Effects of coronary flow, pacing rate, isoprenaline and diltiazem on ischemic ventricular arrhythmias in guinea pig hearts.
Although the Ca++ channel blockers can reduce early ischemic ventricular arrhythmias, the mechanisms are unclarified. The antiarrhythmic action of Ca++ antagonists may either be due to vasodilation and negative chronotropism or to trans-sarcolemmal Ca++ influx inhibition. In these studies we investigated the possible individual and additive effects of coronary flow, heart rate and Ca++ antagonism on ventricular arrythmia development in isolated, paced, globally underperfused guinea pig hearts. When the coronary flow during ischemia was raised from 5 to 7% of control and/or the stimulation frequency was decreased from 6 to 4 Hz, ATP and creatine phosphate levels were conserved and intraventricular conduction slowing leading to ventricular tachycardia (VT) was delayed. In contrast, when the coronary flow and pacing rates were fixed at 7% and 6 Hz and diltiazem (10(-6) M) was included in the perfusion medium, there was no effect on tissue high-energy phosphate depletion and development of VT. Even when the breakdown of ATP and the onset of VT were accelerated by isoprenaline (10(-6) M), diltiazem was not antiarrhythmic at this flow rate. Only when the coronary flow was reduced to 5% of control, in the absence and presence of isoprenaline, did diltiazem delay ventricular arrhythmias through a mechanism that was independent of changes in coronary flow and heart rate.
Dennis
S C
SC
Ischemic Heart Disease Research Unit, University of Cape Town Medical School, Observatory, South Africa.
Coetzee
W A
WA
de Jong
J W
JW
Clusin
W
W
Opie
L H
LH
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000032:analysis; D003326:Coronary Circulation; D003327:Coronary Disease / Q000150:complications*; D004110:Diltiazem / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011687:Purines / Q000378:metabolism
D011687:Purines; D004110:Diltiazem; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium