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, Wei Dong Gao

Research output: Contribution to journalArticle

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 Ca 2+. 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.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume349
Issue number4
DOIs
StatePublished - Apr 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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