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 m yofilaments after exogenous application of oxidants and the effects of oxid ants on contractile protein function in a rabbit coronary artery ligation m odel of heart failure. Myocardial "stiffness" was higher in the ligated ani mals (Lig) than sham-operated controls (Sh, 4.9+/-1.5 versus 1.6+/-0.8 mN.m m(-1)). Superoxide anion (O-2(-)) exposure decreased active stiffness in bo th groups, whereas hypochlorous acid (HOCl) had no effect in Lig but increa sed 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 OZ expo sure but in creasing 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 bot h groups after oxidant exposure. Myofilament calcium sensitivity (pCa(50)) was not altered by O-2(-) in Sh but increased in Lig (pCa(50) increased fro m 5.41+/-0.05 to 5.56+/-0.06). Protease contamination in the xanthine oxida se used to generate O-2(-) 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 ox idants as controls and that application of protease-contaminated xanthine o xidase system does not degrade the contractile protein structure.