Preconditioning of Ischemic Myocardium via Involvement of the L-arginine/Nitric Oxide Synthase Pathway

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Houshyar, Hani
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The objective of this investigation was to evaluate involvement of the L-arginine/ nitric oxide synthase pathway in myocardial ischemic preconditioning as assessed by myocardial infarct size. Using New Zealand White rabbits, the nitric oxide precursor, L-arginine, was administered alone or in conjunction with the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). These animals were compared to ones treated with the saline vehicle, D-arginine, or L-NAME only. Systemic hemodynamics, including heart rate, arterial and left ventricular pressures, and myocardial contractility (LV +dp/dt max) were monitored throughout each experiment. A branch of the left main coronary artery was occluded for 30 min, followed by 120 min of reperfusion. The saline vehicle, D-arginine, or L-arginine were administered as 5 min intraventricular infusions, followed by 10 min of recovery period prior to the sustained occlusion. Intravenous administration of L-NAME was carried out for 90 min prior to brief intraventricular infusion of either the saline vehicle or L-arginine. Systemic hemodynamics were not significantly different from control in most cases, except for the development of a moderate depression of heart rate, mean arterial pressure, and myocardial contractility which occurred in both treatment groups receiving L-NAME. A modest though significant myocardial contractile depression was noted in the L-arginine group, while a transient increase of left ventricular end diastolic pressure was observed in the saline vehicle group. Myocardial area at risk was not significantly different among treatment groups. Brief infusion of exogenous L-arginine to simulate preconditioning significantly reduced infarct size below the saline vehicle treatment group This cardioprotective effect of L-arginine was abolished as a result of administration of L-NAME prior to L-arginine infusion. Neither D-arginine nor L-NAME only infusions significantly altered the degree of infarction compared to the saline vehicle group. Thus, these results suggest the L-arginine/NO pathway may be a physiological mediator of the endogenous protective mechanisms involved in myocardial preconditioning. However, further investigations are necessary to determine the exact involvement of this pathway in ischemic preconditioning.
vi, 30 p.
Kalamazoo College
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