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 effects of pharmacological blockade of the mitochondrial calcium uniporter on myocardial ischemia-reperfusion injury

“…ECG was monitored and recorded from the beginning of the stabilization period with a commercial acquisition system (AqDados 7.02; Lynx Tecnologia Ltda., Brazil) as reported earlier [9][10][11][12][13] . To assess heart rate, incidences of reperfusion-induced ventricular arrythmia (VA), atrioventricular block (AVB) and lethality (LET), raw data were analyzed with a commercial software package included in the acquisition system (AqDAnalysis 7, Lynx Tecnologia Ltda.).…”

Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection

“…Ischemic postconditioning also reduces the formation of free radicals, prolonged opening of MPTP, and ATP deficit production [41,42]. Our studies also indicate that the cardioprotection stimulated by ischemic postconditioning is less efficient than that induced by ischemic preconditioning [42]. In contrast to the beneficial effects observed in animal models, ischemic postconditioning in human using surrogate markers of myocardial salvage has yielded conflicting results [41].…”

“…Studies in animal models of myocardial infarction showed that ischemic postconditioning improved myocardial metabolic recovery and increased myocardial salvage [41,42]. Our studies in animal models of cardiac I/R injury indicate that ischemic postconditioning attenuates ionic imbalance in cardiac cells by reducing the cytosolic and mitochondrial Ca 2+ overload, thus reducing excitation-contraction decoupling and incidence of severe arrhythmias and lethality caused by I/R injury [42]. Ischemic postconditioning also reduces the formation of free radicals, prolonged opening of MPTP, and ATP deficit production [41,42].…”

“…Our studies in animal models of cardiac I/R injury indicate that ischemic postconditioning attenuates ionic imbalance in cardiac cells by reducing the cytosolic and mitochondrial Ca 2+ overload, thus reducing excitation-contraction decoupling and incidence of severe arrhythmias and lethality caused by I/R injury [42]. Ischemic postconditioning also reduces the formation of free radicals, prolonged opening of MPTP, and ATP deficit production [41,42]. Our studies also indicate that the cardioprotection stimulated by ischemic postconditioning is less efficient than that induced by ischemic preconditioning [42].…”

“…Some lines of investigation suggest that sympathetic hyperactivity associated to arterial hypertension constitutes a pathological condition that can potentially stimulate the cardioprotective response [42,56,57,58]. Studies performed in humans and animal models of primary arterial hypertension showed that this cardiovascular disease is associated with increased peripheral vascular resistance, progressive cardiac hypertrophy and heart failure, and sympathetic hyperactivity [56].…”