PREVENTION OF SOME HYPOTHERMIA INDUCED ELECTROMECHANICAL CHANGES BY CALCIUM-CHANNEL BLOCKADE

Objective: Cooling induces electromechanical changes in the heart. The aim of the study was to examine how the calcium channel blocker, nisoldipine (NIS), altered these changes compared to those induced by other drugs that shorten action potential duration such as tetrodotoxin and nicorandil. Methods: Guinea pig papillary muscle action potentials and developed force were recorded using the conventional microelectrode technique and a force transducer. Restitution of action potential duration was determined by introducing extra stimuli at progressively longer diastolic intervals from 40 to 9000 ms. Preparations were divided into four groups: (1) no drug (control); (2) 1 muM tetrodotoxin, a sodium channel blocker; (3) 1 mM nicorandil, an ATP sensitive potassium channel activator; and (4) 1 muM nisoldipine (n = 6 in each group). Action potential duration and developed force were recorded after addition of drug at 37-degrees-C, and at each 1-degrees-C change in temperature during cooling to 27-degrees-C. The restitution protocol was performed at 37-degrees and 27-degrees-C. Results: Tetrodotoxin had no effect on action potential duration at 90% of repolarisation (APD90) while nisoldipine and nicorandil greatly shortened APD90. Cooling from 37-degrees to 27-degrees-C with nisoldipine produced less hypothermia induced lengthening in APD90 than in the other group. Developed force did not increase with reduction in temperature in the presence of nisoldipine. The range of premature action potential durations was defined as the difference in APD90 at diastolic interval of 40 and 100 ms. This range decreased with nisoldipine in contrast to the marked increases that occurred in the other groups during cooling. Conclusions: Increased intracellular Ca2+ might be responsible for the hypothermia induced increase in APD90, developed force, and range of premature action potential durations, since calcium channel blockade, which prevents an increase in intracellular Ca2+, greatly reduced these changes. The reduced range of premature action potential durations may reduce dispersion of ventricular refractoriness, and hence be expected to decrease hypothermia induced arrhythmias.