Protection from systemic pyruvate at resuscitation in newborn lambs with asphyxial cardiac arrest

Vasantha H.S. Kumar, Sylvia Gugino, Lori Nielsen, Praveen Chandrasekharan, Carmon Koenigsknecht, Justin Helman, Satyan Lakshminrusimha

Research output: Contribution to journalArticle

Abstract

Background: Infants with hypoxic-ischemic injury often require cardiopulmonary resuscitation. Mitochondrial failure to generate adenosine triphosphate (ATP) during hypoxic-ischemic reperfusion injury contributes to cellular damage. Current postnatal strategies to improve outcome in hypoxic-ischemic injury need sophisticated equipment to perform servo-controlled cooling. Administration of intravenous pyruvate, an antioxidant with favorable effects on mitochondrial bioenergetics, is a simple intervention that can have a global impact. We hypothesize that the administration of pyruvate following the return of spontaneous circulation (ROSC) would improve cardiac function, systemic hemodynamics, and oxygen utilization in the brain in newborn lambs with cardiac arrest (CA). Methods: Term lambs were instrumented, delivered by C-section and asphyxia induced by umbilical cord occlusion along with clamping of the endotracheal tube until asystole; Lambs resuscitated following 5 min of CA; upon ROSC, lambs were randomized to receive pyruvate or saline infusion over 90 min and ventilated for 150 min postinfusion. Pulmonary and systemic hemodynamics and arterial gases monitored. We measured plasma pyruvate, tissue lactate, and ATP levels (heart and brain) in both groups. Results: Time to ROSC was not different between the two groups. Systolic and diastolic blood pressures, stroke volume, arterial oxygen content, and cerebral oxygen delivery were similar between the two groups. The cerebral metabolic rate of oxygen was higher following pyruvate infusion; higher oxygen consumption in the brain was associated with lower plasma levels but higher brain ATP levels compared to the saline group. Conclusions: Pyruvate promotes energy generation accompanied by efficient oxygen utilization in the brain and may facilitate additional neuroprotection in the presence of hypoxic-ischemic injury.

Original languageEnglish (US)
Article numbere14472
JournalPhysiological Reports
Volume8
Issue number12
DOIs
StatePublished - Jun 1 2020
Externally publishedYes

Keywords

  • ATP
  • cardiac arrest
  • CMRO
  • hypoxic-ischemic injury
  • newborns
  • pyruvate
  • resuscitation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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    Kumar, V. H. S., Gugino, S., Nielsen, L., Chandrasekharan, P., Koenigsknecht, C., Helman, J., & Lakshminrusimha, S. (2020). Protection from systemic pyruvate at resuscitation in newborn lambs with asphyxial cardiac arrest. Physiological Reports, 8(12), [e14472]. https://doi.org/10.14814/phy2.14472