattern of large, significant differences on the development measures favoring preschool children who received the EHS program over those in the control group.