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Clinical and experimental observations prove that heparin-neutralizing doses of protamine increase pulmonary artery pressures and decrease systemic BP. Protamine also increases myocardial oxygen consumption, cardiac output, and heart rate, and decreases systemic vascular resistance. These cardiovascular effects have clinical consequences that have justified studies in this area. Protamine adverse reactions usually have three different categories: systemic hypotension, anaphylactoid reactions, and catastrophic pulmonary vasoconstriction. The precise mechanism that explains protamine-mediated systemic hypotension is unknown. Four experimental protocols performed at Mayo Clinic, Rochester, MN, studied the intrinsic mechanism of protamine vasodilation. The first study reported in vitro systemic and coronary vasodilation after protamine infusion. The second in vitro study suggested that the pulmonary circulation is extensively involved in the protamine-mediated effects on endothelial function. The third study, carried out in anesthetized dogs, reported the methylene blue and nitric oxide synthase blockers neutralization of the protamine vasodilatatory effects. The fourth study suggested that protamine also causes endothelium-dependent vasodilation in heart microvessels and conductance arteries by different mechanisms including hyperpolarization. Reviewing these experimental results and our clinical experience, we suggest methylene blue as a novel approach to prevent and treat hemodynamic complications caused by the use of protamine after cardiopulmonary bypass. In the absence of prospective clinical trials, a growing body of cumulative clinical evidence suggests that methylene blue may be strongly considered as a therapeutic approach in the treatment of distributive shock. [ABSTRACT FROM AUTHOR]

Introduction: Hemorrhagic shock requires immediate treatment to prevent mortality and organ dysfunction. This study evaluates the efficacy of methylene blue (MB) with blood transfusion (BT) as a potential rescue therapy in acute severe bleeding in pigs., Methods: Thirty animals were randomly assigned to one of six groups following the induction of fixed-pressure hemorrhagic shock, after reaching a mean arterial pressure (MAP) of 55 mmHg - Group 1 (60 BT: BT after 60 minutes), Group 2 (60 MB: MB infusion after 60 minutes), Group 3 (60 MB + BT: MB and BT after 60 minutes), Group 4 (15 MB + BT: MB and BT after 15 minutes), Group 5 (15 BT + 60 MB: BT after 15 minutes and MB infusion after 60 minutes), and Group 6 (15 MB + 60 BT: MB infusion after 15 minutes and BT after 60 minutes). Hemodynamic and blood gas parameters were meticulously recorded, reversal of the shock was considered when MAP reached 90% of the baseline MAP., Results: Except for Group 2, all groups reverted from the shock. However, groups that received MB in combination with BT, specifically Groups 3 and 4, exhibited statistically significant higher ratios of maximum MAP to baseline MAP., Conclusion: Using MB concomitant with BT allowed the reversal of hemorrhagic shock with higher median arterial pressure levels compared to BT alone or applying MB separately from BT. This suggests that simultaneous application of MB and BT could be a more effective strategy for reversing the effects of severe acute bleeding.

Purpose: Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase., Objective: To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to the Control group., Methods: This was a 1:1 randomized clinical trial of two groups (MB and Control). Forty-two patients were included in the present study; 23 patients were allocated to the Control group, and 19 were randomized to the MB group. Both groups had access to standard treatment, consisting of fluid replacement, vasopressors, and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 h. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 min (T2), 2 h (T3), 24 h (T4), 48 h after the infusion started (T5) and 24 h after weaning (T6)., Results: MB therapy was started together with the indication of vasopressin (VAS) as a second vasopressor. The MB group showed an immediate reduction in NOR dosage, an earlier reduction in VAS dosage, and higher IL-10 levels compared to the Control group., Conclusion: Early administration of MB in combination with standard treatment for septic shock might be reduce vasopressors dose. Continuous infusion of MB for 48 h was considered safe and there was no adverse events. These results highlight the potential of MB as a safe adjuvant therapeutic option in the treatment of septic shock., Clinical Trial Registration: https://clinicaltrials.gov/, identifier RBR-96584w4., 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., (Copyright © 2024 Luis-Silva, Menegueti, Peres, Sepeda, Jordani, Mestriner, Petroski-Moraes, Brito-de-Sousa, Costa-Rocha, Cruz, Donadel, de Souza, Reis, Bellissimo-Rodrigues, Basile-Filho, Becari, Evora, Martins-Filho and Auxiliadora-Martins.)

