MiR-98-5p promotes ischemia/reperfusion-induced microvascular dysfunction by targeting NGF and is a potential biomarker for microvascular reperfusion.

OBJECTIVE: This study examined the correlation between serum miR-98-5p levels and indices of microvascular reperfusion in patients undergoing primary percutaneous coronary intervention (pPCI) after ST-segment elevation myocardial infarction (STEMI). Additionally, we evaluated the mechanisms by which miR-98-5p promoted ischemia/reperfusion (I/R)-induced injury in both cultured cell lines and an animal model. METHODS: Circulating miR-98-5p levels were measured and compared from 171 STEMI patients undergoing pPCI, who were divided into two groups: no-reflow and reflow. The levels of miR-98-5p, nerve growth factor (NGF), and transient receptor potential vanilloid 1 (TRPV1) were analyzed in cultured human coronary endothelial cells (HCECs) exposed to hypoxia/reoxygenation (H/R). The effects of antagomir-98-5p on myocardial I/R-induced microvascular dysfunction in vivo were evaluated. Target gene expression and activity were assessed. RESULTS: Higher miR-98-5p levels were associated with compromised indices of microvascular reperfusion. In vitro experiments on HCECs showed that exposure to H/R significantly increased miR-98-5p levels. We identified NGF as a novel target of miR-98-5p. Further, antagomir-98-5p relieved microvascular dysfunction and enhanced the expression of NGF and TRPV1 in the rat myocardial I/R model. CONCLUSIONS: MiR-98-5p promotes microvascular dysfunction by targeting the NGF-TRPV1 axis. Serum miR-98-5p serves as a potential biomarker for microvascular reperfusion.

The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery.

OBJECTIVE: To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG). METHODS: This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals. RESULTS: High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups. CONCLUSION: Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group. IRCT CODE: IRCT2016053019470N33.

The effect of high-dose vitamin c on biochemical markers of myocardial injury in coronary artery bypass surgery

Abstract Objective: To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG). Methods: This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals. Results: High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups. Conclusion: Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group. IRCT code: IRCT2016053019470N33

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion.

PURPOSE: To evaluate the cardioprotective response of the pharmacological modulation of ß-adrenergic receptors (ß-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. METHODS: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with ß-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with ß-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. RESULTS: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of ß-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of ß-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). CONCLUSION: The pharmacological modulation of ß-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

HDL-Targeted Therapies During Myocardial Infarction.

It is now apparent that a variety of deleterious mechanisms intrinsic to myocardial infarction (MI) exists and underlies its high residual lethality. Indeed, despite effective coronary patency therapies, ischemia and reperfusion (I/R) injury accounts for about 50% of the infarcted mass. In this context, recent studies in animal models have demonstrated that coronary reperfusion with high-density lipoproteins (HDL) may reduce MI size in up to 30%. A spectrum of mechanisms mediated by either HDL-related apolipoproteins or phospholipids attenuates myocardial cell death. Hence, promising therapeutic approaches such as infusion of reconstituted HDL particles, new HDL by genomic therapy, or the infusion of apoA-I mimetic peptides have been sought as a way of ensuring protection against I/R injury. In this review, we will explore the limitations and potential therapeutic effects of HDL therapies during the acute phase of MI.

Adverse interaction between HDL and the mass of myocardial infarction.

