Preservation of Mitochondrial Structure and Function After Cardioplegic Arrest in the Neonate Using a Selective Mitochondrial KATP Channel Opener

Lixing Wang, Caroline Kinnear, James M Hammel, Wei Zhu, Zhongdong Hua, Wenyu Mi, Christopher A. Caldarone

Research output: Contribution to journalArticle

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Abstract

Background: Mitochondrial dysfunction may contribute to early postoperative neonatal heart dysfunction. Diazoxide, a mitochondrial-selective adenosine triphosphate-sensitive potassium-channel opener, is associated with mitochondrial preservation after cardioplegic arrest. We evaluated the mitochondrial-protective effect of diazoxide in terms of mitochondrial structure and function after neonatal cardioplegic arrest. Methods: Newborn piglets (age, approximately 14 days) underwent cardiopulmonary bypass and 60 minutes of cardioplegic arrest using cold crystalloid cardioplegic solution (CCP, n = 5) or cold crystalloid cardioplegic solution with diazoxide (CCP+D, n = 5). After 6 hours of recovery, myocardium was harvested. Control myocardium from piglets that did not undergo cardiopulmonary bypass (non-CPB, n = 5) was obtained. Results: Cardioplegic arrest was associated with translocation of Bax to the mitochondria, which was not prevented by diazoxide. Nevertheless, by electron microscopy, CCP-associated remodeling of mitochondrial structure was subjectively diminished in CCP+D hearts. In addition, CCP-associated mitochondrial permeabilization and cytochrome c release into the cytosol were prevented with CCP+D (p < 0.05). In vitro oxygen consumption of isolated mitochondria demonstrated deficient function of mitochondrial complex I in CCP, but it was preserved in the CCP+D myocardial mitochondria (p < 0.05). Complex II and IV activity was not different among groups. In parallel with impaired complex I function, the cardiac adenosine triphosphate content was diminished in CCP hearts, but well maintained in CCP+D hearts (p < 0.05). Conclusions: Although early apoptotic signaling events (Bax translocation) are not prevented by diazoxide, addition of the mitochondrial-selective adenosine triphosphate-sensitive potassium-channel opener to the cardioplegic solution is associated with protection of mitochondrial structural and functional integrity in a clinically relevant model of neonatal cardiac surgery. The mitochondrial-protective effects of diazoxide may contribute to improved postoperative myocardial function in the neonate.

Original languageEnglish (US)
Pages (from-to)1817-1823
Number of pages7
JournalAnnals of Thoracic Surgery
Volume81
Issue number5
DOIs
StatePublished - May 1 2006

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Diazoxide
Adenosine Triphosphate
Potassium Channels
Cardiopulmonary Bypass
Myocardium
Mitochondria
Cardioplegic Solutions
Heart Mitochondria
Cytochromes c
Oxygen Consumption
Cytosol
Thoracic Surgery
mitochondrial K(ATP) channel
Electron Microscopy

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Preservation of Mitochondrial Structure and Function After Cardioplegic Arrest in the Neonate Using a Selective Mitochondrial KATP Channel Opener. / Wang, Lixing; Kinnear, Caroline; Hammel, James M; Zhu, Wei; Hua, Zhongdong; Mi, Wenyu; Caldarone, Christopher A.

In: Annals of Thoracic Surgery, Vol. 81, No. 5, 01.05.2006, p. 1817-1823.

Research output: Contribution to journalArticle

Wang, Lixing ; Kinnear, Caroline ; Hammel, James M ; Zhu, Wei ; Hua, Zhongdong ; Mi, Wenyu ; Caldarone, Christopher A. / Preservation of Mitochondrial Structure and Function After Cardioplegic Arrest in the Neonate Using a Selective Mitochondrial KATP Channel Opener. In: Annals of Thoracic Surgery. 2006 ; Vol. 81, No. 5. pp. 1817-1823.
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AU - Kinnear, Caroline

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AU - Zhu, Wei

AU - Hua, Zhongdong

AU - Mi, Wenyu

AU - Caldarone, Christopher A.

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