AJP - Heart and Circulatory Physiology, Vol 267, Issue 5 1736-H1744, Copyright © 1994 by American Physiological Society
Effect of ryanodine on the initiation and perpetuation of stretch-induced arrhythmias in isolated canine ventricle
R. L. Jobe, L. K. Taylor, Z. Wang, C. M. Berger, G. P. Stacy Jr and D. E. Hansen
Division of Cardiology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
Ventricular arrhythmias can be initiated by a mechanism of transient
diastolic dilation. To test the hypothesis that Ca2+ release from
sarcoplasmic reticulum (SR) is important in initiation of such
stretch-induced arrhythmias (SIAs), we studied effects of ryanodine in an
isolated canine heart model. Arrhythmias were induced by a computerized
ventricular volume servo-pump system that transiently increased left
ventricular volume by precise amounts (delta V) during diastole. The
probability of eliciting an SIA (PSIA) was compared at the minimum delta V
that resulted in PSIA of > or = 90% under baseline conditions. Block of
SR Ca2+ release with 10(-5) M ryanodine in 11 ventricles produced mild
inhibition of SIAs, reducing PSIA by 19.4% (P = 0.039). Because ryanodine
produces leakage of SR Ca2+ at low concentration and block of SR Ca2+
release at high concentration, ryanodine concentration was varied from
10(-9) to 10(-5) M in six ventricles. Ryanodine had minimal effect on PSIA
over this concentration range. In six ventricles with elevated
intracellular Ca2+ produced by pretreatment with 0.1-0.3 microM
strophanthidin, 10(-5) M ryanodine did not significantly reduce PSIA.
Probability of inducing ventricular pairs or nonsustained ventricular
tachycardia was greater in strophanthidin-treated ventricles than in
controls, but induction of these repetitive ventricular beats in the
strophanthidin group was virtually abolished by addition of 10(-5) M
ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
