The effect of nitric oxide synthase inhibitor on reperfusion injury of the brain under hypothermic circulatory arrest.
OBJECTIVE
The objective of this study was to investigate the protective effects of nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride, on reperfusion injury of the brain under hypothermic circulatory arrest.


METHODS
After cardiopulmonary bypass was established using 12 piglets each weighing about 30 kg, the animals were cooled to a brain temperature of 20 degrees C and circulatory arrest was performed for 90 minutes followed by reperfusion for 120 minutes. The level of nitric oxide within the brain was measured with a needle electrode inserted into the brain. In the treatment group, N(G)-nitro-L-arginine methyl ester hydrochloride was administered with an intravenous injection of 1.5 mg/kg at the onset of the reperfusion followed by a 60-minute continuous venous infusion of 1.5 mg/kg/hr.


RESULTS
In the control group, nitric oxide levels within the brain increased not during ischemia but during reperfusion, and the level after 120 minutes of reperfusion increased significantly compared with that of before circulatory arrest. But in the treatment group, N(G)-nitro-L-arginine methyl ester hydrochloride administered at the onset of reperfusion inhibited nitric oxide production during reperfusion. A significant difference was observed between the groups regarding the nitric oxide level after 120 minutes of reperfusion. Regarding cerebral blood flow, excess lactate, and cerebral tissue water content, no significant difference was observed between the groups. However, recovery of somatosensory evoked potential after 120 minutes of reperfusion was detected in all six animals in the treatment group, but none in the control group (p = 0.001).


CONCLUSIONS
These data suggest that N(G)-nitro-L-arginine methyl ester hydrochloride protects the brain against reperfusion injury under hypothermic circulatory arrest.
Segawa
D
D
Department of Surgery II, National Defense Medical College, Saitama, Japan.
Hatori
N
N
Yoshizu
H
H
Uriuda
Y
Y
Shimizu
M
M
Tanaka
S
S
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D005260:Female; D006324:Heart Arrest, Induced; D007036:Hypothermia, Induced; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013552:Swine; D013997:Time Factors
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester