SOCIETY, TOLERANCE, AND EFFICACY OF ADENOSINE AS AN ADDITIVE TO BLOODCARDIOPLEGIA IN HUMANS DURING CORONARY-ARTERY BYPASS-SURGERY

Myocardial stunning after heart surgery is associated with increased m orbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluat e the safety, tolerance, and efficacy of adenosine as a cardioprotecti ve agent when added to blood cardioplegia in patients undergoing coron ary artery bypass surgery. Sixty-one patients were randomized to stand ard cold-blood cardioplegia, or cold-blood cardioplegia containing 1 o f 5 adenosine doses (100 mu M, 500 mu M, 1 mM, 2 mM, and 2 mM with a p reischemic infusion of 140 mu g/kg/min of adenosine). Invasive and non invasive measurements of ventricular performance and rhythm were obtai ned preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hour s postbypass. Use of inotropic agents and vasoactive drugs postoperati vely wets recorded; blood samples were collected for measurement of nu cleoside levels. High-dose adenosine treatment was associated with a 2 49-fold increase in the plasma adenosine concentration and a 69-fold i ncrease in the combined levels of adenosine, inosine, and hypoxanthine (p < 0.05). Increasing doses of the adenosine additive were also asso ciated with lower requirements of dopamine (p = 0.003) and nitroglycer ine (p = 0.001). The 24-hour average doses for dopamine and nitroglyce rine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose adenosine treatment cohorts. Finally, the placeb o- and 100 mu M-adenosine group was associated with a lower election f raction when compared to patients receiving the intermediate dose or h igh-dose treatment. These findings are consistent with the hypothesis that adenosine is effective in attenuating myocardial stunning in huma ns. (C) 1997 by Excerpta Medica, Inc.