Augmentation of microvascular nitric oxide improves myocardial performance following global ischemia.
Hearts exposed to global myocardial ischemia associated with cardiac surgery often suffer postischemic endothelial and contractile dysfunction related to antecedent regional or global ischemia. Our studies tested the hypothesis that supplementing blood cardioplegia and reperfusion with the nitric oxide (NO) precursor L-arginine or the NO donor SPM-5185 would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction or global dysfunction. In the first study involving 23 anesthetized dogs undergoing regional ischemia, supplementation of blood cardioplegia with L-arginine: (1) reduced infarct size; (2) improved postischemic regional segmental work and diastolic stiffness; (3) attenuated neutrophil accumulation in the area at risk; and (4) improved postischemic depressed coronary artery endothelial function. The NO synthase inhibitor N-nitro-L-arginine (L-NA) reversed these protective effects. In another experiment involving 18 anesthetized dogs undergoing normothermic global ischemia, hearts treated with blood cardioplegia supplemented with the NO donor SPM-5185 demonstrated better postischemic coronary artery endothelial function, lowered myeloperoxidase activity in the ischemic-reperfused myocardium, and significantly improved global ventricular function in the group receiving high-dose SPM-5185. We conclude that the inclusion of L-arginine or high-dose NO donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly by inhibition of neutrophil-mediated damage via the L-arginine-NO pathway.
Hammon
J W
JW
Department of Cardiothoracic Surgery, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1096, USA.
Vinten-Johansen
J
J
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology / Q000627:therapeutic use; D016276:Ventricular Function
D004151:Dipeptides; C076992:N-nitratopivaloyl-S-(N'-acetylalanyl)-cysteine ethyl ester; D009569:Nitric Oxide; D001120:Arginine