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Research ArticleCardiovascular

Effect of Isoflurane on Myocardial Energetic and Oxidative Stress in Cardiac Muscle from Zucker Diabetic Fatty Rat

Xiaoxu Shen, Niraj Bhatt, Jianhong Xu, Tao Meng, Miguel A. Aon, Brian O’Rourke, Dan E. Berkowitz, Sonia Cortassa and Wei Dong Gao
Journal of Pharmacology and Experimental Therapeutics April 2014, 349 (1) 21-28; DOI: https://doi.org/10.1124/jpet.113.211144
Xiaoxu Shen
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Niraj Bhatt
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Jianhong Xu
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Tao Meng
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Miguel A. Aon
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Brian O’Rourke
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Dan E. Berkowitz
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Sonia Cortassa
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Wei Dong Gao
Cardiology Department, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China (X.S.); Division of Cardiology, Department of Medicine (N.B., M.A.A., B.O., S.C.), and Department of Anesthesiology and Critical Care Medicine (T.M., D.E.B., W.D.G.), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Anesthesiology, 1st Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China (J.X.)
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Abstract

The effect of inhalational anesthetics on myocardial contraction and energetics in type 2 diabetes mellitus is unknown. We investigated the effect of isoflurane (ISO) on force and intracellular Ca2+ transient (iCa), myocardial oxygen consumption (MVo2), and energetics/redox behavior in trabecular muscles from Zucker diabetic fatty (ZDF) rats. At baseline, force and corresponding iCa were lower in ZDF trabeculae than in controls. ISO decreased force in both groups in a dose-dependent manner. ISO did not affect iCa amplitude in controls, but ISO > 1.5% significantly reduced iCa amplitude in ZDF trabeculae. ISO-induced force depression fully recovered as a result of increased iCa when external Ca2+ was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca2+. In controls, force, iCa, and MVo2 increased when stimulation frequency was increased from 0.5 to 1.5 Hz. ZDF muscles, however, exhibited blunted responses in force and iCa and decreased MVo2. Oxidative stress levels were unchanged in control muscles but increased significantly in ZDF muscles after exposure to ISO. Finally, the depressive effect of ISO was prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) in ZDF muscles. These findings suggest that ISO dose-dependently attenuates force in control and ZDF muscles with differential effect on iCa. The mechanism of force depression by ISO in controls is mainly decreased myofilament Ca2+ sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development.

Footnotes

    • Received November 7, 2013.
    • Accepted January 14, 2014.
  • This work was supported in part by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant R21-HL106054] (to S.C.); and the American Heart Association [Grant 13GRNT16920028] (to W.D.G.).

  • dx.doi.org/10.1124/jpet.113.211144.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 349 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 349, Issue 1
1 Apr 2014
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Research ArticleCardiovascular

Isoflurane and Oxidative Stress in Diabetic Myocardium

Xiaoxu Shen, Niraj Bhatt, Jianhong Xu, Tao Meng, Miguel A. Aon, Brian O’Rourke, Dan E. Berkowitz, Sonia Cortassa and Wei Dong Gao
Journal of Pharmacology and Experimental Therapeutics April 1, 2014, 349 (1) 21-28; DOI: https://doi.org/10.1124/jpet.113.211144

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Research ArticleCardiovascular

Isoflurane and Oxidative Stress in Diabetic Myocardium

Xiaoxu Shen, Niraj Bhatt, Jianhong Xu, Tao Meng, Miguel A. Aon, Brian O’Rourke, Dan E. Berkowitz, Sonia Cortassa and Wei Dong Gao
Journal of Pharmacology and Experimental Therapeutics April 1, 2014, 349 (1) 21-28; DOI: https://doi.org/10.1124/jpet.113.211144
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