Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts

Abstract

The aim of the present study was to evaluate specifically left ventricular (LV) function in rat hearts as they transition from the normal to hypertrophic state and back to normal. Either isoproterenol (1.2 and 2.4 mg.kg(-1).day(-1) for 3 days; Iso group) or vehicle (saline 24 microl.day(-1) for 3 days; Sa group) was infused by subcutaneous implantation of an osmotic minipump. After verifying the development of cardiac hypertrophy, we recorded continuous LV pressure-volume (P-V) loops of in situ ejecting hypertrophied rat hearts. The curved LV end-systolic P-V relation (ESPVR) and systolic P-V area (PVA) were obtained from a series of LV P-V loops in the Sa and Iso groups 1 h or 2 days after the removal of the osmotic minipump. PVA at midrange LV volume (PVA(mLVV)) was taken as a good index for LV work capability (13, 15, 20, 21). However, in rat hearts during remodeling, whether PVA(mLVV) is a good index for LV work capability has not been determined yet. In the present study, in contrast to unchanged end-systolic pressure at midrange LV volume, PVA(mLVV) was significantly decreased by isoproterenol treatment relative to saline; however, these measurements were the same 2 days after pump removal. Simultaneous treatment with a beta(1)-blocker, metoprolol (24 mg.kg(-1).day(-1)), blocked the formation of cardiac hypertrophy and thus PVA(mLVV) did not decrease. The reversible changes in PVA(mLVV) reflect precisely the changes in LV work capability in isoproterenol-induced hypertrophied rat hearts mediated by beta(1)-receptors. These results indicate that the present approach may be an appropriate strategy for evaluating the effects of antihypertrophic and antifibrotic modalities.

Increased O2 consumption in excitation–contraction coupling in hypertrophied rat heart slices related to increased Na+–Ca2+ exchange activity

“…Cell size, measured with area of myocyte, was also significantly larger in HYP than the one of CONT. These data are substantially the same as those previously reported by us [10].…”

“…Distinct collagen accumulation was confirmed in the HYP slices used in the present study, as shown by previous papers including ours [9,10]. Our data also indicated that collagen contents measured by hydroxyproline methods in HYP (1.69 ± 0.21% collagen/LV dry weight; n = 6) were significantly (P \ 0.05) larger than those in CONT (1.33 ± 0.23% collagen/LV dry weight; n = 5), though the difference was small.…”

“…So far, various mechanisms for this remodeling have been proposed [5][6][7][8][9]. We have recently reported that 3-day subcutaneous infusion of isoproterenol to rats induced cardiac hypertrophy with unchanged left ventricular (LV) systolic and diastolic function that was reversible to the control levels after the cessation of infusion [10,11]. In this model, a significant decrease of mechanical work due to the decrease of LVV (LV volume) was observed.…”

“…-ATPase (SERCA2), phospholamban (PLB) and phosphorylated Ser 16 (phospho-ser 16 ) PLB (p-PLB) in this model were also decreased, suggesting that the Ca 2? -handling of the cardiac myocyte was already altered [10,11]. However, functional changes of molecules associated with the Ca 2?…”

Effects of a Novel Histone Deacetylase Inhibitor, N-(2-Aminophenyl) Benzamide, on a Reversible Hypertrophy Induced by Isoproterenol in In Situ Rat Hearts

“…Accordingly, we have proposed that PVA at midrange LV volume (PVA mLVV ) is a good mechanoenergetic index to evaluate LV function in the in situ normal rat heart (1 -3). Furthermore, we have validated the accuracy of the measurement of LV volume (LVV) in the in situ hypertrophic rat heart with a conductance catheter method (4). Using this method, we found that the changes in PVA mLVV sensitively reflected the formation and reversibility of isoproterenolinduced cardiac hypertrophy mediated by β 1 -receptor stimulation (4).…”