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 21 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 dosedependent 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 21 was raised in controls. However, both force and iCa remained low in ZDF muscle at elevated external Ca 21 . 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 21 sensitivity, whereas in ZDF muscles the ISO-induced decrease in contraction is due to worsening oxidative stress, which inhibits iCa and force development.

Restoring redox balance enhances contractility in heart trabeculae from type 2 diabetic rats exposed to high glucose

“…GSH was determined with 50 M monochlorobimane (MCB), a membrane-permeant indicator of GSH (2). Trabeculae were loaded with 7 M CM-H 2-DCFDA and 2 M MitoSOX dissolved in 0.4% pluronic acid F-127, 0.1% DMSO, 5g/l cremophor, and 1 M N,N,N=,N= tetrakis (2-pyridylmethyl)ethylenediamine (48,52).…”

Impact of Volatile Anesthetics on Oxidative Stress and Inflammation

“…Among various comorbidities in diabetic patients, coronary heart diseases is linked with stroke and early death. Interestingly, isoflurane (up to 3%) was reported to decrease myocardial contraction and oxidative stress, the common symptoms of coronary heart diseases, in Zucker diabetic fatty rats [ 34 ]. When general inflammation was induced by Zymosan in mice, a subanesthetic dose of isoflurane (0.7%) increased the survival rate from 10% to 45% and reduced inflammation by upregulating antioxidant enzymes such as superoxide dismutase and catalase in blood and lung tissue.…”

Heart Failure after Cardiac Surgery: The Role of Halogenated Agents, Myocardial Conditioning and Oxidative Stress

“…Regarding the studies carried out to relate both drugs to ROS production, paradoxically. it has been observed that they may be involved in the beneficial effects of volatile anesthetics used in preconditioning [103,104].…”