MYOCYTE REORGANIZATION IN HYPERTROPHIED AND FAILING HEARTS

In hypertrophied and failing hearts there are major changes in the overall contractile performance We present a review of our previous work relating the alterations in myocardial force work, power and relaxation, that lead to changes in overall ventricular performance, to changes in the actin-myosin cross-bridge cycle characteristics along with the degree of activation and inactivation (calcium cycling). Tissues from hypertrophied rabbit and failing human (volume overload dilated cardiomyopathy) heart were used in these studies. Myocardial peak twitch tension (mN.mm(-2) was reduced in dilated cardiomyopathy (human) (25.9 +/- 3.9 vs 13.9 +/- 2.0, 37 degrees C), volume overload (human) (44.0 +/- 11.7 vs 19.9 +/- 3.7, 21 degrees C) and pressure overload (rabbit) (46.1 +/- 2.6 vs 41.7 +/- 5.0, 21 degrees C). We used myothermal and mechanical data to analyse the average cross-bridge force time integral and the amount of calcium cycled pet gram per bent. Tension-dependent heat (mJ.g(-1)) (TIH) (cross-bridge cycling) and tension-independent heat (mJ.g(-1) (TIH) were reduced in all of the experimental preparations (dilated cardiomyopathy, human , 37 degrees C: TDH, 3.39 +/- 0.59 vs 1.34 +/- 0.22; TIH, 0.51 0.02 vs 0.16 +/- 0.03) (volume overload, human 21 degrees C: TDH, 7.23 +/- 2.22 vs 1.92 +/- 0.25; TIH, 0.75 +/- 0.19 vs 0.39 0.04) (pressure overload rabbit, 21 degrees C: TDH, 6.60 +/- 0.75 vs 3.05 +/- 0.46; TIH, 1.00 +/- 0.17 vs 0.41 +/- 0.08). The cross-bridge force-time integral (pNs, pico Newton seconds) was increased in ah experimental preparations (dilated cardiomyopathy, 138%; volume overload 175%; pressure overload, 253%), while in each of the experimental preparations, the amount of calcium cycled (nmoles.beat-g) is reduced (expressed as % control) (dilated cardiomyopathy, 36%; volume overload 53%; pressure overload 46%). The decrease in power observed in these hearts and the inadequate cardiac output in the failing hearts are attributed to these documented changes in the contractile and excitation contraction coupling systems.