title: Effect of isoflurane on myocardial energetic and oxidative stress in cardiac muscle from Zucker diabetic fatty rat.
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 Ca(2+) transient (iCa), myocardial oxygen consumption (MVo(2)), 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 Ca(2+) was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca(2+). In controls, force, iCa, and MVo(2) 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 MVo(2). 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 Ca(2+) sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development.
authors.affiliation: 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.).
authors.forename: Xiaoxu
authors.initials: X
authors.lastname: Shen
authors.forename: Niraj
authors.initials: N
authors.lastname: Bhatt
authors.forename: Jianhong
authors.initials: J
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Meng
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Aon
authors.forename: Brian
authors.initials: B
authors.lastname: O'Rourke
authors.forename: Dan E
authors.initials: DE
authors.lastname: Berkowitz
authors.forename: Sonia
authors.initials: S
authors.lastname: Cortassa
authors.forename: Wei Dong
authors.initials: WD
authors.lastname: Gao
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D007530:Isoflurane / Q000008:administration & dosage / Q000009:adverse effects*; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane; D002118:Calcium