Early versus delayed cyclosporine treatment in cardiac recovery and intestinal injury during resuscitation of asphyxiated newborn piglets

Abstract

We previously demonstrated that treating asphyxiated newborn piglets with cyclosporine immediately following resuscitation can improve cardiac and intestinal recovery. However, immediate treatment may not be feasible for a large portion of neonates delivered in peripheral or rural hospitals. Therefore, our objective was to determine if delayed cyclosporine treatment remained effective in treating neonatal asphyxia. We hypothesized that early and delayed cyclosporine treatment would improve cardiac and intestinal recovery during resuscitation of asphyxiated newborn piglets. Thirty piglets (1-4 days old) were instrumented for continuous monitoring of cardiac output and mesenteric hemodynamics. After stabilization, normocapnic alveolar hypoxia (10-15 % oxygen) was instituted for 2 h followed by reoxygenation with 100 % oxygen for 0.5 h, then 21 % for 5.5 h. Piglets were block-randomized to receive either intravenous bolus of cyclosporine A (10 mg/kg) or normal saline (control) at 5 or 120 min of reoxygenation (early or delayed, respectively; n = 8/group). Myocardial and intestinal lactate concentrations as well as histological examinations were determined. Hypoxic piglets had cardiogenic shock (cardiac output 52 ± 1 % of baseline, mean arterial pressure 32 ± 1 mmHg) and acidosis (pH 6.98 ± 0.1). Although both cyclosporine treatments improved cardiac output (p < 0.05 vs. controls), only early cyclosporine treatment improved stroke volume and systemic oxygen delivery (p < 0.05 vs. controls). Left ventricle and intestinal lactate were lowered in both cyclosporine-treated groups (p < 0.05 vs. controls). Early, but not delayed, cyclosporine treatment also attenuated intestinal injury (p < 0.05 vs. controls). This study demonstrates that treating asphyxiated newborn piglets with cyclosporine within 2 h of resuscitation is effective with superior cardioprotection and intestinal injury attenuation with early treatment.