IngentaConnect The NO donor SIN-1 improves intestinalarterial Pco2 gap in experi...

Abstract:

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 μPo₂ 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.

Keywords: Drug effects; microcirculation; molsidomine analogs and derivatives; oxygen consumption; regional blood flow; septic shock; vasodilator agents

Document Type: Research article

DOI: 10.1111/j.1399-6576.2007.01334.x

Affiliations: 1: Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 2: Department of Anesthesia and Intensive Care, University Hospital, University of Basel, Basel, Switzerland

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

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