MYOCYTE REORGANIZATION IN HYPERTROPHIED AND FAILING HEARTS

In hypertrophied and failing hearts there are major changes in the ove rall contractile performance We present a review of our previous work relating the alterations in myocardial force work, power and relaxatio n, 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 cardi omyopathy) heart were used in these studies. Myocardial peak twitch te nsion (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 m echanical 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 preparati ons (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, h uman 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 c ross-bridge force-time integral (pNs, pico Newton seconds) was increas ed in ah experimental preparations (dilated cardiomyopathy, 138%; volu me overload 175%; pressure overload, 253%), while in each of the exper imental 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 i n these hearts and the inadequate cardiac output in the failing hearts are attributed to these documented changes in the contractile and exc itation contraction coupling systems.