BACKGROUND AND AIMS: Coronary reperfusion with HDL from healthy volunteers attenuates ischemia and reperfusion injury in animal models. In myocardial infarction (MI) patients, such an interaction is unclear. Hence, our first objective was to verify if there is interaction between HDL-C and MI mass in patients and the role of coronary reperfusion in the interaction. Furthermore, we investigated whether the effect in MI size of reperfusion with HDL obtained from healthy participants or MI patients could differ. METHODS: HDL-C was measured the first day after MI and MI mass was quantified by cardiac magnetic resonance (n = 94) and peak CKMB (n = 393). In an ex vivo rat heart model, we compared MI area and dP/dt max after coronary reperfusion with HDL from MI patients or healthy volunteers. RESULTS: HDL-C above the median (35 mg/dL) was associated with higher peak CKMB [255 (145-415) vs. 136 (84-287) UI/L; p = 0.02], higher MI mass [17 (9-21) vs. 10 (6-14) g; p < 0.01] and lower left ventricular ejection fraction [47 (34-53) vs. 51 (43-59); p = 0.02] than their counterparts. In restricted cubic spline and multivariate linear regression, HDL-C was directly associated with peak CKMB (p < 0.01) and MI mass (p < 0.01) only in reperfused patients with time to reperfusion <4 h. Reperfusion with healthy HDL, but not from MI patients, reduced MI mass (p < 0.01) and improved dP/dt max (p = 0.02). CONCLUSIONS: In MI patients undergoing early coronary reperfusion, HDL-C levels at admission are directly associated with MI size. In contrast to healthy HDL, reperfusion with HDL from MI patients do not reduce MI area in an ex vivo animal model.

Pharmacological modulation of b-adrenoceptors as a new cardioprotective strategy for therapy of myocardial dysfunction induced by ischemia and reperfusion

Abstract Purpose: To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats. Methods: CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR. Results: The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO). Conclusion: The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion.

PURPOSE: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. METHODS: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). RESULTS: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. CONCLUSION: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Cardiac ischemia/reperfusion injury is inversely affected by thyroid hormones excess or deficiency in male Wistar rats.

AIM: Thyroid dysfunctions can increase the risk of myocardial ischemia and infarction. However, the repercussions on cardiac ischemia/reperfusion (IR) injury remain unclear so far. We report here the effects of hypothyroidism and thyrotoxicosis in the susceptibility to IR injury in isolated rat hearts compared to euthyroid condition and the potential role of antioxidant enzymes. METHODS: Hypothyroidism and thyrotoxicosis were induced by administration of methimazole (MMZ, 300 mg/L) and thyroxine (T4, 12 mg/L), respectively in drinking water for 35 days. Isolated hearts were submitted to IR and evaluated for mechanical dysfunctions and infarct size. Superoxide dismutase types 1 and 2 (SOD1 and SOD2), glutathione peroxidase types 1 and 3 (GPX 1 and GPX3) and catalase mRNA levels were assessed by quantitative RT-PCR to investigate the potential role of antioxidant enzymes. RESULTS: Thyrotoxicosis elicited cardiac hypertrophy and increased baseline mechanical performance, including increased left ventricle (LV) systolic pressure, LV developed pressure and derivatives of pressure (dP/dt), whereas in hypothyroid hearts exhibited decreased dP/dt. Post-ischemic recovery of LV end-diastolic pressure (LVEDP), LVDP and dP/dt was impaired in thyrotoxic rat hearts, whereas hypothyroid hearts exhibited improved LVEDP and decreased infarct size. Catalase expression was decreased by thyrotoxicosis. CONCLUSION: Thyrotoxicosis was correlated, at least in part, to cardiac remodeling and increased susceptibility to IR injury possibly due to down-regulation of antioxidant enzymes, whereas hypothyroid hearts were less vulnerable to IR injury.

Effect of total peony glucoside pretreatment on NF-κB and ICAM-1 expression in myocardial tissue of rat with myocardial ischemia-reperfusion injury.

