The hypothesis tested in this study was that a new calcium channel blocker of the light, stable dihydropyridine series, nicardipine confers additional myocardial protection to a standard cardioplegic solution. Isolated working left hearts were used from rats at 37 and 10 degrees C, and dose response curves were developed. 27 and 210 minutes of ischemia were used, respectively. The data showed that a normothermia, a twofold increase in survival of the heart was achieved and performance of the hearts was doubled by use of the drug. No differences were found under cold conditions. It is postulated that the binding sites for this agent were minimized by hypothermia. These data confirm the efficacy of certain calcium channel blocking agents to ameliorate the ischemia reperfusion injury at normal temperatures but not a low temperatures. It was then postulated that nicardipine might work under hypothermic conditions if the animals were pretreated with the drug prior to the induction of hypothermic arrest. When the rats were pretreated with nicardipine 15 minutes prior to excision of their hearts significant improvement in post ischemic performance and conservation of high energy phosphates was demonstrated. This was dose dependent up to 25 micrograms/kg, with decreasing performance above that dose. Nicardipine is not clinically useful when added to cold cardioplegia but is useful when it is given prior to hypothermic ischemic arrest.
