Effect of ryanodine on the initiation and perpetuation of stretch-induced arrhythmias in isolated canine ventricle.
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)
Jobe
R L
RL
Division of Cardiology, Vanderbilt University Medical School, Nashville, Tennessee 37232.
Taylor
L K
LK
Wang
Z
Z
Berger
C M
CM
Stacy
G P
GP
Hansen
D E
DE
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D005117:Cardiac Complexes, Premature / Q000503:physiopathology; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles; D066298:In Vitro Techniques; D010477:Perfusion; D011336:Probability; D012433:Ryanodine / Q000494:pharmacology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013314:Stress, Mechanical; D013327:Strophanthidin / Q000494:pharmacology; D013997:Time Factors
D012433:Ryanodine; D013327:Strophanthidin; D002118:Calcium