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

Department of Physiology II, Nara Medical University, Kashihara, Nara 634-8521, Japan

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 µl·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 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 ₁-receptors. These results indicate that the present approach may be an appropriate strategy for evaluating the effects of antihypertrophic and antifibrotic modalities.

left ventricular volumetry; conductance catheter; collagen; systolic pressure-volume area

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