The NO donor SIN-1 improves intestinal-arterial P(CO(2)) gap in experimental endotoxemia: an animal study.
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 microg/kg/min of the vasodilator 3-morpholino-sydnonimine (SIN-1). The systemic and regional hemodynamics and oxygenation parameters, tonometric ileal P(CO(2)) and microvascular oxygen pressures (muP(O(2))) (by oxygen-dependent Pd-porphyrin phosphorescence) were measured simultaneously.


RESULTS
The ileal-arterial P(CO(2)) gap increased during shock and the ileal mucosal and serosal muP(O(2)) decreased concurrently. SIN-1 in addition to fluid resuscitation significantly improved the ileal-arterial P(CO(2)), whereas fluid alone failed to decrease the P(CO(2)) gap. The SIN-1-induced improvement in the P(CO(2)) gap was accompanied by an increase in serosal muP(O(2)) above shock levels. Mucosal muP(O(2)) was resuscitated to baseline levels in both groups.


CONCLUSIONS
The application of the vasodilator SIN-1 in addition to fluid resuscitation improves the ileal-arterial P(CO(2)) gap and mucosal muP(O(2)), together with a moderate increase in serosal muP(O(2)), after endotoxic shock. This finding is consistent with the concept that vasodilators may correct pathologic flow distribution within the intestinal wall.
Siegemund
M
M
Department of Physiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Van Bommel
J
J
Sinaasappel
M
M
Schwarte
L A
LA
Studer
W
W
Girard
T
T
Vollebregt
K
K
Ince
C
C
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008833:Microcirculation; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012039:Regional Blood Flow; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D002245:Carbon Dioxide; C002385:linsidomine; D008981:Molsidomine; D010100:Oxygen