Reversible effects of isoproterenol-induced hypertrophy on in situ left ventricular function in rat hearts.
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.
Kitagawa
Yutaka
Y
Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Yamashita
Daisuke
D
Ito
Haruo
H
Takaki
Miyako
M
D000318:Adrenergic beta-Agonists; D000818:Animals; D015153:Blotting, Western; D006328:Cardiac Catheterization; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D055590:Electromagnetic Phenomena; D045268:Flowmeters; D007545:Isoproterenol; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013318:Stroke Volume; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D007545:Isoproterenol