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Mitochondrial dysfunction in myocardium obtained from clinically normal dogs, clinically normal anesthetized dogs, and dogs with dilated cardiomyopathy

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  • 1 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • | 2 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • | 3 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • | 4 Department of Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • | 5 Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
  • | 6 Department of Mari Lowe Center for Comparative Oncology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.

Abstract

Objective—To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy.

Sample—Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy).

Procedures—Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs.

Results—Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy.

Conclusions and Clinical Relevance—Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Abstract

Objective—To compare mitochondrial complex I and complex IV activity in myocardial mitochondria of clinically normal dogs, clinically normal dogs exposed to inhalation anesthesia, and dogs affected with dilated cardiomyopathy.

Sample—Myocardial samples obtained from 21 euthanized dogs (6 clinically normal [control] dogs, 5 clinically normal dogs subjected to inhalation anesthesia with isoflurane prior to euthanasia, 5 dogs with juvenile-onset dilated cardiomyopathy, and 5 dogs with adult-onset dilated cardiomyopathy).

Procedures—Activity of mitochondrial complex I and complex IV was assayed spectrophotometrically in isolated mitochondria from left ventricular tissue obtained from the 4 groups of dogs.

Results—Activity of complex I and complex IV was significantly decreased in anesthetized dogs, compared with activities in the control dogs and dogs with juvenile-onset or adult-onset dilated cardiomyopathy.

Conclusions and Clinical Relevance—Inhalation anesthesia disrupted the electron transport chain in the dogs, which potentially led to an outburst of reactive oxygen species that caused mitochondrial dysfunction. Inhalation anesthesia depressed mitochondrial function in dogs, similar to results reported in other species. This effect is important to consider when anesthetizing animals with myocardial disease and suggested that antioxidant treatments may be beneficial in some animals. Additionally, this effect should be considered when designing studies in which mitochondrial enzyme activity will be measured. Additional studies that include a larger number of animals are warranted.

Contributor Notes

Dr. Rosato's present address is Atlantic Coast Veterinary Specialists, 3250 Veterans Hwy, Bohemia, NY 11716.

Supported by the National Institutes of Health/Merck-Merial Veterinary Scholars Program at the University of Pennsylvania School of Veterinary Medicine.

The authors thank Dr. Satish Srinivasan for technical assistance; Drs. Hansell Stedman, Paula Henthorn, and Petra Werner for provision of the samples; and Drs. Caryn Reynolds and Gretchen Singletary for assistance with the samples.

Address correspondence to Dr. Sleeper (sleeper@vet.upenn.edu).