Clin. Cardiol. 13, VII-49-52 (1990)
The Role of ACE Inhibitors in the Treatment of Arrhythmias W. J . MCKENNA.M.D., G. A. HAYWOOD,M.R.C.P.
Department of CardiologicalSciences,St. George’s Hospital Medical School, London, England
Summary: Several experimental models have been studied to determine the role of angiotensin-convertingenzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. Studies of left main coronary artery occlusion in isolated perfused rat hearts have shown that the ACE inhibitor captopril reduced reperfusion ventricular fibrillation from 100% to 0% and was associated with a reduction in burine overflow and in norepinephrine release. These effects were abolished in the presence of indomethacin. In an anesthetized rat model of acute myocardial infarction (MI), ACE inhibition reduced mean duration of ventricular fibrillation from 1,133 to 135. ACE inhibition at programmed electrical stimulation of the heart in a closed-chest pig model of acute MI reduced the inducibility of sustained, reproducible ventricular tachycardia from a mean of 42 to 8%. In this model, ventricular tachycardia could not be provoked in animals treated with captopril from the time of acute ischemia. Siudies on the rate of ventricular ectopy in patients with poor left ventricular function have demonstrated a significant reduction with ACE inhibition. However, while a protective effect has been shown, the mechanism of action is still speculative. Key words: arrhythmias, experimental, angiotensinconverting enzyme inhibitors, ventricular fibrillation
Introduction Ventricular arrhythmias are a major cause of sudden death in patients with chronic heart disease. These arrhyth-
Address for reprints:
William J . McKenna, M.D. Department of Catdiological Sciences St. George’s Hospital Medical School Cranmer Terrace London SW17 ORE, England
mias may also occur early during the Onset of an acute myocardial infarction (MI) or during reperfusion of an ischemic area after spontaneous or drug-induced relaxation of arterial spasm or thrombolysis. EKG monitoring data from patients who died suddenly while attached to a Holter monitor indicate that, in those with ischemic heart disease, about 75 % of deaths were caused by tachyarrhythmias and 25% by bradyarrhythmias.’ In the past several years, experimental animal models have been studied to determine the potential role of angiottnsin-convertingenzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. We discuss some of these experirnental models as well as the proposed mechanisms of protective effect.
Rat Models Studies have been performed in various rat models (Table I). One of the earliest of these studied the effects of the ACE inhibitor captopril on the incidence and duration of reperfusion arrhythmias following experimentally induced myocardial ischemia in the isolated rat heart.* Acute regional ischemia was induced by ligation of the left coronary artery: kpefision was produced by releasing the ligation, thus prbvoking Ventricular arrhythmias. One group of rat hearts seyed as conttol; in the other, captopril 80 pg/ml was added to the perfusion injection at the start of the control penod. Treatment with captopril ?educed both the incidence and duktion of ventricular fibrillation. At the onset of reperfusion, all of the control hearts showed ventricular fibrillation, whereas ventricular filbrillation occurred in only 40% of captopri1;treated hearts (p
The Role of ACE Inhibitors in the Treatment of Arrhythmias W. J . MCKENNA.M.D., G. A. HAYWOOD,M.R.C.P.
Department of CardiologicalSciences,St. George’s Hospital Medical School, London, England
Summary: Several experimental models have been studied to determine the role of angiotensin-convertingenzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. Studies of left main coronary artery occlusion in isolated perfused rat hearts have shown that the ACE inhibitor captopril reduced reperfusion ventricular fibrillation from 100% to 0% and was associated with a reduction in burine overflow and in norepinephrine release. These effects were abolished in the presence of indomethacin. In an anesthetized rat model of acute myocardial infarction (MI), ACE inhibition reduced mean duration of ventricular fibrillation from 1,133 to 135. ACE inhibition at programmed electrical stimulation of the heart in a closed-chest pig model of acute MI reduced the inducibility of sustained, reproducible ventricular tachycardia from a mean of 42 to 8%. In this model, ventricular tachycardia could not be provoked in animals treated with captopril from the time of acute ischemia. Siudies on the rate of ventricular ectopy in patients with poor left ventricular function have demonstrated a significant reduction with ACE inhibition. However, while a protective effect has been shown, the mechanism of action is still speculative. Key words: arrhythmias, experimental, angiotensinconverting enzyme inhibitors, ventricular fibrillation
Introduction Ventricular arrhythmias are a major cause of sudden death in patients with chronic heart disease. These arrhyth-
Address for reprints:
William J . McKenna, M.D. Department of Catdiological Sciences St. George’s Hospital Medical School Cranmer Terrace London SW17 ORE, England
mias may also occur early during the Onset of an acute myocardial infarction (MI) or during reperfusion of an ischemic area after spontaneous or drug-induced relaxation of arterial spasm or thrombolysis. EKG monitoring data from patients who died suddenly while attached to a Holter monitor indicate that, in those with ischemic heart disease, about 75 % of deaths were caused by tachyarrhythmias and 25% by bradyarrhythmias.’ In the past several years, experimental animal models have been studied to determine the potential role of angiottnsin-convertingenzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. We discuss some of these experirnental models as well as the proposed mechanisms of protective effect.
Rat Models Studies have been performed in various rat models (Table I). One of the earliest of these studied the effects of the ACE inhibitor captopril on the incidence and duration of reperfusion arrhythmias following experimentally induced myocardial ischemia in the isolated rat heart.* Acute regional ischemia was induced by ligation of the left coronary artery: kpefision was produced by releasing the ligation, thus prbvoking Ventricular arrhythmias. One group of rat hearts seyed as conttol; in the other, captopril 80 pg/ml was added to the perfusion injection at the start of the control penod. Treatment with captopril ?educed both the incidence and duktion of ventricular fibrillation. At the onset of reperfusion, all of the control hearts showed ventricular fibrillation, whereas ventricular filbrillation occurred in only 40% of captopri1;treated hearts (p
