Myocardial stunning after heart surgery is associated with increased morbidity and mortality in patients with severe multivessel disease and reduced myocardial function. The purpose of this study was to evaluate the safety, tolerance, and efficacy of
adenosine as a
cardioprotective agent when added to blood
cardioplegia in patients undergoing
coronary artery bypass surgery. Sixty-one patients were randomized to standard cold-blood
cardioplegia, or cold-blood
cardioplegia containing 1 of 5
adenosine doses (100 microM, 500 microM, 1 mM, 2 mM, and 2 mM with a preischemic infusion of 140 microg/kg/min of
adenosine). Invasive and noninvasive measurements of ventricular performance and rhythm were obtained preoperatively, prebypass, and then at 1, 2, 4, 8, 16, and 24 hours postbypass. Use of inotropic agents and vasoactive drugs pastoperatively was recorded; blood samples were collected for measurement of
nucleoside levels. High-dose
adenosine treatment was associated with a 249-fold increase in the plasma
adenosine concentration and a 69-fold increase in the combined levels of
adenosine,
inosine, and
hypoxanthine (p <0.05). Increasing doses of the
adenosine additive were also associated with lower requirements of
dopamine (p = 0.003) and nitroglycerine (p = 0.001). The 24-hour average doses for
dopamine and nitroglycerine in the placebo group were 28-fold and 2.6-fold greater than their respective high-dose
adenosine treatment cohorts. Finally, the placebo- and 100 microM-
adenosine group was associated with a lower ejection fraction when compared to patients receiving the intermediate dose or high-dose treatment. These findings are consistent with the hypothesis that
adenosine is effective in attenuating
myocardial stunning in humans.