Electrophysiological effects of diltiazem, nifedipine and Ni2+ on the subepicardial muscle cells of canine heart under the condition of combined hypoxia, hyperkalemia and acidosis.
Using microelectrode techniques, we examined the effects of the slow channel blockers diltiazem, nifedipine and Ni2+ on the tissue deterioration induced by a modified superfusion solution imitating some of the metabolic changes in acute myocardial ischemia (pO2 = 4.0--5.1 kPa, [K+] = 8 mmol/l, pH = 6.80) in the isolated right ventricular subepicardial muscles of canine heart. Resting membrane potential (RMP), action potential amplitude (APA), action potential duration and maximum upstroke velocity of action potential (V max) were reduced, and conduction time was prolonged during superfusion with the modified solution. In the presence of diltiazem (6.7 mumol/l), nifedipine (2.9 mumol/l) and Ni2+ (1.0 mmol/l), the degree of the reductions of APA and V max, and of the prolongation of conduction time induced by the modified solution was significantly reduced. However, none of the three slow channel blockers affected the change in RMP. These results suggest that decreasing calcium influx reduces the deteriorating effect of the modified solution on the sodium channels, and this action can partly explain the reduction of ischemia-induced conduction delay by slow channel blockers.
D000138:Acidosis / Q000503:physiopathology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006329:Heart Conduction System / Q000187:drug effects; D006947:Hyperkalemia / Q000503:physiopathology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D008297:Male; D009532:Nickel / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen
D001552:Benzazepines; D002121:Calcium Channel Blockers; D007473:Ion Channels; D009532:Nickel; D004110:Diltiazem; D009543:Nifedipine; D010100:Oxygen