RT Journal Article SR Electronic T1 Effect of Isoflurane on Myocardial Energetic and Oxidative Stress in Cardiac Muscle from Zucker Diabetic Fatty Rat JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 21 OP 28 DO 10.1124/jpet.113.211144 VO 349 IS 1 A1 Xiaoxu Shen A1 Niraj Bhatt A1 Jianhong Xu A1 Tao Meng A1 Miguel A. Aon A1 Brian O’Rourke A1 Dan E. Berkowitz A1 Sonia Cortassa A1 Wei Dong Gao YR 2014 UL http://jpet.aspetjournals.org/content/349/1/21.abstract AB 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.