Human heart failure: determinants of ventricular dysfunction.
Thin muscle strips were obtained from non-failing (NF) and failing (dilated cardiomyopathy (DCM)) hearts, using a new harvesting and dissection technique. The strips were used to carry out a myothermal and mechanical analysis so that contractile and excitation coupling phenomena in the NF and failing (DCM-F) preparations can be compared. Peak isometric force and rate of relaxation in DCM-F were reduced 46% (p < 0.02) while time to peak tension was increased 14% (p < 0.03). Initial, tension dependent, tension independent and the rate of tension independent heat liberation were reduced 62-70% in DCM-F (p < 0.03). The crossbridge force-time integral (FTIXBr) was calculated from these measurements and was shown to increase 40% while the amount and rate of calcium cycled per beat was reduced 70%. As a result of these changes in the contractile and excitation-contraction coupling systems in DCM-F, the force-frequency relationship was significantly blunted while the power output was markedly reduced. These fundamental alterations account for the substantial ventricular dysfunction found in the dilated cardiomyopathic failing heart.
Alpert
N R
NR
Department of Molecular Physiology and Biophysics, University of Vermont College of Medicine, Burlington 05405, USA.
Mulieri
L A
LA
D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction; D007700:Kinetics; D009200:Myocardial Contraction; D012518:Sarcomeres / Q000502:physiology; D013816:Thermodynamics; D018754:Ventricular Dysfunction / Q000503:physiopathology*
D002118:Calcium