Preservation of myocardial high energy phosphates during cardioplegic arrest with nifedipine

Abstract

Nifedipine used both as an additive to cardioplegia solution (CPS) and as pretreatment prior to arrest was studied in a rat model to determine its effect upon ischemic ventricular electromechanical work during arrest and upon high energy phosphate levels. Fifty-one normothermic rats were studied in vivo with infusion of hypothermic (4°C) CPS into the cross-clamped aortic root according to one of the following eight protocols: Group 1, baseline beating hearts; Group 2, CPS containing 15 mEq potassium chloride/liter (KCl/liter); Group 3, CPS containing 30 mEq KCl/liter; Group 4, CPS containing 15 mEq KCl/liter combined with stimulation of the vagus nerve; Groups 5 and 6, CPS with 15 mEq KCl/liter and containing 250 or 500 μg of nifedipine per liter; Groups 7 and 8, pretreatment with 100 or 200 μg nifedipine/kg given as an intravenous bolus 15 min prior to infusion of CPS with 15 mEq KCl/liter. Time to arrest, number of ischemic ventricular contractions after aortic cross clamping, and ATP and creatine phosphate (CP) levels were recorded. All nifedipine groups arrested more quickly and with fewer ventricular contractions and had ATP and CP levels higher than those of Group 2 ( P < 0.05). There were no differences between the nifedipine groups and Group 3 except that Group 8 (200 μg/kg pretreatment) resulted in higher levels of CP than Groups 3, 5, and 6 ( P < 0.05 for all groups). When all groups were combined, time to arrest correlated negatively with ATP ( r = −0.863, P < 0.01) and CP ( r = −0.824, P < 0.01) levels. The number of ventricular contractions after aortic cross-clamping also correlated negatively with ATP ( r = −0.896, P < 0.01) and CP ( r = −0.830, P < 0.01) levels. CP was depleted 1.5 to 1.6 times as rapidly as ATP. We conclude that (1) there is a direct relationship between ischemic electromechanical work and myocardial energy stores during cardioplegic arrest, (2) CP is a more sensitive index of myocardial energy depletion than ATP, and (3) pretreatment with nifedipine prior to cardioplegic arrest results in greater preservation of myocardial energy stores than that obtained with CPS containing potassium alone or with the addition of nifedipine.