Early recovery of myocardial perfusion is beneficial for myocardial ischemia. However, ischemia-reperfusion (I/R) may exacerbate myocardial injury. Research shows that total peony glucoside (TPG) can inhibit ischemic myocardial cell apoptosis. However, whether it can ameliorate I/R injury remains poorly understood. This study explored the effect of TPG pretreatment on I/R, through nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) expressions in I/R-affected myocardium. Healthy 7-week-old male Sprague Dawley rats were randomly categorized into sham operation (A), modeling (B), and 100, 200, and 400 mg/kg TPG pretreatment groups (C, D, and E, respectively), with 20 rats in each group. I/R rat models were designed by ligating left anterior descending coronary artery for 30 min to induce ischemia and for 120 min to induce reperfusion. Serum interleukin 6 (IL-6) and interleukin 8 (IL-8) levels were measured using enzyme linked immunosorbent assay. NF-κB and ICAM-1 mRNA and protein expressions were detected through RT-PCR and western blot analysis, respectively. Compared to group A, serum IL-6 and IL-8 levels of group B elevated significantly (P < 0.05), whereas NF-κB and ICAM-1 mRNA and protein expressions increased in the myocardium (P < 0.05). Serum IL-6 and IL-8 levels, and NF-κB and ICAM-1 mRNA and protein expressions, in myocardium of TPG groups reduced in a dose-dependent manner. Therefore, TPG pretreatment could alleviate myocardium reperfusion injury in I/R rat models by reducing NF-κB and ICAM-1 mRNA and protein expressions and cytokine secretions. This mechanism could be associated with the inhibition of NF-κB activation and downregulation of ICAM-1 expression.

Amelioration of persistent left ventricular function impairment through increased plasma ascorbate levels following myocardial infarction.

PURPOSE: Percutaneous coronary angioplasty (PCA) has been demonstrated to reduce mortality and morbidity and thereby improve the prognosis of patients undergoing acute myocardial infarctions (AMIs). However, this procedure paradoxically increases the initial damage as the result of a condition known as 'myocardial reperfusion injury'. Oxidative stress may contribute to the mechanism of this injury. The goal of the present study was to ascertain whether high plasma ascorbate levels could ameliorate the reperfusion injuries that occur after the successful restoration of blood flow. METHODS: Patients from three clinical centers of the public health system were included in the study. The groups were formed by either-sex patients with a diagnosis of ST-segment elevation myocardial infarction with an indication for primary PCA. Only the patients who presented with their first myocardial infarction were enrolled. Ascorbate was administered through an infusion given prior to the restoration of the coronary flow, which was then followed by oral treatment with vitamin C (500 mg/12 hours) plus vitamin E (400 IU/day) for 84 days. The left ventricular ejection fraction (LVEF) was determined by using cardiac magnetic resonance on days 6 and 84 following the onset of the reperfusion. In addition, the microvascular function was assessed by an angiographic evaluation using the Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade (TMPG). The results were grouped according to the plasma ascorbate concentration achieved immediately following the onset of reperfusion into either the HA group (high ascorbate, >1 mmol/l) or the LA group (low ascorbate, <1 mmol/l). The biochemical parameters were analyzed throughout the protocol. RESULTS: The LVEF of the HA group was significantly higher than that of the LA group, values on day 84 in the HA group were 33% higher than those of the LA group. The amelioration of the LVEF was accompanied by an improvement in the microvascular dysfunction, after PCA, 95% of the patients in the HA group achieved a TMPG of 2-3, in the LA group only 79% of patients showed a TMPG of 2-3. CONCLUSIONS: These data are consistent with the protective effect of high plasma levels of ascorbate against the oxidative challenge caused by reperfusion injury in patients subjected to PCA following an AMI. Further studies are needed to elucidate the mechanism accounting for this beneficial antioxidant effect.

Variation of plasma levels of endothelin, calcitonin gene-related peptide, nitric oxide, and malondialdehyde in acute myocardial ischemia reperfusion injury in a rabbit model.

