exenatide and Myocardial-Ischemia

Experimental studies of acute myocardial infarction have revealed that up to half of the final infarct size may be due to reperfusion injury rather than the initial ischemic incident. Research over the past three decades has deepened our understanding of the molecular mechanisms underlying ischemic reperfusion injury and several therapeutic strategies to decrease the incidence and severity of reperfusion injury have been explored.. To discuss the promising therapies and future perspectives on methods to attenuate myocardial reperfusion injury.. Existing therapies that address reperfusion can be divided into two major groups comprising nonpharmacological and pharmacological interventions. Myriad pharmacological and nonpharmacological approaches to reduce lethal reperfusion injury have been employed. Although many initial clinical studies were negative, more recent proof-of-concept clinical trials are promising. To date, the most encouraging results are with ischemic postconditioning, remote ischemic preconditioning, ANP, adenosine, cyclosporine and exenatide.. Studies demonstrate that nonpharmacological and pharmacological conditioning can be used together as part of a multifaceted approach to improve clinical outcomes in patients with ischemic heart disease.

Topics: Adenosine; Animals; Atrial Natriuretic Factor; Clinical Trials as Topic; Combined Modality Therapy; Cyclosporine; Disease Models, Animal; Exenatide; Humans; Ischemic Postconditioning; Ischemic Preconditioning; Myocardial Ischemia; Myocardial Reperfusion Injury; Peptides; Venoms

Glucagon-like peptide-1 and its receptor agonist-exendin-4 (Ex-4) have been shown to provide beneficial effects for cardiovascular diseases. This study investigated the effects of Ex-4 on ischemia-induced ventricular arrhythmias in rats.. Anesthetized male rats were once treated with Ex-4 (5 μg/kg, i.v.) 1 h before ischemia in the absence and/or presence of 5-hydroxydecanoic acid (5-HD, 10 mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium [KATP] channels) which were once injected 10 min before ischemia. And then subjected to ischemia for 30 min. Ventricular arrhythmias were assessed.. During the 30-min ischemia, Ex-4 significantly reduced the incidence of ventricular fibrillation (VF) (p < 0.05). The duration of ventricular tachycardia (VT) + VF, the number of VT + VF episodes and the severity of arrhythmias were all significantly reduced by Ex-4 compared to those in myocardial ischemia group (p < 0.05 for all). Administration of 5-HD abolished the protective effects of Ex-4 on VF incidence, the duration of VT + VF, the number of VT + VF episodes and the severity of arrhythmias (p < 0.05 for all).. This study suggested that Ex-4 could attenuate ischemia-induced ventricular arrhythmias in rats in which mitochondrial KATP channels may be involved.

Topics: Animals; Anti-Arrhythmia Agents; Blood Pressure; Decanoic Acids; Disease Models, Animal; Exenatide; Heart Rate; Hydroxy Acids; Hypoglycemic Agents; Male; Myocardial Ischemia; Peptides; Potassium Channel Blockers; Potassium Channels; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Venoms; Ventricular Fibrillation

Topics: Cardiotonic Agents; Diabetes Complications; Exenatide; Glucagon-Like Peptide 1; Heart; Humans; Hypoglycemic Agents; Incretins; Insulin; Insulin Secretion; Liraglutide; Myocardial Ischemia; Peptides; Venoms