Preservation of mitochondrial function with cardiopulmonary resuscitation in prolonged cardiac arrest in rats

Yeh, Steve T.; Lee, Hsin-Ling; Aune, Sverre E.; Chen, Chwen-Lih; Chen, Yeong-Renn; Angelos, Mark G.

doi:10.1016/j.yjmcc.2009.09.003

« Previous Next »Journal of Molecular and Cellular Cardiology
Volume 47, Issue 6 , Pages 789-797, December 2009

Preservation of mitochondrial function with cardiopulmonary resuscitation in prolonged cardiac arrest in rats

Steve T. Yeh
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
- Department of Emergency Medicine, The Ohio State University, Columbus, OH 43210, USA
- Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA
Hsin-Ling Lee
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Sverre E. Aune
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
- Department of Emergency Medicine, The Ohio State University, Columbus, OH 43210, USA
- Biophysics Graduate Program, The Ohio State University, Columbus, OH 43210, USA
Chwen-Lih Chen
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
Yeong-Renn Chen
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
- Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
- Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA
- Corresponding authors. M.G. Angelos is to be contacted at Department of Emergency Medicine, The Ohio State University, 4510 Cramblett Hall, 456 West 10th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 293 7536; fax: +1 614 293 3124. Y.-R. Chen, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, 607 DHLRI, 473 West 12th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 688 4054; fax: +1 614 292 8778.
Mark G. Angelos
- Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA
- Department of Emergency Medicine, The Ohio State University, Columbus, OH 43210, USA
- Corresponding authors. M.G. Angelos is to be contacted at Department of Emergency Medicine, The Ohio State University, 4510 Cramblett Hall, 456 West 10th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 293 7536; fax: +1 614 293 3124. Y.-R. Chen, Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, 607 DHLRI, 473 West 12th Avenue, Columbus, OH 43210, USA. Tel.: +1 614 688 4054; fax: +1 614 292 8778.

Received 6 May 2009; received in revised form 10 August 2009; accepted 4 September 2009. published online 14 September 2009.

Abstract

During cardiac arrest (CA), myocardial perfusion is solely dependent on cardiopulmonary resuscitation (CPR) although closed-chest compressions only provide about 10–20% of normal myocardial perfusion. The study was conducted in a whole animal CPR model to determine whether CPR-generated oxygen delivery preserves or worsens mitochondrial function. Male Sprague-Dawley rats (400–450 g) were randomly divided into four groups: (1) BL (instrumentation only, no cardiac arrest), (2) CA₁₅ (15 min cardiac arrest without CPR), (3) CA₂₅ (25 min cardiac arrest without CPR) and (4) CPR (15 min cardiac arrest, followed by 10 min CPR). The differences between groups were evaluated by measuring mitochondrial respiration, electron transport chain (ETC) complex activities and mitochondrial ultrastructure by transmission electron microscopy (TEM). The CA₂₅ group had the greatest impairment of mitochondrial respiration and ETC complex activities (I–III). In contrast, the CPR group was not different from the CA₁₅ group regarding all measures of mitochondrial function. Complex I was more susceptible to ischemic injury than the other complexes and was the major determinant of mitochondrial dysfunction. Observations of mitochondrial ultrastructure by TEM were compatible with the biochemical results. The findings suggest that, despite low blood flow and oxygen delivery, CPR is able to preserve heart mitochondrial function and viability during ongoing global ischemia. Preservation of complex I activity and mitochondrial function during cardiac arrest may be an important mechanism underlying the beneficial effects of CPR which have been shown in clinical studies.

Keywords: Mitochondria, Cardiopulmonary resuscitation, Cardiac arrest, Mitochondrial ultrastructure, Rat, Electron transport chain complexes, Complex I