Protection by verapamil of globally ischemic rat hearts: Energy preservation, a partial explanation

Abstract

The relationship between energy preservation and the recovery of heart function was studied in globally ischemic hearts which were treated with verapamil. Isolated working rat hearts reperfused after 27 min of ischemia recovered 17.9 +/- 5.11% of pre-ischemic contractile function and had markedly reduced tissue ATP, total adenine nucleotide, and creatine phosphate levels. The ATP/ADP ratio was also decreased in these hearts. When verapamil (2 X 10(-6) M) was present before and during ischemia, but not during reperfusion, the recovery of cardiac function following reperfusion was improved (82.4 +/- 12.1%). When hearts were treated with 0.0, 7.5 X 10(-8) M, 5 X 10(-7) M, or 2 X 10(-6) M verapamil, the recovery of cardiac function was proportional to the concentration of verapamil present and showed a linear relationship with the depression of cardiac function prior to ischemia. The ATP, total adenine nucleotide and creatine phosphate levels were significantly higher in those hearts which were treated with verapamil, but the increase was not proportional to the recovery of cardiac function. It is possible that a critical pool of ATP may correlate with the recovery of verapamil treated hearts, but a large degree of mechanical recovery occurred with significant loss of high energy phosphate stores. Thus, while high energy compounds were preserved, there was not a good correlation between recovery of cardiac function and the preservation of total tissue energy reserves. A portion of the protection afforded by verapamil to globally ischemic hearts may be due to energy preservation, but additional mechanisms may also be involved in the enhanced recovery of contractile function.