• Hae W Kim and A Gerson Greenburg.
• Department of Surgery, Brown University and The Miriam Hospital, Providence, Rhode Island 02906, USA.
• Shock. 2002 May 1;17(5):423-6.

AbstractElevated levels of nitric oxide (NO) may be a primary cause of the vascular hyporeactivity (vasoplesia) and refractory hypotension in sepsis. This study was initiated to determine the efficacy of NO scavenging with acellular hemoglobin (Hb) solution in modulating sepsis-mediated vasoplesia. Male Sprague Dawley rats were subjected to sepsis by cecal ligation and puncture (CLP). Twenty-four hours post-CLP, the animals were randomly assigned to one of four groups (n = 5-6 each) and given an intravenous injection of 0.5 mL bovine serum albumin (BSA; 5 g/dL), 0.5 mL human Hb (7g/dL), 50 microL Nomega-nitro L-arginine methyl ester (NAME; 1 M), or both Hb and NAME. Blood pressure (BP), cardiac output, systemic vascular resistance, and vascular reactivity (VR) to norepinephrine (NE; 40 ng/Kg) were assessed before and after an experimental treatment. In some animals, inducible NO synthase (iNOS) mRNA expression was assessed in selected tissue samples harvested at the conclusion of experiment using a reverse transcription-polymerase chain reaction (RT-PCR) method. Treatment with Hb, NAME, or NAME + Hb elicited a significant improvement in mean BP and VR compared with the control (BSA) group (P < 0.05, analysis of variance and Neuman-Keuls tests). Tissue samples from 24-h CLP rats clearly exhibited iNOS gene expression; higher iNOS gene expression in the intestine compared with aorta suggests that the intestine may be a major source of the elevated NO level in this model. In conclusion, NO scavenging with Hb, alone, or in combination with NO synthesis inhibition, appears to be effective in modulating sepsis-mediated vascular hyporeactivity and may reduce complications associated with global NO synthesis inhibition.

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