• Clemens Bauer, Wolfgang Kuntz, Frauke Ohnsmann, Harald Gasser, Carina Weber, Heinz Redl, and Ingo Marzi.
• Departments of Trauma Surgery and Anesthesiology, University of Saarland, Homburg/Saar, Germany.
• Shock. 2004 Feb 1; 21 (2): 165-9.

AbstractHepatic microcirculatory disorders such as narrowing of sinusoids after hemorrhagic shock play a major role in the pathogenesis of organ failure. It is known that the balance of vasoactive mediators such as endothelin and nitric oxide (NO) regulate microvascular perfusion, including the diameter of hepatic sinusoids. The present study was designed to evaluate the role of exogenous substitution of NO by S-nitroso-albumin (S-NO-HSA) in the prevention of pathophysiological alterations of hepatic microcirculation. Anesthetized Sprague-Dawley rats were instrumented for invasive hemodynamic monitoring. Hemorrhagic shock was induced by bleeding to a mean arterial pressure (MAP) of 40 mmHg and was maintained for 60 min. Thereafter, the animals were resuscitated with shed blood and Ringer's solution. During the first hour of resuscitation, S-NO-HSA or pure HSA was infused continuously (10 micromol/kg/h) and hepatic microcirculation was detected by intravital epifluorescence microscopy either 5 or 24 h after the insult. Results were compared with a sham-treated group (n = 6-8 per group). Shock-induced microcirculatory narrowing of sinusoids was significantly reduced in the S-NO-HSA group compared with the HSA group both at 5 and 24 h (HSA: 9.3 +/- 0.2 microm; S-NO-HSA: 12.1 +/- 0.2 microm, P < 0.05). Sinusoidal perfusion was significantly higher in the S-NO-HSA group than in the HSA group (HSA: 50,934 +/- 1,382 microm3/s; S-NO-HSA: 78,120 +/- 2,348 microm3/s, P < 0.05). Reversible leukocyte adhesion to sinusoidal endothelium, an indicator of the inflammatory response, was significantly reduced in the S-NO-HAS-treated group. The findings of this study in a rat model of hemorrhagic shock suggest that NO substitution by S-NO-HSA during resuscitation attenuates both early and late hepatic microcirculatory disturbances as well as the increase in leukocyte adherence.

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