Effects of reactive oxygen species on myofilament function in a rabbit coronary artery ligation model of heart failure

This study aimed to determine structural alterations occurring in cardiac myofilaments after exogenous application of oxidants and the effects of oxidants on contractile protein function in a rabbit coronary artery ligation model of heart failure. Myocardial "stiffness" was higher in the ligated animals (Lig) than sham-operated controls (Sh, 4.9+/-1.5 versus 1.6+/-0.8 mN.mm-1). Superoxide anion (O2-) exposure decreased active stiffness in both groups, whereas hypochlorous acid (HOCl) had no effect in Lig but increased stiffness in Sh. Resting stiffness was higher in Lig than Sh (0.6+/-0.2 versus 0.2+/-0.1 mN.mm-1), remaining unchanged after O2- exposure but increasing after HOCl in both groups. The frequency at minimum stiffness was lower in Lig than Sh (0.9+/-0.2 versus 1. 7+/-0.6 Hz) and was reduced in both groups after oxidant exposure. Myofilament calcium sensitivity (pCa50) was not altered by O2- in Sh but increased in Lig (pCa50 increased from 5.41+/-0.05 to 5.56+/-0. 06). Protease contamination in the xanthine oxidase used to generate O2- did not affect myofilament ultrastructure at the concentrations used here. These data demonstrate that contractile proteins from "failed" myocardium have a similar response to exogenously applied oxidants as controls and that application of protease-contaminated xanthine oxidase system does not degrade the contractile protein structure