Microvasculature failure is expected in sepsis and at higher amine concentrations. Therefore, special attention focused individually on microcirculation is needed. Here, we present that methylene blue can prevent leukocytes from adhering to the endothelium in a rat model of lipopolysaccharide-induced endotoxemia. As hypothesis evidence, an intravital microscopy image is presented.

Objective: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database., Methods: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up., Results: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods., Conclusion: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Orosomucoid, or alpha-1 acid glycoprotein (AGP), is a major acute-phase protein expressed in response to systemic injury and inflammation. AGP has been described as an inhibitor of neutrophil migration on sepsis, particularly its immunomodulation effects. AGP's biological functions in coronavirus disease 2019 (COVID-19) are not understood. We sought to investigate the role of AGP in severe COVID-19 infection patients and neutrophils infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Epidemiological data, AGP levels, and other laboratory parameters were measured in blood samples from 56 subjects hospitalized in the ICU with SARS-CoV-2 infection. To evaluate the role of AGP in NETosis in neutrophils, blood samples from health patients were collected, and neutrophils were separated and infected with SARS-CoV-2. Those neutrophils were treated with AGP or vehicle, and NETosis was analyzed by flow cytometry. AGP was upregulated in severe COVID-19 patients (p<0.05). AGP level was positively correlated with IL-6 and C-reactive protein (respectively, p=0.005, p=0.002) and negatively correlated with lactate (p=0.004). AGP treatment downregulated early and late NETosis (respectively, 35.7% and 43.5%) in neutrophils infected with SARS-CoV-2 and up-regulated IL-6 supernatant culture expression (p<0.0001). Our data showed increased AGP in COVID-19 infection and contributed to NETosis regulation and increased IL-6 production, possibly related to the Cytokine storm in COVID-19., 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 Elsevier Ltd. All rights reserved.)

Background: Infectious endocarditis (IE) refers to infection of the endocardial surface of the heart and usually occurs in native or prosthetic valves., Objective: This study aimed to raise IE data reflecting the surgical therapy in a University Hospital in the interior of the State of Sao Paulo-Brazil., Method: Retrospective and observational approach of 328 patients with IE who underwent surgery between 1982 and 2020., Results: The main data (n=121/37%), congestive heart failure (n=114/35%), valve disease (n=92/28%), diabetes mellitus (n=85/26%), chronic kidney disease (n=59/18%), and rheumatic fever (49/15%). Renal failure is one of the main and most relevant pre-surgical risk factors for a poor prognosis., Conclusion: For a better clinical and surgical outcome, an early syndromic and etiological diagnosis of IE is necessary, especially in patients with multiple comorbidities.

