Nitric oxide synthase inhibition by l-name during repetitive focal
cerebral ischemia in rabbits.
Anderson, Robert E., Fredric B. Meyer, Thoralf M. Sundt.
Neurosurgical Research Laboratory, Mayo Clinic and Mayo Graduate
School of Medicine, Rochester, Minnesota, USA
APStracts 3:0069H, 1996.
The effects of nitric oxide synthase (NOS) inhibition on brain
acidosis, regional cortical blood flow (rCBF), and NADH redox state
using in vivo fluorescence imaging were examined during four 15
-minute periods of moderate focal cerebral ischemia, each separated by
three 5-minute reperfusion periods followed by a final 3- hour
reperfusion period. Fasted rabbits under 1.5% halothane, were divided
into 6 groups of 7?animals each: 1) non-ischemic controls; 2)
ischemic controls; and the following drug groups receiving L-NAME
intravenously, twenty minutes prior to repetitive ischemia: 3) 0.1
mg/kg; 4)?1?mg/kg; 5)?10?mg/kg; and 6)?1?mg/kg + 5 mg/kg L-arginine.
L-NAME at 0.1 and 1.0 mg/kg prevented the development of significant
brain acidosis throughout the four ischemic insults. L-NAME at 10.0
mg/kg reduced preischemic rCBF by 21% (p<0.05) and did not
mitigate brain acidosis after the third and forth ischemic insults.
Brain pHi returned towards baseline following the 3-hour final
reperfusion in all groups. NADH redox state was significantly
(p<0.05) elevated from baseline controls in all groups during
the last three ischemic insults. During the final reperfusion period,
NADH redox state returned towards baseline values only with the 0.1
mg/kg L-NAME and ischemic control group. In conclusion low dose L
-NAME attenuated brain acidosis independent from rCBF changes during
intermittent moderate focal cerebral ischemia.
Received 10 September 1995; accepted in final form 26 January
1996.
APS Manuscript Number H850-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 14 February 96