Journal
CRITICAL CARE MEDICINE
Volume 41, Issue 4, Pages 1069-1074Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e3182746704
Keywords
asphyxia; cyclosporine A; mitochondria; myocardium; newborn; piglets
Categories
Funding
- Canadian Institutes of Health Research, Ottawa, Canada [MOP53116]
- Royal College of Physicians and Surgeons of Canada, Ottawa, Canada
- Alberta Innovates Health Solutions (AIHS), Alberta, Canada
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Objectives: Cardiovascular dysfunction occurs in the majority of asphyxiated neonates and has been suggested to be a major cause of neonatal morbidity and mortality. We previously demonstrated that cyclosporine A treatment during resuscitation can significantly improve cardiovascular performance in asphyxiated newborn piglets. However, the mechanisms through which cyclosporine elicits its protective effect in neonates have not yet been fully characterized. We hypothesized that cyclosporine A treatment would attenuate myocardial and cardiac mitochondrial injury during the resuscitation of asphyxiated newborn piglets. Design: After acute instrumentation, piglets received normocapnic alveolar hypoxia (10% to 15% oxygen) for 2 hours followed by reoxygenation with 100% oxygen (0.5 hr) and then 21% oxygen (3.5 hr). At 4 hours of reoxygenation, plasma troponin level, left ventricle myocardial levels of lipid hydroperoxides, cytochrome-c, and mitochondrial aconitase activity were determined. Setting: Neonatal asphyxia and reoxygenation. Subjects: Twenty-four newborn (1-4 days old) piglets. Interventions: Piglets were randomized to receive an IV bolus of cyclosporine A (10 mg/kg) or normal saline (placebo, control) at 5 minutes of reoxygenation (n = 8/group). Sham-operated piglets (n = 8) underwent no asphyxia-reoxygenation. Measurements and Main Results: Asphyxiated piglets treated with cyclosporine had lower plasma troponin and myocardial lipid hydroperoxides levels (vs. controls, both p < 0.05, analysis of variance). Cyclosporine treatment also improved mitochondrial aconitase activity and attenuated the rise in cytosol cytochrome-c level (vs. controls, all p < 0.05). The improved mitochondrial function significantly correlated with cardiac output (p < 0.05, Spearman rank-correlation test). Conclusions: We demonstrate that the postresuscitation administration of cyclosporine attenuates myocardial and cardiac mitochondrial injury in asphyxiated newborn piglets following resuscitation. (Crit Care Med 2013; 41: 1069-1074)
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