Rationale: Methylene blue (MB) has been used to increase blood pressure in septic shock, acting on the activity of guanylate cyclase and nitric oxide synthase., Patience Concerns: The aim of this study is to demonstrate the benefit of MB in early phase of septic shock.Diagnoses: We report 6 cases of patients with septic shock with up to 72 hours of evolution., Interventions: We used MB after fluid replacement, use of norepinephrine and vasopressin. Patients received a loading dose of MB and maintenance for 48 hours., Outcomes: All patients presented a reduction in the dose of vasopressors and lactate levels soon after the administration of the loading dose of MB, an effect that was maintained with the maintenance dose for 48 hours. Interleukin 6 and interleukin 8 were elevated at the beginning of the septic condition, with a progressive and marked reduction after the beginning of MB infusion, demonstrating a role of MB in reducing the inflammatory activity., Lessons: This case series suggests that MB used early in the treatment of septic shock may be useful in reducing vasopressor dose and lactate levels. Further studies are still required to further validate these findings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The authors design an animal model of neonatal sepsis to analyze the treatment of neonatal septic shock with Methylene Blue (MB) in a swine model., Methods: The study design included twenty male newborn pigs divided into four groups: 1) The control group; 2) The sepsis group (induced with lipopolysaccharide); 3) The MB group, and 4) The MB-treated sepsis group. Septic shock was defined as Blood Pressure (BP) dropping 20% below the baseline value. Continuous Blood Pressure (BP), Nitric Oxide (NO) levels, cyclic Guanosine Monophosphate (cGMP), malondialdehyde acid, base excess, lactate, arterial blood gases, hematocrit, and echocardiography were analyzed., Results: The BP of the sepsis group treated with MB showed a slight improvement in the first hour after treatment; however, a significant difference was not observed compared to the untreated sepsis group. Besides hemodynamic stability, the current study did not show symptomatic pulmonary hypertension, suggesting that MB was safe in neonates and children. An improvement in Base Excel (BE) levels after MB administration in septic animals may indicate a possible improvement in microcirculation., Conclusion: The MB improved biomarkers related to septic shock prognosis, although an improvement in the blood levels could not be detected. MB might be a beneficial drug for hemodynamic instability in infants., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2022 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: There are many reasons to believe that the nitric oxide/guanosine 3'5' - cyclic monophosphate (or NO/cGMP) pathway on vasoplegic states is underestimated. To study indigo carmine (IC) as an alternative to methylene blue was the investigation rationale., Methods: The IC (3mg/kg intravenous infusion) study protocol included five experimental groups; 1) Control group - saline was injected at 0 and 10 minutes; 2) IC group - IC was injected at 0 and saline at 10 minutes; 3) compound 48/80 (C48/80) group - C48/80 was injected at 0 minute and saline at 10 minutes; 4) C48/80 + IC group - C48/80 was injected at 0 minute and IC at 10 minutes; and 5) IC + C48/80 group - IC was injected at 0 minute and C48/80 at 10 minutes. The studies were carried out by registering and measuring hemodynamic and blood gasometric parameters, including continuous cardiac output., Results: 1) The effects of the drugs (IC and C48/80) were more evident in the first 20 minutes of recording; 2) hypotensive responses were more pronounced in the C48/80 groups; 3) IC isolated or applied before C48/80 caused transient pulmonary hypertension; and 4) after the first 20 minutes, the pressure responses showed stability with apparent hypotension more pronounced in the C48/80 groups. Clinical observations showed significant hemodynamic instability and catastrophic anaphylactic reactions (agitation, pulmonary hypertension, severe bronchospasm, urticaria, high-intensity cyanosis, violent gastric hypersecretion, and ascites)., Conclusion: A global results analysis showed differences between groups only in the first 20 minutes of the experiments.

