title: Differing electrophysiologic effects of slow response inhibiting agents manganese and verapamil on ischemic, infarcted and normal tissue in situ.
abstract: To determine the electrophysiologic effects of slow response inhibiting agents manganese (Mn) and verapamil, we performed intracoronary infusion of these agents into ischemic, normal and infarcted tissue of canine hearts in situ. We determined intramyocardial conduction intervals, effective refractory period (ERP) and mean femoral arterial pressure. We compared control infusions of isotonic sucrose alone to those in which Mn (0.6 mmol/min) or verapamil (10-20 micrograms/min) was infused into ischemic tissue in the first 10 min after left anterior descending coronary artery ligation. We also studied infarcted tissue 1 hr after coronary artery ligation (Mn only) and normal tissue. During ischemia, Mn delayed conduction intervals in the subepicardium but not in the subendocardium and shortened subepicardial ERP. Mn also increased the occurrence of ventricular fibrillation during ischemia. In infarcted tissue, Mn had no effects on conduction intervals or ERP while in normal tissue it also had no effect on conduction interval but prolonged ERP. Verapamil had no effect on conduction intervals or ERP in ischemic or normal tissue. Neither Mn nor verapamil had any significant effects on mean blood pressure in these studies. Lack of effect of verapamil in ischemic tissue may be explained by the varying and offsetting effects of this drug. Effects of Mn can be explained by slow response occurring during ischemia (when ventricular arrhythmias and increased local potassium concentration occur) in ischemic epicardium but not in endocardium and not when tissue became infarcted (and ventricular arrhythmias have declined). The results are also consistent with our finding that delayed electrical activity in ischemic zones (which may reflect reentrant activity and be associated with arrhythmias) occurred only in subepicardium and not in subendocardium.
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D008345:Manganese / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000503:physiopathology; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013395:Sucrose / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D008345:Manganese; D013395:Sucrose; D014700:Verapamil