Use of nifedipine to decrease ischemic-reperfusion injury in the surgical setting.
This report summarizes studies that provided a basis for a randomized clinical trial of nifedipine in cold hyperkalemic cardioplegic solution. Data from normothermic, isolated working rabbit heart studies demonstrated that presence of micromolar concentrations of nifedipine in the perfusate during continuous low flow or nifedipine used as bolus washouts during global ischemia prevented increases in systolic and diastolic stiffness, which could be related to dose and prevention of intracellular accumulation of calcium. Other studies in open-chest dogs in whom regional ischemia was produced showed that nifedipine was superior to sodium nitroprusside when infused during the ischemic and reperfusion intervals with respect to preservation of hemodynamic variables and reduction of myocardial injury. Further, data from cardiopulmonary bypass experiments in dogs conducted at myocardial temperatures of 37, 28, 18 and 12 degrees C with 1, 2 and 3 hours of global ischemia all demonstrated significant efficacy. To date, the randomized clinical trial has shown a small reduction in the incidence of low cardiac output syndrome in high-risk patients. Those receiving nifedipine had improved hemodynamic variables. No patient in the treated group had myocardial injury in the postoperative interval shown by radionuclide pyrophosphate scan. The conclusions from this trial are that nifedipine was efficacious when included in a cold hyperkalemic cardioplegic solution. The responses observed, however, appear to be dose-, vehicle- and species-dependent.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000503:physiopathology / Q000601:surgery; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced / Q000379:methods; D006349:Heart Valve Diseases / Q000503:physiopathology / Q000601:surgery; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology / Q000627:therapeutic use*; D010477:Perfusion; D011188:Potassium / Q000008:administration & dosage / Q000627:therapeutic use; D017680:Potassium Compounds; D011446:Prospective Studies; D011817:Rabbits; D011897:Random Allocation
D017680:Potassium Compounds; C018369:potassium cardioplegic solution; D009543:Nifedipine; D011188:Potassium