Introduction: Septic shock is a lethal disease responsible for a large proportion of deaths in the Intensive Care Unit (ICU), even with therapy centered on fluid resuscitation, use of vasopressors and empirical antibiotic therapy applied within the first hour of diagnosis. Considering the multifactorial pathophysiology of septic shock and the mechanism of action of vasopressors, some patients may not respond adequately, which can lead to the maintenance of vasodilatation, hypotension and increased morbidity, and mortality. This protocol aims to verify whether the use of methylene blue in septic patients with an early diagnosis can contribute to an earlier resolution of a shock compared to standard treatment., Methods and Analysis: This is a study protocol for a single-center randomized clinical trial design in an ICU of a tertiary university hospital. In this study, we intend to include 64 patients aged between 18 and 80 years with a diagnosis of septic shock, of any etiology, with up to 72 hours of evolution after volume restoration, using norepinephrine at a dose ≥0.2 μg/kg/min and vasopressin at a dose of 0.04 IU/min. After the initial approach, we will randomize patients into two groups, standard care, and standard care plus methylene blue. The sample size was calculated in order to show 30% differences in septic shock resolution between groups. The Research Ethics Committee approved the study, and all patients included will sign an informed consent form (Clinical registration: RBR-96584w4)., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The present review was carried out to describe publications on the use of methylene blue (MB) in pediatrics and neonatology, discussing dose, infusion rate, action characteristics, and possible benefits for a pediatric patient group. The research was performed on the data sources PubMed, BioMed Central, and Embase (updated on Aug 31, 2020) by two independent investigators. The selected articles included human studies that evaluated MB use in pediatric or neonatal patients with vasoplegia due to any cause, regardless of the applied methodology. The MB use and 0 to 18-years-old patients with vasodilatory shock were the adopted criteria. Exclusion criteria were the use of MB in patients without vasoplegia and patients ≥ 18-years-old. The primary endpoint was the increase in mean arterial pressure (MAP). Side effects and dose were also evaluated. Eleven studies were found, of which 10 were case reports, and 1 was a randomized clinical study. Only two of these studies were with neonatal patients (less than 28 days-old), reporting a small number of cases (1 and 6). All studies described the positive action of MB on MAP, allowing the decrease of vasoactive amines in several of them. No severe side effects or death related to the use of the medication were reported. The maximum dose used was 2 mg/kg, but there was no consensus on the infusion rate and drug administration timing. Finally, no theoretical or experimental basis sustains the decision to avoid MB in children claiming it can cause pulmonary hypertension. The same goes for the concern of a possible deleterious effect on inflammatory distress syndrome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Objective: A burn injury has two defined areas: central necrosis and an adjacent area of ischaemia, which may or may not progress to necrosis. The concentration of nitric oxide (NO) increases after burn injury and may originate from potent oxidising agents. Methylene blue (MB) may act as an antioxidant and is supposed to reduce burn progression. This investigation was carried out to evaluate the effects of intradermal MB on necrosis progression in burns., Methods: Full-thickness burn injuries were performed by applying a heated metal comb on the shaved back of male Wistar rats. The animals were divided into three groups: Control (C, n=7); MB (2mg/kg) one hour after burn injury (MB1h, n=11); and MB (2mg/kg) six hours after burn injury (MB6h, n=8). After seven days the lesions were photographed for visual assessment of burn necrosis; full-thickness cuts of lesions were dyed with Masson and Giemsa for microscopic histopathology; and tissue fragments of unburned interspaces were processed for chemiluminescence with nitrite/nitrate (NOX) and malondialdehyde (MDA) as oxidative stress markers., Results: No statistically significant differences between groups were observed during visual analysis and NOX dosage. However, in microscopic analysis, the MB1h and MB6h groups showed smaller areas of necrosis, less inflammatory infiltration, and a more significant extension of interspaces. Furthermore, the dosage of MDA revealed that the MB1h group showed lower values when compared with the control group (p=0.001)., Conclusions: The study provided good evidence that MB intradermal injection can reduce necrosis progression in ischaemic perilesional areas and suggests an alternative to treating burns.

Atrial septal aneurysm (ASA) is an uncommon but wellrecognized cardiac abnormality. This educational text reviews the case of a 54-year-old female presenting an ASA related to a small ostium secundum atrial septal defect. The considerable signs and symptoms, interestingly, have not been justified by the clinical and hemodynamic investigations. So, we opted for a better imaging investigation with cardiac catheterization and transesophageal echocardiography. The surgical process was earlier indicated and performed with aid of cardiopulmonary bypass.

Vasoplegic syndrome (VS) comprises a constellation of concurrent signs and symptoms: hypotension, high cardiac index, low systemic vascular resistance, low filling pressures, the tendency to occur diffuse bleeding, and sustained hypotension. All of these parameters may persist even despite the use of high doses of vasoconstrictor amines. VS arises from vasoplegic endothelial dysfunction with excessive release of nitric oxide by polymorphonuclear leukocytes mediated by the nitric oxide synthase's inducible form and is associated with systemic inflammatory reaction and high morbimortality. The achievements regarding the treatment of VS with methylene blue (MB) are a valuable Brazilian contribution to cardiac surgery. The present text review was designed to deliver the accumulated knowledge in the past ten years of employing MB to treat VS after cardiac surgery. Considering that we have already published two papers describing acquired experiences and concepts after 15 and 20 years, now, as we achieve the 30-year mark, we compose a trilogy.

Background: Usually viewed as a characteristic of old age, frailty may also occur in non-elderly people, primarily in those suffering from chronic disease. Frailty may increase operative risk., Objectives: To determine the prevalence of frailty patients undergoing coronary artery bypass (CABG) and/or heart valve replacement or reconstruction and/or heart valve surgery, as well as the influence of frailty on postoperative outcomes., Methods: Our study comprised 100 adults who underwent consecutive elective cardiac operations. Frailty was assessed using the Fried scale. Patients also performed a 6-minute walk test, and we measured maximal inspiratory and expiratory pressures. A p value <0.05 was considered significant., Results: Of a cohort of 100 patients, based on the Fried frailty criteria, 17 patients (17%) were considered frail, 70 (70%) pre-frail and only 13 (13%) were non-frail. Among patients with valvular heart disease, 11 (18.6%) were considered frail and 43 (73%) pre-frail. Fifty three percent of the patients considered frail were less than 60 years old (median=48 years old). The differences in frailty phenotype between patients with valvular heart disease and coronary artery disease were not statistically significant (p=0.305). A comparison between non-frail, pre-frail, and frail patients showed no significant difference in the distribution of comorbidities and cardiac functional status, regardless of their cardiac disease. However, hospital mortality was significantly higher in frail patients (29.4%, p=0.026) than in pre-frail patients (8.6%) and non-frail patients (0%)., Conclusions: Frailty is prevalent even among non-elderly patients undergoing CABG or valvular heart surgery and is associated with higher postoperative hospital mortality.

