Acto-myosin crossbridge kinetics in humans with coronary artery disease: Influence of sex and diabetes mellitus

Risk of heart failure (HF) is influenced by sex and diabetes mellitus (DM). To better understand these interactions, sub-epicardial myocardium from 26 patients with coronary artery disease (CAD) undergoing coronary bypass surgery was examined in vitro using sinusoidal length perturbation analysis at varying [Ca2+] to determine the viscoelastic properties of myofilaments related to acto-myosin crossbridge kinetics. Half of the patients had CAD only (four female, F-CAD; nine male, M-CAD), while the other half had both CAD and Type 2 DM (six F-DM; seven M-DM). At maximal and sub-maximal myofilament Ca2+ activation there was a significant effect of sex and disease on frequency of maximum oscillatory work output during sinusoidal perturbation (P < 0.05). Myofilaments from F-CAD produced oscillatory work at significantly higher frequencies compared with M-CAD, while myofilaments from F-DM and M-DM produced work at similar frequencies. Correspondingly, minimum viscoelastic stiffness at maximum Ca2+ activation occurred at significantly higher frequencies in F-CAD (5.0 +/- 0.3 Hz) than M-CAD (3.3 +/- 0.3 Hz), but at similar frequencies in F-DM (3.7 +/- 0.3 Hz) and M-DM (4.3 +/- 0.2 Hz). Thus, sex influences acto-myosin crossbridge kinetics in myofilaments isolated from CAD patients. These sex-related differences were absent in DM, suggesting that differences in the properties of cardiac muscle contribute to reported sex differences in the incidence and mortality of HF in DM. (c) 2005 Elsevier Ltd. All rights reserved.