Cardiac dysfunction in terms of left ventricular mechanical work and energetics in hypothyroid rats.
We hypothesized that cardiac dysfunction in hypothyroidism is mainly caused by the impairment of Ca(2+) handling in excitation-contraction coupling. To prove this hypothesis, we investigated left ventricular (LV) mechanical work and energetics without interference of preload and afterload in an excised, blood-perfused whole heart preparation from hypothyroid rats. We found that LV inotropism and lusitropism were significantly depressed, and these depressions were causally related to decreased myocardial oxygen consumption for Ca(2+) handling and for basal metabolism. The oxygen costs of LV contractility for Ca(2+) and for dobutamine in the hypothyroid rats did not differ from those in age-matched normal rats. The expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) significantly decreased and that of phospholamban significantly increased. The present results revealed that changes in LV energetics associated with decreased mechanical work in hypothyroid rats are mainly caused by the impairment of Ca(2+) uptake via SERCA2. We conclude that the impairment of Ca(2+) uptake plays an important role in the pathogenesis of cardiac dysfunction in hypothyroidism.
Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Yoshimi
Y
Ohga
Susumu
S
Sakata
Chikako
C
Takenaka
Takehisa
T
Abe
Tsuyoshi
T
Tsuji
Shigeki
S
Taniguchi
Miyako
M
Takaki
D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume; D001835:Body Weight; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D004734:Energy Metabolism; D007037:Hypothyroidism / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D010101:Oxygen Consumption; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018487:Ventricular Dysfunction, Left; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C506948:Atp2a2 protein, rat