Electrophysiologic and morphologic abnormalities in the failing heart: effect of enalapril on the electrical properties.
BACKGROUND
Knowledge of the electrophysiologic abnormalities in the failing heart is meager. In this work morphologic and electrophysiologic changes were investigated in the cardiomyopathic hamster (BIO TO-2) at 11 months of age. The results were compared with control hamsters (F1B) of the same age.


RESULTS
Conventional KCl microelectrodes were used to measure membrane potential, conduction velocity, and refractoriness. Histologic studies consisted of Harris' hematoxylin and eosin, Masson trichrome, and von Kossa's calcium stain. The resting potential of myopathic fibers (-67.8 mV; SEM 1 0.83) in the cardiomyopathic hamsters was less negative than the control subjects' potential (-78.5 V; SEM + 1), and the action potential duration measured at 50% of repolarization was increased by 213%. The conduction velocity (36.9 cm/s) was 15.7% lower than that of the control subjects. Enalapril (50 micrograms/mL) caused a hyperpolarization of 6.8 mV, it increased the action potential duration at 90% of repolarization by 110%, and the conduction velocity of the myopathic fibers was appreciably increased compared to the control hamsters'. The refractoriness of myopathic and normal ventricular fibers was also increased by enalapril. Histologic studies performed on the right and left ventricular wall indicated interstitial fibrosis, necrotic foci, and extensive calcification.


CONCLUSIONS
The results indicate severe morphologic and electrophysiologic abnormalities in the failing ventricular muscle. The effect of enalapril on membrane potential and conduction velocity might indicate that the activation of the cardiac renin-angiotensin system during the process of heart failure is, in part, responsible for the abnormalities described here. The improvement of impulse propagation and the increase in refractoriness seem to represent important factors involved in the antiarrhythmic action of enalapril.
De Mello
W C
WC
Department of Pharmacology, School of Medicine, University of Puerto Rico, San Juan 00936-5067.
Cherry
R C
RC
Manivannan
S
S
D000200:Action Potentials / Q000187:drug effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002303:Cardiac Output, Low / Q000473:pathology* / Q000503:physiopathology*; D006224:Cricetinae; D004594:Electrophysiology; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology; D006352:Heart Ventricles / Q000473:pathology; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D016276:Ventricular Function
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril