Regional Nonuniformity of Contraction in the Left Ventricular Free-wall

Abstract

The function of the heart is characterized by nonuniform wall motions working coordinately to generate a smooth and effective pump action; however, the functional importance of these heterogeneous motions are largely unknown. To bridge the understanding of the basis for regional variations in contraction, we have analyzed left ventricular free-wall motion using echocardiography and sonomicrometry and quantified the expression of protein levels and post-translational modifications using gel electrophoresis. Porcine myocardium was used for investigation and a stress test, i.e. dobutamine infusion, was performed to amplify transmural contractile gradients during beta-adrenergic stimulation. Here we report greater segmental shortening, strain and strain rate in the endocardium compared to the epicardium in both the longitudinal and circumferential directions (p<0.05), but not in the radial dimension, at baseline and during dobutamine infusion. The gradient of strain and shortening mirrors the expression of the myosin heavy chain isoforms, alpha- and beta-MyHC, across the wall, i.e., there is more alpha-MyHC in the epicardium. We propose that differences in expression of specific protein isoforms in healthy, control myocardium is directly related to the shorter period of stretch in the epicardium during the heart cycle, or stretch activation, and that differences in myosin heavy chain isoform content is a direct determinant of the strain differential. This work supported by NIH RO1-HL61635 (RLM) and T32-HL07936 (HSN).