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Purpose Hypoxia and reoxygenation (H-R) contributes to multi-organ failure in neonates, including cardiac and systemic complications. Use of vasopressin, an endogenous vasoconstrictive hormone commonly used to treat refractory hypotension in adults, in neonates with shock remains limited and not yet fully studied. We hypothesize that vasopressin will improve mean arterial pressure (MAP), without compromising cardiac, mesenteric, or carotid hemodynamics using a swine model of neonatal asphyxia. Methods Anesthetized piglets (1-4 days old, 1.4-2.5 kg, n = 33) were instrumented for continuous monitoring of cardiac index (CI), MAP, and regional arterial [common carotid (CA), superior mesenteric (SMA)] flow. The animals underwent hypoxia at 10-15% oxygen (2 h) followed by reoxygenation at 100% (0.5 h) and 21% (3.5 h) oxygen. Vasopressin infusion was initiated after 2 h reoxygenation at 0.005, 0.01, or 0.02 units/kg/h i.v. for 2 h (n = 7/group). H-R control (saline infusion) and sham-operated (non-asphyxiated) groups were also included. Intermittent blood gases and plasma lactate were determined as well as tissue lactate levels. Statistical significance was determined using ANOVA. Results All H-R piglets had hypotension (36-49% decrease in MAP) and decreased regional blood flows (CA -28 to -34%, SMA -12 to +32% of baseline) at 2 h reoxygenation. Vasopressin infusion dose-dependently increased MAP (14% at 0.02 units/kg/h, P < 0.05) without significant detrimental effects in CI, regional blood flows, and intestinal or cerebral tissue lactate levels. Conclusions Vasopressin treatment causes a dose-dependent baro-specific effect, while preserving cardiac function and cerebral and mesenteric hemodynamics in newborn piglets following H-R., Author(s): Douglas C. Cheung [sup.1], Richdeep S. Gill [sup.1] [sup.2], Jiang-Qin Liu [sup.1] [sup.3], Namdar Manouchehri [sup.1] [sup.2], Consolato Sergi [sup.1] [sup.4], David Bigam [sup.1] [sup.2], Po-Yin Cheung [sup.1] [sup.3], [...]