Background: Many studies have shown that the diterpenoid classes exert a significant effect on the cardiovascular system. Diterpenes, in particular, are among the main compound links to cardiovascular properties such as vasorelaxant, inotropic, diuretic and hypotensive activity. While the manool vasorelaxation mechanism is visible, its effect on blood pressure (BP) is still unknown., Objective: To evaluate the in vivo hypotensive effect of manool and check the ex vivo vasorelaxation effect in rat aortic rings., Methods: The animals were divided randomly into two groups: normotensive and hypertensive. The normotensive group was sham-operated, and the 2K1C model was adopted for the hypertensive group. Invasive BP monitoring was performed for manool tests at different doses (10, 20 and 40 mg/kg). Concentration-response curves for manool were obtained in the aorta rings, with endothelium, pre-contracted with phenylephrine (Phe) after incubation with Nω-nitro-L-arginine methyl ester(L-NAME) or oxadiazole [4,3-a]quinoxalin-1-one (ODQ). Nitric oxide (NOx) plasma levels were measured by chemiluminescence assay., Results: After manool administration, BP was reduced in normotensive and hypertensive groups, and this effect was inhibited by L-NAME in hypertensive animals only in 10 mg/kg dose. Ex vivo manool promoted vasorelaxation, which was inhibited by L-NAME and ODQ incubation or endothelium removal. NOx plasma levels increased in the hypertensive group after manool administration. Manool elicits endothelium-dependent vascular relaxation in rat aorta mediated by the NO/cGMP signaling pathway and BP reduction, also by NOx plasma increase. These combined effects could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene., Conclusion: These effects together could be involved in modulating peripheral resistance, contributing to the antihypertensive effect of diterpene.

Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

Traumatic left ventricular pseudoaneurysms are rare and surgical correction is the treatment of choice. In this article, it is reported a case of a myocardial stab injury with primary suture and development of a giant pseudoaneurysm, five years later, that underwent surgical repair.

Introduction: Adrenocortical and renal cell carcinomas rarely invade the right atrium (RA). These neoplasms need surgical treatment, are very aggressive and have poor prognostic and surgical outcomes., Case Series: We present a retrospective cohort of nine cases of RA invasion through the inferior vena cava (four adrenocortical carcinomas and five renal cell carcinomas). Over 13 years (2002-2014), nine patients were operated in collaboration with the team of urologists. Surgery was possible in all patients with different degrees of technical difficulty. All patients were operated considering the imaging examinations with the aid of CPB. In all reported cases (renal or suprarenal), the decision to use CPB with deep hypothermic circulatory arrest (DHCA) on surgical strategy was decided by the team of urological and cardiac surgeons., Conclusion: Data retrospectively collected from patients of public hospitals reaffirm: 1) Low incidence with small published series; 2) The selected cases did not represent the whole historical casuistry of the hospital, since they were selected after the adoption of electronic documentation; 3) Demographic data and references reported in the literature were presented as tables to avoid wordiness; 4) The series highlights the propensity to invade the venous system; 5) Possible surgical treatment with the aid of CPB in collaboration with the urology team; 6) CPB with DHCA is a safe and reliable option; 7) Poor prognosis with disappointing late results, even considering the adverse effects of CPB on cancer prognosis are expected but not confirmed.

