AJP - Heart and Circulatory Physiology, Vol 258, Issue 1 17-H23, Copyright © 1990 by American Physiological Society
Protection by benzamil against dysfunction and damage in rat myocardium after calcium depletion and repletion
G. N. Pierce, T. G. Maddaford, E. A. Kroeger and E. J. Cragoe
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Perfusion of the rat right ventricular wall muscle for 4 min with a
Ca2(+)-free medium followed by perfusion with a Ca2(+)-containing solution
resulted in a 42% recovery of developed tension, contracture, and a massive
release of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH)
from the muscle. High concentrations (1-5 mM) of amiloride partially
protected the ventricular wall from Ca2+ paradox-induced dysfunction. The
inclusion of benzamil, an amiloride analogue, 2 min before and during the
Ca2(+)-free perfusion period prevented contracture development, restored
force development, and almost totally eliminated the release of CPK and LDH
from the muscle. Contractile function was best protected by 10-50 microM
benzamil. The results demonstrate the efficacy of benzamil as a protective
agent against Ca2+ paradox-induced myocardial dysfunction and damage. In
view of the known capacity of benzamil to block transsarcolemmal Na(+)-Ca2+
exchange, this study supports the involvement of elevated intracellular Na+
and a stimulation of Na(+)-Ca2+ exchange in this model of cardiac
pathology.
