Alterations of cross-bridge kinetics in human atrial and ventricular myocardium

Condensed abstract: We analyzed actomyosin cross-bridge kinetics in human a trial and ventricular muscle strip preparations by using sinusoidal length changes from 0.1 to 60 Hz. The minimum stiffness frequency was higher in at rial than in ventricular human myocardium and lower in failing than in non- failing left ventricular human myocardium. P-Adrenergic stimulation increas ed the minimum stiffness frequency by 18+/-3% (p<0.05). Cross-bridge kineti cs are temperature-dependent, with a Q(10) of at least 2.7. Background: Dyn amic stiffness measurements have revealed acute and chronic alterations of actomyosin cross-bridge kinetics in cardiac muscles of a variety of differe nt animal species. We studied dynamic stiffness in right atrial and left ve ntricular preparations of non-failing and failing human hearts and tested t he influence of the temperature and P-adrenergic stimulation on cross-bridg e kinetics. Methods and Results: Muscle strips were prepared from right atr ia and left ventricles from human non-failing and failing hearts. After wit hdrawal of calcium, steady contracture tension was induced by the addition of 1.5 mM barium chloride. Sinusoidal length oscillations of 1% muscle leng th were applied, with a frequency spectrum of between 0.1 and 60 Hz. Dynami c stiffness was calculated from the length change and the corresponding for ce response amplitude. The specific minimum stiffness frequency, which indi cates the interaction between cross-bridge recruitment and cross-bridge cyc ling dynamics, was analyzed for each condition: (I) The minimum stiffness f requency was 0.78+/-0.04 Wt in left ventricular myocardium and 2.80+/-0.31 Hz in right atrial myocardium (p<0.01) at 27 degrees C. (2) The minimum sti ffness frequency was 41% higher in non-failing compared to failing left ven tricular human myocardium. (3) Over a wide range of experimental temperatur es, the minimum stiffness frequency changed, with a Q(10) of at least 2.7. (4) beta-Adrenergic stimulation significantly (p<0.05) increased the minimu m stiffness to 18+/-3% higher frequencies and significantly (p<0.05) lowere d contracture tension by 7+/-1%. Conclusions: The, contractility of human h eart muscle is not only regulated by excitation-contraction coupling but al so by modulation of intrinsic properties of the actomyosin system. Acute an d chronic alterations of cross-bridge kinetics have been demonstrated, whic h play a significant role in the physiology and pathophysiology of the huma n heart. (C) 1998 Elsevier Science B.V. All rights reserved.