Dependence of myocardial hypothermia tolerance on sources of activator calcium

To determine the relationship between cardiac hypothermia tolerance and the sources of activator calcium, we selectively modified either the sarcolemmal calcium permeability by nifedipine or the sarcoplasmic reticulum function by caffeine in papillary muscles from both the rat, as a cold sensitive model, and the ground squirrel, Citellus dauricus, a deep hibernator. Both force-interval relationship and cooling performance were investigated. At 25 degrees C, the slope of the force-interval curve of the ground squirrel was nearly double that of the rat. At shorter test intervals 0.5 muM nifedipine moved the curve down with little effect at longer intervals, and the curve slope increased. Caffeine (1 mM) decreased the peak force and eliminated its dependence upon test interval. When the temperature was lowered, rat preparations showed a marked increase of resting tension and aftercontraction between 7 and 12 degrees C and became inexcitable. In contrast, they maintained contractility down to a few degrees above 0 degrees C without aftercontraction and increased resting tension in the ground squirrel. In the rat nifedipine shortened the contractions, prevented the increase of resting tension, and minimized aftercontractions, with little improvement of contractility. Caffeine prolonged the contractions, caused a striking increase of resting tension and aftercontractions, and finally disabled the contractility at about 5-10 degrees C, even in the ground squirrel. We conclude that depressed calcium influx helps to prevent hypothermic calcium overload of the cardiac cells. Good function of the sarcoplasmic reticulum is essential for tolerance of hypothermia by cardiac cells. A suggestion that may improve the hypothermic tolerance of the myocardium from nonhibernators is postulated.