著者

Takahiro Tokuhisa Masafumi Yano Masakazu Obayashi Toshiyuki Noma Mamoru Mochizuki Tetsuro Oda Shinichi Okuda Masahiro Doi Jinyao Liu Yasuhiro Ikeda Takeshi Yamamoto Tomoko Ohkusa Masunori Matsuzaki

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.70, no.6, pp.777-786, 2006 (Released:2006-05-25)

参考文献数

42

被引用文献数

18 20

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Background The Ca2+ regulatory proteins in the sarcoplasmic reticulum (SR) play a key role in the pathogenesis of heart failure. In the present study the effect of chronic β-receptor-stimulation on cardiac and SR functions was assessed, with or without angiotensin-II receptor antagonist treatment recently reported to have anti-β-adrenergic activity. Methods and Results Rats were treated with isoproterenol with (+) or without (-) candesartan (CAN) and then SR vesicles were isolated from the left ventricular muscle. Both Ca2+-uptake and the amount of SR Ca2+-ATPase were significantly lower in the CAN (-) group than in the shams, but those were almost normally restored in the CAN (+). Although the level of the protein kinase A (PKA)-phosphorylation of the SR Ca2+ release channel, known as the ryanodine receptor (RyR2), was elevated in the CAN (-), no Ca2+-leak was detected. However, SIN-1 (O2 - donor) induced Ca2+-leak in the CAN (-) at a 10-fold lower dose than in the sham and CAN (+). In cardiomyocytes, SIN-1 decreased cell shortening and the peak Ca2+ transient and prolonged time from peak to 70% decline in CAN (-), again at 10-fold lower dose than in the sham and CAN (+). Conclusion Chronic β-receptor-stimulation did not induce any Ca2+-leak from the SR, whereas Ca2+-leak was easily induced when oxidative stress was applied to the PKA-phosphorylated RyR2. Candesartan not only improved Ca2+-uptake, but also prevented PKA-phosphorylation, rendering the SR less susceptible to Ca2+-leak. (Circ J 2006; 70: 777 - 786)

著者

Masashi Kanemoto Hiroko Kuhara Toru Ueda Takahiro Shinohara Takamasa Oda Fumiaki Nakao Toshiaki Kamei Yasuhiro Ikeda Takashi Fujii

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.78, no.11, pp.2651-2656, 2014-10-24 (Released:2014-10-24)

参考文献数

20

被引用文献数

3 13

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Background:This study evaluated whether measuring prothrombin time (PT) using particular reagents of interest predicted apixaban-associated anticoagulant activity in Japanese patients with non-valvular atrial fibrillation (NVAF).Methods and Results:Two reagents, Shinplastin Excel S and Coagpia PT-N, were used to evaluate PT under apixaban therapy. From June 2013 to February 2014, 103 NVAF patients were recruited, and PT was measured at 3 time points: (1) anytime in the outpatient clinic, (2) at peak, and (3) at trough. In spike-in experiments using pooled citrated normal human platelet-poor plasma with these PT reagents, apixaban prolonged PT values in a concentration-dependent manner. PT values significantly correlated between both reagents (r=0.97) in outpatients. PT values in outpatients taking 5-mg apixaban bid were significantly prolonged and had wide inter- and intraindividual variability. Peak values were significantly higher than trough values, with both values higher than normal. The dose change of apixaban from 5 mg bid to 2.5 mg bid in outpatients halved the degree of PT prolongation in each NVAF patient.Conclusions:The PT value measured by these specific reagents can predict apixaban-associated anticoagulant activity, although there is significant interpatient variability. (Circ J 2014; 78: 2651–2656)