ABSTRACT
BACKGROUND: Levosimendan, an inotropic drug that enhances myocardial contractility through myofilment calcium sensitazion, induces peripheral vasodilation via opening ATP-dependent K(+) channels. It is unknown whether this drug can be used for the treatment of perioperative vasospasm of arterial conduits used for coronary artery bypass grafting. METHODS: We investigated the effects of levosimendan on human internal mammary artery (IMA) specimens taken from patients undergoing coronary artery bypass surgery. The rings were carefully prepared and placed between two wire hooks in organ bath chambers and then constricted submaximally with norepinephrine and thromboxane A(2) analog (U46619). Nitroglycerin, milrinone, and levosimendan were separately added in a cumulative fashion and concentration response curves for relaxation were constructed. In parallel experiments, the response to levosimendan was evaluated on rings with and without functional endothelium. Levosimendan prevention of norepinephrine-induced contraction was also estimated. RESULTS: Nitroglycerin, milrinone, and levosimendan completely reversed the contraction of the IMA segments induced by U46619 and norepinephrine. Levosimendan produced a potent, concentration-dependent preventive effect on the norepinephrine-induced contraction of IMA. The responses to levosimendan were similar in preparations with or without endothelium.
Subject(s)
Hydrazones/pharmacology , Mammary Arteries/drug effects , Pyridazines/pharmacology , Vasodilation/drug effects , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Mammary Arteries/physiology , Simendan , Vasodilation/physiology , Vasodilator Agents/pharmacologyABSTRACT
OBJECTIVE: To investigate how off-pump coronary artery bypass grafting (CABG) affects postoperative pulmonary function when compared with on-pump CABG. DESIGN: Prospective clinical study. SETTING: University-affiliated teaching hospital. PARTICIPANTS: Adult patients (n = 39) undergoing elective coronary artery bypass surgery with or without cardiopulmonary bypass. INTERVENTIONS: Two groups of patients were compared: 19 consecutive patients undergoing off-pump CABG surgery and 20 consecutive patients undergoing conventional CABG surgery. MEASUREMENTS AND MAIN RESULTS: Pulmonary function tests (flow volume loops and lung volumes with plethysmography) were done preoperatively and 72 hours postoperatively. Arterial blood gases and PaO2/FIO2 were measured at various stages. Sequential chest x-rays were obtained and evaluated for pleural changes, pulmonary edema, and atelectasis. In both groups, PaO2/FIO2 ratios decreased progressively throughout the perioperative period, with no significant differences between the groups at any stage during the study. There was a significant decline in postoperative pulmonary function tests in both groups, but there was no difference between groups at 72 hours postoperatively. No differences were found in the time to extubation, atelectasis scores, or postoperative complications. CONCLUSIONS: Off-pump CABG does not confer major protection from postoperative pulmonary dysfunction compared with CABG surgery with CPB. Strategies for minimizing pulmonary impairment after CABG surgery should be directed to factors other than the use of CPB.