title: Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.
abstract: Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.
authors.affiliation: Department of Cardiac Surgery, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655 Japan. takeuchik-sur@h.u-tokyo.ac.jp
authors.forename: Koh
authors.initials: K
authors.lastname: Takeuchi
authors.forename: M
authors.initials: M
authors.lastname: Minakawa
authors.forename: M
authors.initials: M
authors.lastname: Otaki
authors.forename: S
authors.initials: S
authors.lastname: Odagiri
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: A
authors.initials: A
authors.lastname: Murakami
authors.forename: H
authors.initials: H
authors.lastname: Yaku
authors.forename: N
authors.initials: N
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D000252:Calcium-Transporting ATPases / Q000494:pharmacology*; D004195:Disease Models, Animal; D006352:Heart Ventricles / Q000473:pathology; D006980:Hyperthyroidism / Q000150:complications*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013963:Thyroid Hormones / Q000494:pharmacology*; D014285:Triiodothyronine, Reverse / Q000008:administration & dosage
chemical_list: C506948:Atp2a2 protein, rat; D013963:Thyroid Hormones; D014285:Triiodothyronine, Reverse; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases