enalaprilat-anhydrous and Tachycardia--Ventricular

Based on clinical and experimental studies, angiotensin II receptor blockers and angiotensin converting enzyme inhibitors have been proposed to exert acute anti-arrhythmic effects in heart failure patients. Therefore, the goal of this study was to assess acute anti-arrhythmic effects of losartan and enalaprilat in hypertrophied rat hearts during low-flow ischaemia and reperfusion. In dose-finding experiments in non-hypertrophied isolated perfused hearts, we performed dose-response curves of losartan and enalaprilat studying monophasic action potential duration at 90% repolarisation (MAPD(90%)) and ventricular fibrillation (VF) threshold. Subsequently, we determined the effects of losartan and enalaprilat (in therapeutically relevant concentrations) on ventricular tachyarrhythmias induced by low-flow ischaemia/reperfusion in hearts demonstrating left ventricular (LV) hypertrophy 70 days after aortic banding. We found that neither drug significantly affected MAPD(90%) (1 nM-1 mM) or VF threshold (1 microM losartan and 10 microM enalaprilat) in non-hypertrophied hearts. Similarly in hypertrophied hearts, neither drug significantly affected the incidence or the duration of ventricular tachyarrhythmias (ventricular tachycardia and VF) during low-flow ischaemia. However, 1 microM losartan significantly reduced the duration of ventricular tachyarrhythmias during reperfusion. In conclusion, neither losartan nor enalaprilat is acutely anti-arrhythmic in hypertrophied rat hearts during low-flow ischaemia. During reperfusion, however, losartan but not enalaprilat exerts acute anti-arrhythmic effects.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Dose-Response Relationship, Drug; Enalaprilat; Heart; Hypertrophy, Left Ventricular; In Vitro Techniques; Losartan; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tachycardia, Ventricular; Ventricular Fibrillation

This experimental study was undertaken to determine whether using angiotensin-converting enzyme inhibitors during surgical revascularization of acutely ischemic myocardium would improve wall motion and limit infarct size.. Twenty pigs underwent 90 minutes of occlusion of the second and third diagonal arteries followed by 45 minutes of cardioplegic arrest and 180 minutes of reperfusion. In 10 animals, the angiotensin-converting enzyme inhibitor enalaprilat (0.05 mg/kg) was infused intravenously during coronary occlusion; 10 other animals received no angiotensin-converting enzyme inhibitors. Ischemic damage was assessed by the number of cardioversions required for ventricular tachycardia or fibrillation; wall motion scores using echocardiography (4=normal to -1=dyskinesia); and infarct size using histochemical staining. Epicardial coronary artery vasomotor function was assessed using standard organ chamber methodology.. Enalaprilat-treated hearts had the least amount of ventricular irritability (0.84+/-0.24 versus 2.77+/-0.22 cardioversions; p < 0.01), the best recovery of wall motion score (3.20+/-0.15 versus 1.52+/-0.07; p < 0.0001), and the lowest infarct size (22.6%+/-1.4% versus 37.7%+/-3.0%; p < 0.001). Endothelium-independent relaxation was preserved in all hearts; however, endothelium-dependent relaxation was impaired in both groups.. Angiotensin-converting enzyme inhibitors reduce myocardial damage during surgical revascularization of acutely ischemic myocardium.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Coronary Vessels; Echocardiography; Electric Countershock; Enalaprilat; Heart Arrest, Induced; Heart Rate; Infusions, Intravenous; Myocardial Revascularization; Swine; Tachycardia, Ventricular; Vasomotor System; Ventricular Fibrillation