ENDOTOXIC-SHOCK AFTER LONG-TERM RESUSCITATION OF HEMORRHAGE REPERFUSION INJURY DECREASED SPLANCHNIC BLOOD-FLOW AND EICOSANOID RELEASE/

Objective The authors examine the hypothesis that hemorrhage/reperfusi on injury predisposes the splanchnic bed to decreased prostacyclin (PG I(2)) release and blood flow after subsequent endotoxin challenge. Sum mary Background Data Prostacyclin is a potent vasodilator that has bee n demonstrated to be an important regulator of splanchnic blood flow. Previous studies have demonstrated that during resuscitation from seve re hemorrhage, there is a marked reduction in intestinal PGI(2) levels , which is associated with reduced splanchnic perfusion. Methods Anest hetized Sprague-Dawley rats underwent hemorrhage to a mean arterial pr essure of 30 mmHg for 30 minutes followed by the reinfusion of shed bl ood. Then the animals were maintained on total parenteral nutrition (T PN) for 10 days, after which time they received 20 mg/kg Escherichia c oli endotoxin intraperitoneally. Aortic and superior mesenteric artery (SMA) blood flow was monitored with a Doppler flow probe. The splanch nic bed was excised and perfused in vitro for measurement of venous ef fluent eicosanoid concentrations. Controls consisted of animals that r eceived TPN and endotoxin but did not undergo hemorrhage and resuscita tion (sham). Results Total parenteral nutrition support of sham animal s followed by endotoxin challenge did not alter splanchnic eicosanoid release or blood flow. Hemorrhage/reperfusion animals supported by lon g-term TPN and challenged with endotoxin demonstrated a threefold decr ease in splanchnic prostacyclin metabolite (6-keto-PGF(1a)) release an d a 59% decrease in SMA blood flow. Conclusions Hemorrhage/reperfusion injury predisposes the splanchnic bed from rats sustained with long-t erm TPN to decreased release of PGI(2) and SMA blood flow when challen ged with eodotoxin as a second injury.