Early Impairment of Cerebral Bioenergetics After Cardiopulmonary Bypass in Neonatal Swine

Autor: Aronowitz, Danielle I., Geoffrion, Tracy R., Piel, Sarah, Benson, Emilie J., Morton, Sarah R., Starr, Jonathan, Melchior, Richard W., Gaudio, Hunter A., Degani, Rinat E., Widmann, Nicholas J., Weeks, M. Katie, Ko, Tiffany S., Licht, Daniel J., Hefti, Marco, Gaynor, J. William, Kilbaugh, Todd J., Mavroudis, Constantine D.
Zdroj: World Journal for Pediatric and Congenital Heart Surgery; 20240101, Issue: Preprints
Abstrakt: Objectives:We previously demonstrated cerebral mitochondrial dysfunction in neonatal swine immediately following a period of full-flow cardiopulmonary bypass (CPB). The extent to which this dysfunction persists in the postoperative period and its correlation with other markers of cerebral bioenergetic failure and injury is unknown. We utilized a neonatal swine model to investigate the early evolution of mitochondrial function and cerebral bioenergetic failure after CPB. Methods:Twenty piglets (mean weight 4.4 ± 0.5 kg) underwent 3 h of CPB at 34 °C via cervical cannulation and were followed for 8, 12, 18, or 24 h (n = 5 per group). Markers of brain tissue damage (glycerol) and bioenergetic dysfunction (lactate to pyruvate ratio) were continuously measured in cerebral microdialysate samples. Control animals (n = 3, mean weight 4.1 ± 1.2 kg) did not undergo cannulation or CPB. Brain tissue was extracted immediately after euthanasia to obtain ex-vivo cortical mitochondrial respiration and frequency of cortical microglial nodules (indicative of cerebral microinfarctions) via neuropathology. Results:Both the lactate to pyruvate ratio (P< .0001) and glycerol levels (P= .01) increased in cerebral microdialysate within 8 h after CPB. At 24 h post-CPB, cortical mitochondrial respiration was significantly decreased compared with controls (P= .046). The presence of microglial nodules increased throughout the study period (24 h) (P= .01, R2 = 0.9). Conclusion:CPB results in impaired cerebral bioenergetics that persist for at least 24 h. During this period of bioenergetic impairment, there may be increased susceptibility to secondary injury related to alterations in metabolic delivery or demand, such as hypoglycemia, seizures, and decreased cerebral blood flow.
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