title: Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.
abstract: Overexpression of cardiac sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) has been suggested as a strategic intervention for cardiac failure. However, its benefit in wild-type (WT) rats with normal SERCA2a levels seems to be small. To investigate whether it would be beneficial in a cardiac failure model with down-regulated SERCA2a levels, we made a cardiac hypertrophy model using isoproterenol infusion (1.2mgkg(-1)day(-1) for 1 or 4weeks; TG-ISO1w and TG-ISO4w, respectively) in SERCA2a transgenic (TG) rats and compared these rats with littermate WT rats that underwent the same treatments (WT-ISO1w and WT-ISO4w). We analyzed the left ventricular (LV) mechanoenergetics in the excised heart using our original cross-circulation system. The downward shift of curvilinear LV end-systolic pressure-volume relations (ESPVRs) observed in WT-ISO4w rats was abolished in TG-ISO4w rats. The slope and VO2 intercept of the VO2 (myocardial oxygen consumption per beat)-PVA (systolic pressure-volume area: total mechanical energy per beat) linear relation did not differ in any of the groups. The most important finding was a significantly smaller O2 cost of LV contractility in the TG-ISO4w group, which means that less O2 is needed to exert the same LV contractility, compared with the other groups. The increased ratio of SERCA2a/phospholamban returned to the level of the WT-control group only in the TG-ISO4w group. Longer-term up-regulation of mitochondrial transcription factor A for genes of mitochondrial enzymes producing ATP was observed in TG rats. In conclusion, longer-term overexpression of SERCA2a will be beneficial in the present cardiac failure model with down-regulated SERCA2a levels.
authors: Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors: Shinichi
authors: S
authors: Mitsuyama
authors: Daisuke
authors: D
authors: Takeshita
authors: Koji
authors: K
authors: Obata
authors: Guo-Xing
authors: GX
authors: Zhang
authors: Miyako
authors: M
authors: Takaki
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000517:prevention & control* / Q000628:therapy*; D007545:Isoproterenol / Q000633:toxicity*; D008297:Male; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007545:Isoproterenol