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

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

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.

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.

Trimetazidina na injúria de isquemia e reperfusão em cirurgia de revascularização do miocárdio / Trimetazidine on ischemic injury and reperfusion in coronary artery bypass grafting

FUNDAMENTO: A injúria de isquemia e reperfusão constitui um mecanismo fisiopatológico frequente e de difícil controle durante a Cirurgia de Revascularização do Miocárdio (CRVM) com circulação extracorpórea, sendo o momento crítico o término da cirurgia, quando ocorre o desclampeamento da aorta e a liberação dos radicais hiperóxidos causadores da injúria. OBJETIVO: Avaliar, em estudo prospectivo, duplo-cego randomizado, controlado com placebo, os efeitos da Trimetazidina (Tmz) sobre a injúria de isquemia e reperfusão miocárdica, identificando a variação dos marcadores plasmáticos de agressão miocárdica (troponina T e Cpk-Mb), e as alterações ecocardiográficas da função ventricular. MÉTODOS: Foram estudados 60 pacientes, divididos em dois grupos (Placebo e Tmz) com, no máximo, disfunção ventricular leve, estratificados por ecocardiografia e recebendo medicação/placebo na dose - no pré-operatório sem medicação, 12 a 15 dias de medicação/placebo colhida cinco minutos após o desclampeamento aórtico, e nas 12, 24 e 48 horas seguintes. RESULTADOS: Tanto a troponina T como a CpK-Mb atingiram valores altamente significativos (p = 0,0001) no grupo tratado em relação ao grupo controle nos quatro momentos analisados − 5 min, 12 h, 24 h e 48 h. As variáveis ecocardiográficas não evidenciaram mudanças evolutivas em cada grupo isoladamente e quando comparados em conjunto. CONCLUSÃO: A trimetazidina mostrou-se eficaz na redução da injúria de isquemia e reperfusão, não interferiu na função ventricular esquerda, e não foram observados efeitos colaterais.

BACKGROUND: The ischemia and reperfusion ischemia is a common physiopathological mechanisms, which has difficult control during Coronary Artery Bypass Grafting (CABG) with cardiopulmonary bypass, the critical moment of which happening by the end of surgery, when there is declamping of aorta and release of hyperoxic radicals causing the injury. OBJECTIVE: Evaluate, in a randomized double-blind prospective study, controlled with placebo, the effects of Trimetazidine (Tmz) on ischemic injury and myocardial reperfusion, identifying the change in plasma markers of a myocardial aggression (troponin T and CPK-MB), and echocardiographic changes of ventricular function. METHODS: We studied 60 patients divided in two groups (placebo and Tmz) with mild ventricular dysfunction at the most, stratified by echocardiography and receiving medication/placebo at a dose of 20 mg/3x/day, starting from 12 to 15 days after pre-operative period up to 5 to 8 days after post-operative period. Troponin T and Cpk-Mb were measured preoperatively without medication, 12 to 15 days of medication/placebo taken five minutes after aortic declamping, and at subsequent 12, 24 and 48 hours. RESULTS: Both Troponin T and Cpk-Mb reached highly significant values (p = 0.0001) in the treated group compared to the control group at the four moments analyzed - 5 min, 12h, 24h and 48h. The echocardiographic variables did not show evolutive changes in each group severally considered and when compared among themselves. CONCLUSION: Trimetazidine was effective in reducing ischemic injury and reperfusion, had no effect on left ventricular function, and no side effects were observed.

Changes in vitamin C and vitamin E during oxidative stress in myocardial reperfusion.

Injury to the myocardial tissue due to ischemia and reperfusion occurs because of imbalance between the formation of oxidants and available antioxidants in the heart. Levels of vitamin C (ascorbic acid) and vitamin E (alpha--tocopherol) were evaluated in 52 patients of acute myocardial infarction (AMI) treated by streptokinase. They were further divided into reperfused group (39 patients) and non-reperfused group (13 patients). Twenty normal healthy subjects served as controls. Vitamin C and vitamin E were estimated in study group before and after thrombolytic therapy and in controls. Vitamin C levels were low in AMI cases as compared to controls (8.74 +/- 1.87 and 10.63 +/- 3.26 mg/L, respectively, P < 0.001). Trend of fall in vitamin C levels in the two study groups was not statistically significant. Vitamin E levels declined from 12.19 +/- 6.71 to 9.96 +/- 6.50 mg/L by 4 hours which was significant (P < 0.01) in the reperfused group, but the change in non-reperfused group (9.28 +/- 6.37 to 9.35 +/- 6.07 mg/dL by 4 hours) was non-significant. This is because of increased consumption of this antioxidant in suppressing the oxidative stress which occurs with reperfusion. Vitamin E can be proposed as a valid marker for reperfusion.