We examined the variation in plasma levels of endothelin (ET), calcitonin gene-related peptide (CGRP), nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) activity, in acute myocardial ischemia reperfusion injury in a rabbit model. Seventy rabbits were randomly assigned into 3 groups. Open-chest surgery (OCS) was performed for all rabbits. Group A (N = 20) received sham-surgery, group B (N = 25) was the reperfusion group, and group C (N = 25) was the infarction group. At 12 h after chest clo-sure, plasma ET levels in groups B and C were clearly increased, while CGRP levels were clearly decreased, particularly in group B. At 24 h after chest closure, ET levels were higher than before OCS, while there was no significant difference between groups B and C. ET in group B was decreased, while that in group C was increased at 12 h. No significant difference in CGRP was observed between 12 and 24 h after chest closure. NO levels in groups B and C at 12 h after chest closure were significantly decreased compared to those before OCS. NO levels in group B at 24, 48, and 72 h were significantly lower than those at 12 h, while those of group C were not significantly changed after 12 h. Dynamic monitoring and comparison of plasma levels of ET, CGRP, NO, and MDA as well as SOD activity revealed that appropriate intervention of these factors may reduce reperfusion injury.

Myocardial protective effects of Munziq in myocardial ischemia-reperfusion injury rats with abnormal savda syndrome.

This study evaluated the influence and mechanism of different Munziq doses on myocardial ischemia reperfusion injury (MIRI) rats with abnormal savda. Wistar rats (N = 96) were divided into the following 8 groups (12 rats each): ischemia-reperfusion (I/R) model group, high-dose, medium-dose, and low-dose Munziq groups, normal I/R group, sham model group, normal sham group, and Atorvastatin group. Changes in heart physiology and myocardial morphology after injury with MIRI were monitored in each group. Heat shock protein 70 (HSP70) and calcitonin gene-related peptide (CGRP) protein expression and serum concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, and IL-8 were detected by using western blot and ELISA methods, respectively. The large-dose Munziq group showed the most significant changes. The VPC incurring time was not delayed in the small-dose group, but the accumulative time was significantly reduced (P < 0.01). The ventricular tachycardia incurring time did not differ significantly between groups. Compared with the normal sham surgical group, the I/R groups showed significant increases in HSP70 and CGRP expression (P < 0.01) and MDA, IL-6, and IL-8 concentrations (P < 0.05) and a significant decrease in the SOD concentration (P < 0.05). Compared with the I/R groups, Munziq intervention significantly enhanced HSP70 and CGRP expression (P < 0.01), significantly decreased MDA, IL-6, and IL-8 concentrations (P < 0.05), and significantly increased the SOD concentration (P < 0.05). In conclusion, Munziq intervention improves cardiac physiological function, increases the expression of HSP70 and CGRP, and decreases the inflammatory reaction in MIRI model rats.

Effects of different doses of Savda Munziq on myocardial ischemia-reperfusion injury in rats with abnormal Savda syndrome.

To investigate the effects of different doses of abnormal Savda Munziq on myocardial ischemia-reperfusion injury (MI/RI) in rats with the abnormal Savda syndrome, 50 abnormal Savda animal models were randomly divided into a control group, a model group, a high-dose group, a middle-dose group, and a low-dose group, with each group containing 10 rats. The enzyme-linked immunosorbent assay was used to detect the serum myocardial enzyme and troponin levels, and hematoxylin and eosin (HE) staining was used to observe changes of the myocardial tissues in the different groups. Results showed that in the Munziq intervention groups, the serum creatine kinase and troponin levels were significantly lower than those in the model group, and the middle-dose group showed the lowest levels. The HE staining of myocardial tissue showed that the myocardial edema and muscle fiber proliferation levels were significantly higher in the Munziq intervention groups than in the model group, and the middle-dose group showed the least cardiac tissue damage. Therefore, intervention with an intermediate Munziq dose could significantly reduce MI/RI in rats with abnormal Savda syndrome.

The effectiveness of antioxidant vitamins C and E in reducing myocardial infarct size in patients subjected to percutaneous coronary angioplasty (PREVEC Trial): study protocol for a pilot randomized double-blind controlled trial.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of mortality worldwide. Oxidative stress has been involved in the ischemia-reperfusion injury in AMI. It has been suggested that reperfusion accounts for up to 50% of the final size of a myocardial infarct, a part of the damage likely to be prevented.Therefore, we propose that antioxidant reinforcement through vitamins C and E supplementation should protect against the ischemia-reperfusion damage, thus decreasing infarct size.The PREVEC Trial (Prevention of reperfusion damage associated with percutaneous coronary angioplasty following acute myocardial infarction) seeks to evaluate whether antioxidant vitamins C and E reduce infarct size in patients subjected to percutaneous coronary angioplasty after AMI. METHODS/DESIGN: This is a randomized, 1:1, double-blind, placebo-controlled clinical trial.The study takes place at two centers in Chile: University of Chile Clinical Hospital and San Borja Arriarán Clinical Hospital.The subjects will be 134 adults with acute myocardial infarction with indication for percutaneous coronary angioplasty.This intervention is being performed as a pilot study, involving high-dose vitamin C infusion plus oral administration of vitamin E (Vitamin-treatment group) or placebo (Control group) during the angioplasty procedure. Afterward, the Vitamin-treatment group receives oral doses of vitamins C and E, and the Control group receives placebo for 84 days after coronary angioplasty.Primary outcome is infarct size, assessed by cardiac magnetic resonance (CMR), measured 6 and 84 days after coronary angioplasty.Secondary outcomes are ejection fraction, measured 6 and 84 days after coronary angioplasty with CMR, and biomarkers for oxidative stress, antioxidant status, heart damage, and inflammation, which will be measured at baseline, at the onset of reperfusion, 6 to 8 hours after revascularization, and at hospital discharge. DISCUSSION: The ischemia-reperfusion event occurring during angioplasty is known to increase myocardial infarct size. The cardioprotective benefits of high doses of vitamin C combined with vitamin E have not been fully explored. The PREVEC Trial seeks to determine the suitability of the therapeutic use of vitamins C and E against the reperfusion damage produced during angioplasty.Patient recruitment opened in February 2013. The trial is scheduled to end in March 2016. TRIAL REGISTRATION: ISRCTN56034553.

Oxidative stress-related biomarkers in essential hypertension and ischemia-reperfusion myocardial damage.

Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers.

Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts.

OBJECTIVE: A simple method to reduce the ischemia/reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. METHOD: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. RESULTS: Rat hearts with hyperosmotic perfusion showed higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, P<0.005), a lower reperfusion arrthythmia score (3.2 vs. 5.3, P<0.001), better ventricular function, and less creatine phosphokinase leakage (340.1 vs. 861.9, P<0.001) than normal osmotic controls. Myocardial catalase content and activity were increased significantly (1435 vs. 917 U/g wet weight, P<0.001) in hearts perfused with hyperosmotic solution in comparison to the normal osmotic controls. CONCLUSION: Pretreatment with hyperosmotic perfusion in normal rat hearts, which is attributed partly to the increased antioxidative activity, could provide beneficial effects from ischemia and reperfusion-induced injury by increasing coronary flow, and decreasing reperfusion arrhythmia.

Beneficial effects of hyperosmotic perfusion in the myocardium after ischemia/reperfusion injury in isolated rat hearts / Efeitos benéficos da perfusão hiperosmótica no miocárdio após lesão isquemia/reperfusão em corações isolados de ratos

