Energy utility of failing heart.
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Accession number;04A0131241
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| Title;Energy utility of failing heart. |
| Author;
YOSHIKAWA YOSHIRO
(Nara Med. Univ.)
TAKAKI MIYAKO
(Nara Med. Univ.)
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Journal Title;Folia Pharmacologica Japonica
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Journal Code:G0740A
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ISSN:0015-5691
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VOL.123;NO.2;PAGE.77-86(2004)
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| Figure&Table&Reference;FIG.8, REF.41 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We investigated left ventricular (LV) mechanoenergetics in acute and chronic failing hearts, induced by high Ca2+, ischemic-reperfusion injury, diabetes mellitus (DM), and hypothyroidism, using cross-circulated excised rat heart preparations. After high Ca2+ or ischemic-reperfusion, there was a contractile failure associated with a parallel downward shift of the linear relation between myocardial O2 consumption per beat (VO2) and systolic pressure-volume area (PVA). This result indicated a decrease in VO2 for total Ca2+ handling in E-C coupling. We found proteolysis of a cytoskeletal protein, .ALPHA.-fodrin. A calpain inhibitor significantly suppressed contractile failure, decreased VO2 for total Ca2+ handling, and membrane .ALPHA.-fodrin degradation. In DM, the LV relaxation rate was significantly slower, resulting in the decreased O2 consumption per min for total Ca2+ handling in E-C coupling. In hypothyroidism, there were systolic and diastolic failures associated with the decreased O2 consumption per beat for total Ca2+ handling in E-C coupling. The protein level of sarcoplasmic reticulum Ca2+ ATPase (SERCA2) was significantly lower in DM and hypothyroidism. We conclude that suppression of O2 consumption for total Ca2+ handling, mainly utilized by SERCA2, is a major cause of failing hearts, mediated through degradation of membrane .ALPHA.-fodrin via activation of calpain or suppressed expression of SERCA2. (author abst.) |
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