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2008, Number 4

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Cir Cir 2008; 76 (4)

Exogenous nitric oxide donor in the liver inflammatory and hemodynamic response after hemorrhagic shock

Anaya-Prado R, Toledo-Pereyra LH, Ren-Feng G, Reuben J, Ward PA

Language: Spanish
References: 31
Page: 291-298
PDF size: 121.71 Kb.


ABSTRACT

Background: Hemorrhagic shock (HS) results in oxidative stress to cells and in the induction of the inflammatory response. We tested the ability of the nitric oxide (NO) donor sodium nitroprusside (NP) to reduce tissue injury in a rodent model of uncontrolled hemorrhagic shock.
Methods: Seventy two Sprague Dawley rats weighing 250-300 g were subjected to a model of uncontrolled hemorrhagic shock. Four groups of animals were included (n = 18 per group): sham/saline, sham/NP, shock/saline, shock/NP. Experimental design consisted of the development of hemorrhagic shock (3 ml/100 g) in a 15-min period, tail amputation (75%) and drug administration at 30 min, fluid resuscitation (FR) with lactate Ringer’s (LR) solution to reach a mean arterial pressure (MAP) of 40 mmHg, a hospital phase of 60 min with hemostasis and FR with LR solution to reach a MAP of 70 mmHg, and a 3-day observation phase. Treatment at the beginning of resuscitation included either normal saline or sodium nitroprusside (0.5 mg/kg). The following parameters were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase (MPO), liver histology, and 3-day survival.
Results: Sodium nitroprusside significantly reduced fluid requirements for resuscitation (p = 0.0001). We also observed an improved statistically significant difference in tests demonstrating hepatic injury (p = 0.0001), neutrophil infiltration as evidences by liver MPO (p ‹0.05), and histology studies (p = 0.001). Survival was also increased from 40% in controls to 60% with NP treatment.
Conclusions: These data suggest that excess NO mediates hemorrhage-induced liver injury, and that the suppression of NO with NP may reduce the pathological consequences of severe hemorrhage, possibly by scavenging superoxide (O2–), thus limiting the production of more aggressive radicals.


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