PURPOSE: To compare the effects of first-line therapy with low-dose arginine vasopressin (AVP) or terlipressin (TP) on mesenteric blood flow, plasma AVP levels, organ function and mortality in ovine septic shock. METHODS: Twenty-four adult ewes were anesthetized and instrumented for chronic hemodynamic monitoring. A flow-probe was placed around the superior mesenteric artery, and feces were extracted from the cecum. Following baseline measurements, feces were injected into the peritoneal cavity. When mean arterial pressure (MAP) decreased to less than 60 mmHg, animals were randomly assigned to receive AVP (0.5 mU kg(-1) min(-1)), TP (1 microg kg(-1) h(-1)) or saline (n = 8 each). A norepinephrine infusion was titrated to maintain MAP at 70 +/- 5 mmHg in all groups. RESULTS: Cardiovascular pressures, cardiac output, mesenteric blood flow, and lung tissue concentrations of 3-nitrotyrosine and hemoxygenase-1 were similar among groups throughout the study period. TP infusion resulted in lower plasma AVP concentrations, reduced positive net fluid balance, increased central venous oxygen saturation and slightly prolonged survival compared to control and AVP-treated animals. However, TP treatment was associated with higher liver transaminases and lactate dehydrogenase versus control animals after 12 h. CONCLUSIONS: This study provides evidence that the effects of low-dose TP differ from those of AVP, not only as TP has a longer half life, but also because of different mechanisms of action. Although low-dose TP infusion may be superior to sole norepinephrine or AVP therapy in septic shock, the safety of this therapeutic approach should be determined in more detail.
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