Background: There is a definite association between antipsychotic drugs and arterial hypertension. However, endothelium functions are scarcely considered. This investigation was carried out to study the mechanisms involved in clozapine endothelium-dependent vascular reactivity., Methods: The experimental animals were male Wistar rats with a mean age of 70-90 days (250-300 g). The endothelium-dependent vascular reactivity was studied by measuring the isometric force and then constructing clozapine concentration-response curves. The force registrations were obtained in the aorta rings with and without the endothelium precontracted with phenylephrine (PE10 -6 M) treatment; this followed incubation for 30 min in "organ chambers" with different inhibitors: l- NAME (nitric oxide/cGMP); indomethacin (PGI2/cAMP); tetraethylammonium (TEA), and specific hyperpolarization blockers (paxillin, apamin, glibenclamide). The data were presented as the mean ± standard error of the mean (SEM) and were compared by one-way ANOVA or two-way ANOVA followed by the Bonferroni post-test., Results: The primary outcomes were: 1) Clozapine-induced endothelium-dependent relaxation was not inhibited by indomethacin, l-NAME, ODQ, and methylene blue (MB); 2) The combination of l-NAME + indomethacin partially prevented the relaxation; 3) Clozapine did not induce relaxation in vessels contracted with KCl; 4) TEA did not block the clozapine-induced relaxation in vessels precontracted with PE (10 -6 M); 5) The potassium channel blockers paxillin and apamin did not prevent relaxation but glibenclamide did., Conclusion: Concerning the mechanisms involved in clozapine endothelium-dependent vascular reactivity, the present study suggests that there is synergistic participation that probably occurs through a crosstalk mechanism of the cAMP, cGMPpathways and hyperpolarization., (Copyright © 2019. Published by Elsevier B.V.)

Background: Methylene blue (MB) has been advocated for the treatment of shock refractory to standard measures. MB is proposed to increase blood pressure in shock by interfering with guanylate cyclase and nitric oxide synthase (NOS) activity. Several studies have evaluated the vasoconstrictive and positive inotropic effects of MB in septic shock patients. However, there is a paucity of studies involving trauma patients., Case Report: A 4-year-old boy was hit by a truck while riding his bicycle and was treated with fluid resuscitation at the emergency department and then taken to the operating room for damage-control surgery. He had liver, diaphragm, rectal, and thoracic injuries. At the pediatric intensive care unit (PICU), he remained hypotensive despite volume, dopamine, epinephrine, and norepinephrine infusion. A dose of 0.5 mg/kg of i.v. MB was administered. During the next 2 h after MB administration, we were able to wean him off norepinephrine, and doses of epinephrine and dopamine were reduced. Ultimately, he was discharged from the PICU 13 days later in good condition. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trauma patients who have experienced bleeding and survived the initial insult are still at risk of dying from continuing systemic hypoperfusion and the resultant multiple organ dysfunctions. Use of a low dose of MB as an adjuvant to treat shock might improve survival of these patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

It is well known that during hepatic operative procedures, it is often critical that the irrigation is interrupted to avoid possible bleeding, blood transfusions, variable intensities, and their short and long-term consequences. It was believed in the past that the flow interruption should not exceed 20 minutes, which limited the use of this maneuver. However, it has been postulated that ischemia could be maintained for more than 60 minutes in healthy livers. The present paper review includes: 1) A brief introduction to justify the rationale of the review design; 2) Aspects of the pathophysiology of the three stages of the liver ischemia-reperfusion injury; 3) The innate and acquired immunity; 4) Oxidative stress; 5) Apoptosis and autophagy, Some essential biomarkers (Tumor Necrosis Factor-α, nitric oxide, metalloproteinases); and, finally; 6) Preventive ("cheating") strategies, non-pharmacological and pharmacological options to treat the liver IR injury.

A 57-year-old female patient received elective liver transplant due to nonalcoholic steatohepatitis complicated by hepatocellular carcinoma. Her preoperative Model for End-Stage Liver Disease score was 11. The total transplant ischemic time was 10 hours and 35 minutes, and the warm ischemic time was 35 minutes. Even with aggressive fluid overload and use of high concentrations of vasoactive amines, the patient developed possible primary graft dysfunction with poor response to fluids and vasopressor support, suggesting vasoplegic syndrome. On the basis of the hypothesis of vasoplegic syndrome, the patient received methylene blue intravenously (100 mg bolus for 12 h/1.5 mg/kg). The catastrophic situation was controlled. The patient's urine output markedly improved, she was subsequently weaned from vasoactive support, and mechanical ventilation was discontinued 2 days later. The patient was discharged on the 20th postoperative day.