The effect of nitric oxide synthase inhibition upon post-ischemic
cerebral hyperemia.
Greenberg, Robert S., Mark A. Helfaer, Jeffrey R. Kirsch, Richard J.
Traystman.
Department of Anesthesiology and Critical Care Medicine, The Johns
Hopkins Medical Institutions, Baltimore, Maryland, 21287 USA
APStracts 2:0085H, 1995.
We tested the hypothesis that inhibition of nitric oxide synthase
(NOS) activity in brain before ischemia decreases postischemic
hyperemia. Pentobarbital anesthetized piglets underwent 15 minutes of
complete global cerebral ischemia induced by elevation of
intracranial pressure followed by 20 minutes of reperfusion. Prior to
ischemia the animals were randomly assigned to receive either
intravenous N_-nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n=6 or
50 mg/kg, n=6) or an equal volume of saline (10 ml, n=8). Serial
cerebral blood flow (radiolabeled microspheres) was measured at
baseline and during ischemia and reperfusion. Forebrain postischemic
hyperemia was documented after administration of saline (42+/-4 to
88+/-10), 10 mg/kg L-NAME (36+/-4 to 59+/-9), but not after 50 mg/kg
L-NAME (29+/-3 to 34+/-7 ml/min/100g). However, the percent reduction
in cerebral vascular resistance (CVR) fell during reperfusion to a
similar extent in all three groups, because of differences between
groups in cerebral perfusion pressure changes during the protocol.
CVR fell to the lowest level at 8 minutes reperfusion in the saline
treated animals (2.0+/-0.16 to 0.68+/-0.05 mm Hg/ml/min/100g)
compared with the L-NAME treated animals (50 mg/kg; 4.0+/-0.3 to
1.8+/-0.2 mm Hg/ml/min/100g). Brain NOS activity increased over time
in the saline treated animals (n=4, max 152+/-29% of baseline at 15
minutes) but decreased in a dose-related manner after 10 mg/kg (n=4,
59+/-27% of baseline at 15 minutes) and 50 mg/kg L-NAME (n=5, 10+/-3%
of baseline at 15 minutes). These results suggest that inhibition of
NOS with L-NAME has an effect on early (< 8 mins) post-ischemic
vasodilation, but is unlikely that nitric oxide is the sole mediator
for postischemic hyperemia beyond 8 minutes of reperfusion.
Received 5 August 1994; accepted in final form 25 January 1995.
APS Manuscript Number H701-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.