Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.

Overexpression of cardiac sarcoplasmic reticulum Ca2 +-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 (1.2 mg kg- 1 day- 1 for 1 or 4 weeks; 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.;博士(医学)・甲619号・平成26年3月17日;開始ページ : 95;終了ページ : 106;PubMed番号 : http://www.ncbi.nlm.nih.gov/pubmed/23458361

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書名 Left ventricular mechanical and energetic changes in long-term isoproterenol-induced hypertrophied hearts of SERCA2a transgenic rats.
著作者等 International Society for Heart Research
Obata Koji
Takaki Miyako
Takeshita Daisuke
Zhang Guo-Xing
Mitsuyama Shinichi
書名別名 SERCA2a過剰発現ラットにおけるイソプロテレノール持続投与誘導肥大心の左室力学的エネルギー学的性質の変化
出版元 Academic Press/Elsevier
刊行年月 1970-
ISSN 00222828
NCID AA00702819
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言語 英語
出版国 イギリス
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