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Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury

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Abstract

Each year, tens of thousands of children undergo cardiopulmonary bypass (CPB) to correct congenital heart defects. Although necessary for surgery, CPB involves stopping the heart and exposing it to ischemic conditions. On reoxygenation, the heart can experience effects similar to that of acute myocardial infarction. Although much is known about adult injury, little is known about the effects of global ischemia on newborn ventricles. We studied newborn (2 to 4 days old) and adult (>8 weeks old) rabbit hearts subjected to ischemia–reperfusion (30 min of ischemia and 60 min of reperfusion). Our data demonstrated chamber- and age-specific changes in oxidative stress. During ischemia, hydrogen peroxide (H2O2) increased in both right-ventricular (RV) and left-ventricular (LV) myocytes of the newborn, although only the RV change was significant. In contrast, there was no significant increase in H2O2 in either RV or LV myocytes of adults. There was a fivefold increase in H2O2 formation in newborn RV myocytes compared with adults (P = 0.006). In whole-heart tissue, superoxide dismutase activity increased from sham versus ischemia in the left ventricle of both adult and newborn hearts, but it was increased only in the right ventricle of the newborn heart. Catalase activity was significantly increased after ischemia in both adult ventricles, whereas no increase was seen in newborn compared with sham hearts. In addition, catalase levels in newborns were significantly lower, indicating less scavenging potential. Nanoparticle-encapsulated ebselen, given as an intracardiac injection into the right or left ventricle of newborn hearts, significantly increased functional recovery of developed pressure only in the right ventricle, indicating the potential for localized antioxidant therapy during and after pediatric surgical procedures.

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Acknowledgments

This work was supported in part by an Emory-Children’s Center for Cardiovascular Biology Pilot Grant from Children’s Healthcare of Atlanta (M. E. D., G. D.) as well as Grant Nos. HL094527 and HL090601 to M. E. D. The authors thank Pao Lin Che for help in nanoparticle synthesis.

Conflict of interest

M. E. Davis, as well as Emory University, are entitled to equity and royalties derived from Ketal Biomedical, Incorporated, which is developing products related to the nanoparticle technology described in this article. This study could affect their personal financial status. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies.

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Authors and Affiliations

  1. Wallace H. Coulter Department of Biomedical Engineering at Emory University, Georgia Institute of Technology, Atlanta, GA, 30322, USA

    E. Bernadette Cabigas, Karl D. Pendergrass & Michael E. Davis

  2. Division of Cardiology, Emory University School of Medicine, Atlanta, GA, 30322, USA

    E. Bernadette Cabigas, Karl D. Pendergrass & Michael E. Davis

  3. Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA

    Guoliang Ding, Tao Chen, Talib B. Saafir & Mary B. Wagner

  4. Emory-Children’s Center for Cardiovascular Biology, Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA

    Guoliang Ding, Tao Chen, Talib B. Saafir, Mary B. Wagner & Michael E. Davis

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  1. E. Bernadette Cabigas
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Correspondence to Michael E. Davis.

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Cabigas, E.B., Ding, G., Chen, T. et al. Age- and Chamber-Specific Differences in Oxidative Stress After Ischemic Injury. Pediatr Cardiol 33, 322–331 (2012). https://doi.org/10.1007/s00246-011-0137-z

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