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