We assessed the influence of the prophylactic use of a combination of the IV beta-adrenergic blocker, esmolol, and the phosphodiesterase III inhibitor, enoximone, on postbypass hemodynamic status, inflammation, and endothelial and organ function in a prospective, randomized, placebo-controlled study in 42 patients aged >65 yr undergoing aortocoronary bypass grafting. In 21 patients, esmolol (aim: heart rate <70 bpm) plus enoximone (initial bolus of 0.5 mg/kg followed by a continuous infusion of 2.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and continued until the morning of the first postoperative day; another 21 patients received saline solution as placebo. Hemodynamics, splanchnic perfusion (gastric-arterial CO(2) gap), liver function (glutathione transferase-alpha plasma levels), renal function (creatinine clearance, urine concentrations of N-acetyl-beta-D-glucosaminidase), myocardial ischemia (creatine-kinase MB and troponin T plasma levels), inflammation (elastase, interleukin-6 and -8 plasma levels), and endothelial integrity (adhesion molecules plasma levels) were assessed at baseline, before and after cardiopulmonary bypass (CPB), and in the intensive care unit until the first postoperative day. Catecholamine requirements were significantly less in the treated than in the nontreated patients. Heart rate was significantly slower, cardiac index was higher, and gastric-arterial CO(2) gap was significantly lower in the treatment group. Troponin T, beta-N-acetyl-beta-D-glucosaminidase, glutathione transferase-alpha, and soluble adhesion molecules increased significantly in the untreated control, but remained almost normal in the esmolol+enoximone patients. Inflammatory responses (elastase/interleukins) were attenuated by esmolol+enoximone. We conclude that, in comparison to an untreated control, the prophylactic use of a combination of esmolol and enoximone in elderly patients undergoing cardiac surgery with cardiopulmonary bypass resulted in overall beneficial effects on postbypass hemodynamic status, organ function, inflammatory response, and endothelial integrity.