Ischemia-reperfusion induced elevation of diastolic tension in the isolated guinea pig heart and the effects of calcium antagonists.
Characteristics of the temporal elevation of diastolic tension, produced by ischemia-reperfusion in isolated and paced Langendorff's hearts of guinea pigs, were studied. The elevation of diastolic tension corresponded with an elevation of left ventricular end diastolic pressure after a short ischemic period in the isovolumic heart. These phenomena were thought to be a result of incomplete relaxation. The degree of the elevation of diastolic tension depended upon the duration of ischemic period (3-10 min). This elevation was reproducible in one preparation; nearly the same changes were obtained in a second trial after 35 min of reperfusion when the ischemic period was within 5 min. An increment in the pacing rate to 150% of the first trial value doubled the elevation of diastolic tension by the second 5 min ischemia. Inhibition of glycolytic flux by iode acetic acid augmented the elevation after 3 min of ischemia. In addition, 5 min of ischemia with iode acetic acid caused contracture and recovery was slight. On the other hand, either lowering the Ca2+ concentration in the perfusing solution to a half the normal value, or treatment with Ca2+ antagonists (such as diltiazem), reduced the elevation of diastolic tension significantly. Diltiazem also suppressed the increment in elevation produced by a high pacing rate. It can be concluded that the temporal elevation of diastolic tension during reperfusion reflects the ischemic failure of the heart. This change is presumably due to intracellular Ca2+ overload or accumulation. In addition, since ischemic changes were reproducible in this preparation, it is a useful model for estimating the effects of drugs on the ischemic heart.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D003971:Diastole / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007461:Iodoacetates; D014700:Verapamil; D004110:Diltiazem; D019807:Iodoacetic Acid