Increasing nitric oxide production improves survival in experimental hemorrhagic shock.
The purpose of this study was to evaluate the importance of nitric oxide (NO) upon outcome following hemorrhagic shock. L-Arginine, an NO precursor, and L-NMMA, an inhibitor of NO synthesis, were added to resuscitation in a prospective, randomized, and double-blinded experimental model, and the effects upon blood pressure and survival were measured.


METHODS
60 Sprague-Dawley rats were anesthetized and subjected to phlebotomy to induce hemmorrhagic shock. After a 45 min shock period, animals were resuscitated with either lactated Ringer's alone (control), L-NMMA in lactated Ringer's or L-arginine in lactated Ringer's. Blood pressure was monitored, and animals were observed for survival. As an additional control experiment, 15 additional animals underwent the same protocol, but underwent sham shock, i.e. were not haemorrhaged.


RESULTS
L-NMMA increased blood pressure transiently following sham shock, but increased blood pressure to a greater extent and for a longer duration following hemorrhage. However, L-NMMA had no effect upon survival. L-Arginine had no measurable effect upon blood pressure, but significantly increased survival.


CONCLUSIONS
NO may play an important role following hemorrhage. The effectiveness of L-NMMA as a pressor suggests that NO contributes to hypotension following hemorrhage. However, reversing hypotension with L-NMMA did not improve survival in this model. In contrast, L-arginine did not further lower blood pressure, but had significant survival benefit. This suggests a possible protective effect of NO after hemorrhage, perhaps by improving the distribution of capillary blood flow and/or by decreasing platelet aggregation and leukocyte adhesion within the microcirculation.
Daughters
K
K
Department of Surgical Education, Santa Barbara Cottage Hospital, CA 93102, USA.
Waxman
K
K
Nguyen
H
H
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine