[Energy utility of failing heart].
We investigated left ventricular (LV) mechanoenergetics in acute and chronic failing hearts, induced by high Ca(2+), ischemic-reperfusion injury, diabetes mellitus (DM), and hypothyroidism, using cross-circulated excised rat heart preparations. After high Ca(2+) or ischemic-reperfusion, there was a contractile failure associated with a parallel downward shift of the linear relation between myocardial O(2) consumption per beat (VO(2)) and systolic pressure-volume area (PVA). This result indicated a decrease in VO(2) for total Ca(2+) handling in E-C coupling. We found proteolysis of a cytoskeletal protein, alpha-fodrin. A calpain inhibitor significantly suppressed contractile failure, decreased VO(2) for total Ca(2+) handling, and membrane alpha-fodrin degradation. In DM, the LV relaxation rate was significantly slower, resulting in the decreased O(2) consumption per min for total Ca(2+) handling in E-C coupling. In hypothyroidism, there were systolic and diastolic failures associated with the decreased O(2) consumption per beat for total Ca(2+) handling in E-C coupling. The protein level of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2) was significantly lower in DM and hypothyroidism. We conclude that suppression of O(2) consumption for total Ca(2+) 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.
Yoshikawa
Yoshiro
Y
Department of Surgery III, Nara Medical University, Kashihara, Japan. yyoshiro@naramed-u.ac.jp
Takaki
Miyako
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D006333:Heart Failure / Q000378:metabolism*; D007037:Hypothyroidism / Q000150:complications / Q000378:metabolism; D051381:Rats; D016277:Ventricular Function, Left / Q000502:physiology*
D000252:Calcium-Transporting ATPases; D002118:Calcium