Experimental study of myocardial protection using calcium antagonist

The protective effect of a calcium antagonist on reperfused myocardium was investigated, with particular reference to cardiac sarcoplasmic reticulum (SR). SR function, which is closely related to cardiac diastolic function, was measured before and after coronary reflow. Verapamil (2mg/L), a calcium antagonist, was added to a cardioplegic solution, and its protective effect against SR injury was compared with that of potassium (K+, 20mEq/L) by measurement of SR function and cardiac functions.In 7 dogs, the left ventricular myocardium was resected to prepare SR for measurement of its Ca2+-binding function as a control. Another 24 canine hearts were placed on cardiopulmonary bypass (CPB). Then, intermittent aortic root infusion of each cardioplegic solution (0°C, pH 7.40, 360mOsm/L) was performed during 2 hours of aortic clamping. The myocardial temperature was kept at 15±3°C. After 2 hours of ischemia with either verapamil solution (Group I-A: n=5) or potassium solution (Group II-A: n=5), each myocardium was resected before reperfusion, and SR was prepared for measurement of its Ca2+-binding function. Fourteen canine hearts, which were protected with either verapamil solution (Group I-B: n=7) or potassium solution (Group II-B: n=7), were reperfused and cardiac functions were measured for 60 minutes after weaning from CPB. Then, the Ca2+-binding function of SR prepared from each reperfused myocardium was measured.With regard to Ca2+-binding function of SR, there was no significant difference between Group I-A and Group II-A, but a significant decrease was seen in Group II-B compared with Group II-A and Group I-B. There was no difference in contractility between Group I-B and Group II-B, but performance and diastolic parameters, especially the time constant T, were well preserved in Group I-B compared with Group II-B.It was concluded that after 2 hours of global ischemia of the myocardium, SR function was well preserved with verapamil and potassium. After reperfusion, SR function was impaired in both groups, but verapamil preserved SR function better than potassium. Therefore, cardiac functions, especially performance and diastolic parameters, appeared to be well preserved with verapamil. These results suggest that SR injury after reperfusion can be reduced with calcium antagonists.