Abstract
Introduction: Asphyxiated neonates commonly have multi-organ failure. Cyclosporine has recently been shown to improve systemic hemodynamics, however, its effects on the regional circulation have not yet been studied. We hypothesize that cyclosporine in asphyxiated newborn piglets will dose-dependently improve regional hemodynamics and oxygen metabolism.
Methods: Piglets (1-4 days-old) were acutely instrumented for continuous monitoring of common carotid (CA), superior mesenteric (SMA) and renal (RA) arterial flows. After stabilization, normocapnic alveolar hypoxia (10-15% oxygen) was instituted for 2h followed by reoxygenation with 100% oxygen for 0.5h, then 21% for 3.5h. Piglets were blockrandomized to receive one of three cyclosporine intravenous boluses (2.5, 10 or 25 mg/kg) or placebo (normal saline, control) after 5 minutes of 100% reoxygenation (n=8/group). Blood samples were collected for co-oximetry analysis and oxygen transport calculation. Statistical analysis was performed using ANOVA.
Results: All piglets had decreased regional blood flow (CA 52-64%, SMA 34-56%, RA 25-35% compared to respective baseline), hypotension (mean arterial pressure 30mmHg) and acidosis (pH 7.04) at 2h of hypoxia. Cyclosporine (2.5 and 10 mg/ kg) treatment at reoxygenation caused dose-related improvements in SMA flow and oxygen delivery. Cyclosporine (10 mg/kg) significantly increased RA flow and oxygen delivery (P< 0.05 vs. controls). While CA flows were not different among groups, cyclosporine (25 mg/kg) had significantly higher CA oxygen delivery than controls.
Conclusion: In newborn piglets following asphyxiareoxygenation, post-resuscitation administration of cyclosporine caused differential and dose-related improvements of regional perfusion.
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Gill, R., Manouchehri, N., Liu, JQ. et al. 333 Cyclosporine and Regional Hemodynamics of Newborn Piglets Following Asphyxia-Reoxygenation: A Dose-Response Study. Pediatr Res 68 (Suppl 1), 171 (2010). https://doi.org/10.1203/00006450-201011001-00333
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DOI: https://doi.org/10.1203/00006450-201011001-00333