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

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
Yasuaki Wada Kazuya Murata Takeo Tanaka Yoshio Nose Chikage Kihara Kosuke Uchida Shinichi Okuda Takehisa Susa Yukari Kishida Masunori Matsuzaki
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.3, pp.675-681, 2012 (Released:2012-02-24)
参考文献数
24
被引用文献数
24 28

Background: The time interval between the onset of early transmitral flow velocity (E) and that of early diastolic mitral annular velocity (e') (TE-e') is a good predictor of elevated left ventricular (LV) filling pressure in patients with sinus rhythm. Although the evaluation of LV filling pressure using E/e' has been challenging in atrial fibrillation (AF), the usefulness of TE-e' is unknown. Methods and Results: E and e' were simultaneously recorded using dual Doppler echocardiography in 45 AF patients (30 men; mean age, 69±9 years). E/e' and TE-e' were calculated and compared with the pulmonary capillary wedge pressure (PCWP), which was measured invasively. E/e' and TE/e' correlated with PCWP (E/e', r=0.57, P<0.001; TE-e', r=0.77, P<0.001). Using receiver operating characteristic analysis, the optimal cut-off for TE-e' was 34ms (sensitivity, 95%; specificity, 88%) and that for E/e' was 14.6 (sensitivity, 50%; specificity, 84%) in order to predict >12-mmHg PCWP. When the combined cut-offs of TE-e' >34ms and E/e' >14.6 were used, the sensitivity and specificity of predicting elevated PCWP were improved to 100% and 88%, respectively. Conclusions: In AF patients, the simultaneous recording of E and e' using dual Doppler echocardiography and the analysis of TE-e', in addition to E/e', improved the accuracy of evaluation of LV filling pressure. (Circ J 2012; 76: 675-681)