Preconditioning of Ischemic Myocardium via Involvement of the L-arginine/Nitric Oxide Synthase Pathway
Loading...
Authors
Houshyar, Hani
Issue Date
1994
Type
Thesis
Language
en_US
Keywords
Alternative Title
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.
Description
vi, 30 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.