Differential Effects of Normoxic and Hyperoxic Reperfusion on Global Myocardial Ischemia-Reperfusion Injury

Yun Wen Peng, Azmath Mohammed, Kristopher B. Deatrick, Terry Major, Dorothy Cheng, Ian Charpie, John R. Charpie

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The objectives were to investigate if after hypoxia or ischemia, normoxic reperfusion is associated with less oxidant stress (OS), inflammation, and myocardial injury than hyperoxic reperfusion. In this study, cardiomyocytes (H9c2 cells) were cultured in hypoxia, followed by reoxygenation in normoxia or hyperoxia. Cardiomyocyte OS, inflammation, and apoptosis were measured. In parallel experiments, rabbits were cannulated for cardiopulmonary bypass (CPB). Following cardioplegic arrest and aortic cross-clamp removal, hearts were reperfused under normoxic or hyperoxic conditions. Left ventricular developed pressure and contractility (LV +dP/dt) were recorded, and blood samples and heart tissues were collected for measurement of OS, inflammation, and cardiac injury. Results showed that H9c2 cells exposed to hyperoxic reoxygenation showed significant increases in OS, inflammation, and apoptosis compared to normoxic reoxygenation. Following CPB and 2-hour hyperoxic reperfusion, LV +dP/dt and left ventricular developed pressure were significantly decreased compared with pre-CPB values (to 36 ± 21%, P = 0.002; and 53 ± 20%, P = 0.02, respectively), associated with significant increases in all plasma and tissue biomarkers for OS, inflammation, and myocardial injury. In contrast, LV +dP/dt was relatively well preserved under normoxic reperfusion conditions (to 70 ± 14% after 2-hour reperfusion), and was associated with an attenuated myocardial OS, inflammatory, apoptotic, and injury response compared to the hyperoxia group (eg, cTn-I: 5.9 ± 1.5 vs 20.2 ± 7.6 ng/mL, respectively, P < 0.0001). Overall, in both in vitro and in vivo experiments, normoxic reperfusion/reoxygenation was associated with less robust OS, inflammation, apoptosis, and myocardial injury compared with hyperoxic reperfusion/reoxygenation. These results suggest that hyperoxia should be avoided to minimize myocardial OS, inflammation, and ventricular dysfunction after CPB.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalSeminars in thoracic and cardiovascular surgery
Volume31
Issue number2
DOIs
StatePublished - Jun 1 2019

Bibliographical note

Funding Information:
Funding Source: This research was supported by the research grant from Caden's Full Throttle Event supporting the University of Michigan C.S. Mott Children's Hospital Congenital Heart Center.

Publisher Copyright:
© 2018 Elsevier Inc.

Keywords

  • Cardiopulmonary bypass
  • Ischemia
  • Myocardial injury
  • Normoxic/hyperoxic reperfusion

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