The NO donor SIN-1 improves intestinal-arterial Pco2 gap in experimental endotoxemia: An animal study

M. Siegemund, J. Van Bommel, M. Sinaasappel, L. A. Schwarte, W. Studer, T. Girard, K. Vollebregt, C. Ince

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Background: Dysfunction of the microcirculation is a prominent feature of sepsis and endotoxemia. Recently, it has been shown that microcirculatory alterations are completely reversed by local or systemic application of vasodilators in severely septic patients. Therefore, we investigated the influence of vasodilator therapy on microcirculatory dysfunction of the ileum during endotoxic shock in a prospective, controlled animal study. Methods: After baseline measurements, shock was induced in 12 domestic pigs by lipopolysaccharide via the mesenteric vein until the mean arterial pressure fell below 60 mmHg. After 30 min in shock, six animals were resuscitated with either fluid alone (control) or fluid and 2 μg/kg/min of the vasodilator 3-morpholino-sydnonimine (SIN-1). The systemic and regional hemodynamics and oxygenation parameters, tonometric ileal Pco2 and microvascular oxygen pressures (μPo2) (by oxygen-dependent Pd-porphyrin phosphorescence) were measured simultaneously. Results: The ileal-arterial Pco2 gap increased during shock and the ileal mucosal and serosal μPo2 decreased concurrently. SIN-1 in addition to fluid resuscitation significantly improved the ileal-arterial Pco2 gap, whereas fluid alone failed to decrease the Pco2 gap. The SIN-1-induced improvement in the Pco2 gap was accompanied by an increase in serosal μPo2 above shock levels. Mucosal μPo 2 was resuscitated to baseline levels in both groups. Conclusion: The application of the vasodilator SIN-1 in addition to fluid resuscitation improves the ileal-arterial Pco2 gap and mucosal μPo2, together with a moderate increase in serosal μPo2, after endotoxic shock. This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall.

Original languageEnglish
Pages (from-to)693-700
Number of pages8
JournalActa anaesthesiologica Scandinavica
Issue number6
Publication statusPublished - Jul 2007


  • Drug effects
  • Microcirculation
  • Molsidomine analogs and derivatives
  • Oxygen consumption
  • Regional blood flow
  • Septic shock
  • Vasodilator agents

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