OBJECTIVE: A simple method to reduce the ischemia/reperfusion injury that can accompany cardiac surgery would have great clinical value. This study was to investigate the effect of hyperosmotic perfusion on ischemia/reperfusion injury in isolated perfused rat hearts. METHOD: Forty male Sprague-Dawley rats were randomly divided either to have their isolated hearts perfused with normal osmotic buffer or buffer made hyperosmotic by addition of glucose. Hearts were then subjected to 30 min ischemia followed by 30 min reperfusion. Coronary flow, time to ischemic arrest, reperfusion arrhythmia, and ventricular function were recorded. Creatine phosphokinase leakage into the coronary artery, and myocardial content and activity of superoxide dismutase and catalase were also examined. RESULTS: Rat hearts with hyperosmotic perfusion showed higher coronary flow, a prolonged time to ischemic arrest (10.60 vs. 5.63 min, P<0.005), a lower reperfusion arrthythmia score (3.2 vs. 5.3, P<0.001), better ventricular function, and less creatine phosphokinase leakage (340.1 vs. 861.9, P<0.001) than normal osmotic controls. Myocardial catalase content and activity were increased significantly (1435 vs. 917 U/g wet weight, P<0.001) in hearts perfused with hyperosmotic solution in comparison to the normal osmotic controls. CONCLUSION: Pretreatment with hyperosmotic perfusion in normal rat hearts, which is attributed partly to the increased antioxidative activity, could provide beneficial effects from ischemia and reperfusion-induced injury by increasing coronary flow, and decreasing reperfusion arrhythmia.

OBJETIVO: Um método simples para reduzir a lesão de isquemia/reperfusão que pode acompanhar a cirurgia cardíaca teria grande valor clínico. O objetivo deste estudo foi investigar o efeito da perfusão hiperosmótica na isquemia/reperfusão em corações isolados de ratos perfundidos. MÉTODOS: Quarenta ratos machos Sprague-Dawley foram divididos aleatoriamente e tiveram os seus corações isolados perfundidos com tampão osmótico normal ou tampão hiperosmótico com a adição de glucose. Os corações foram então submetidos a 30 minutos de isquemia, seguida de 30 min de reperfusão. O fluxo coronariano, tempo de parada isquêmica, arritmia de reperfusão e da função ventricular foram registrados. Vazamento creatinofosfoquinase na artéria coronária, o miocárdio e atividade de superóxido dismutase e catalase foram também examinados. RESULTADOS: Crações de ratos com perfusão hiperosmótica apresentaram maior fluxo coronariano, tempo prolongado de parada isquêmica (10,60 vs. 5,63 min, P<0,005), menor pontuação de reperfusão arritmica (3,2 vs. 5,3, P<0,001), melhor função ventricular e menos vazamento de creatina fosfoquinase (340,1 vs. 861,9, P<0,001) do que controles normais osmóticos. Teor de catalase e atividade do miocárdio também tiveram aumento significativo (1435 vs. 917 peso U/g de peso fresco, P<0,001) em corações perfundidos com solução hiperosmótica em comparação com os controles normais osmóticos. CONCLUSÃO: O pré-tratamento com perfusão hiperosmótica em corações de ratos normais, o que é atribuído, em parte, ao aumento da atividade antioxidante, pode oferecer efeitos benéficos de isquemia e reperfusão induzida por lesão, aumentando o fluxo coronário e diminuindo a arritmia de reperfusão.

Sexual hormones: effects on cardiac and mitochondrial activity after ischemia-reperfusion in adult rats. Gender difference.

In this work we studied the influence of sex hormones on heart and mitochondrial functions, from adult castrated female and male, and intact rats. Castration was performed at their third week of life and on the fourth month animals were subjected to heart ischemia and reperfusion. Electrocardiogram and blood pressure recordings were made, cytokines levels were measured, histopathological studies were performed and thiobarbituric acid reactive species were determined. At the mitochondrial level respiratory control, transmembranal potential and calcium management were determined; Western blot of some mitochondrial components was also performed. Alterations in cardiac function were worst in intact males and castrated females as compared with those found in intact females and castrated males, cytokine levels were modulated also by hormonal status. Regarding mitochondria, in those obtained from hearts from castrated females without ischemia-reperfusion, all evaluated parameters were similar to those observed in mitochondria after ischemia-reperfusion. The results show hormonal influences on the heart at functional and mitochondrial levels.