著者

Atsushi Sugiyama Sue Duval Yuji Nakamura Katsunori Yoshihara Demetris Yannopoulos

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.80, no.10, pp.2124-2132, 2016-09-23 (Released:2016-09-23)

参考文献数

42

被引用文献数

7 22

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Background:The quality of cardiopulmonary resuscitation (CPR) has been recently shown to affect clinical outcome. The Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation Impedance Valve and Early Versus Delayed Analysis (PRIMED) trial showed no differences in outcomes with an active vs. sham impedance threshold device (ITD), a CPR adjunct that enhances circulation. It was hypothesized the active ITD would improve survival with favorable neurological outcomes in witnessed out-of-hospital cardiac arrest patients when used with high-quality CPR.Methods and Results:Using the publicly accessible ROC PRIMED database, a post-hoc analysis was performed on all witnessed subjects with both compression rate and depth data (n=1,808) who received CPR within the study protocol definition of adequate CPR quality (compression rate 80–120/min and depth 4–6 cm; n=929). Demographics were similar between sham and active ITD groups. In witnessed subjects who received quality CPR, survival with favorable neurological function was 11.9% for the active ITD subjects (56/470) vs. 7.4% for the sham (34/459) (odds ratio 1.69 [95% confidence interval 1.08, 2.64]). There were no statistically significant differences for this primary outcome when CPR was performed outside the boundaries of the definition of adequate CPR quality. Multivariable models did not change these associations.Conclusions:An active ITD combined with adequate-quality conventional CPR has the potential to significantly improve survival after witnessed cardiac arrest. (Circ J 2016; 80: 2124–2132)

著者

Nobuyuki Suzuki Ryuichi Kambayashi Ai Goto Hiroko Izumi-Nakaseko Yoshinori Takei Atsuhiko T Naito Atsushi Sugiyama

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.48, no.12, pp.645-654, 2023 (Released:2023-12-01)

参考文献数

27

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Antiparasitic ivermectin has been reported to induce cardiovascular adverse events, including orthostatic hypotension, tachycardia and cardiopulmonary arrest, of which the underlying pathophysiology remains unknown. Since its drug repurposing as an antiviral agent is underway at higher doses than those for antiparasitic, we evaluated the cardiovascular safety pharmacology of ivermectin using isoflurane-anesthetized beagle dogs (n=4). Ivermectin in doses of 0.1 followed by 1 mg/kg was intravenously infused over 10 min with an interval of 20 min, attaining peak plasma concentrations of 0.94 ± 0.04 and 8.82 ± 1.25 μg/mL, which were 29-31 and 276-288 times higher than those observed after its antiparasitic oral dose of 12 mg/body, respectively. The latter peak concentration was > 2 times greater than those inhibiting proliferation of dengue virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and hepatitis B virus in vitro. Ivermectin decreased heart rate without altering mean blood pressure, suggesting that ivermectin does not cause hypotension or tachycardia directly. Ivermectin hardly altered atrioventricular nodal or intraventricular conduction, indicating a lack of inhibitory action on Ca2+ or Na+ channel in vivo. Ivermectin prolonged QT interval/QTcV in a dose-related manner and tended to slow the repolarization speed in a reverse frequency-dependent manner, supporting previously described its IKr inhibition, which would explain Tpeak-Tend prolongation and heart-rate reduction in this study. Meanwhile, ivermectin did not significantly prolong J-Tpeakc or terminal repolarization period, indicating torsadogenic potential of ivermectin leading to the onset of cardiopulmonary arrest would be small. Thus, ivermectin has a broad range of cardiovascular safety profiles, which will help facilitate its drug repurposing.

著者

Kazutaka Aonuma Tsuyoshi Shiga Hirotsugu Atarashi Kosuke Doki Hirotoshi Echizen Nobuhisa Hagiwara Junichi Hasegawa Hideharu Hayashi Kenzo Hirao Fukiko Ichida Takanori Ikeda Yorinobu Maeda Naoki Matsumoto Toshiyuki Sakaeda Wataru Shimizu Mitsuru Sugawara Kyoichi Totsuka Yoshimasa Tsuchishita Kazuyuki Ueno Eiichi Watanabe Masayuki Hashiguchi Sumio Hirata Hidefumi Kasai Yoshiaki Matsumoto Akihiko Nogami Yukio Sekiguchi Tokuko Shinohara Atsushi Sugiyama Naokata Sumitomo Atsushi Suzuki Naohiko Takahashi Eiji Yukawa Masato Homma Minoru Horie Hiroshi Inoue Hiroshi Ito Takanori Miura Tohru Ohe Kimikazu Shinozaki Kazuhiko Tanaka on behalf of the Japanese Circulation Society and the Japanese Society of Therapeutic Drug Monitoring Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.81, no.4, pp.581-612, 2017-03-24 (Released:2017-03-24)

参考文献数

185

被引用文献数

33

著者

Yukiko Yamazaki-Hashimoto Yuji Nakamura Hiroshi Ohara Xin Cao Ken Kitahara Hiroko Izumi-Nakaseko Kentaro Ando Hiroshi Yamazaki Takanori Ikeda Junichi Yamazaki Atsushi Sugiyama

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.40, no.1, pp.33-42, 2015-02-01 (Released:2014-12-18)

参考文献数

39

被引用文献数

9 11

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Fluvoxamine is one of the typical selective serotonin-reuptake inhibitors. While its combined use with QT-prolonging drugs has been contraindicated because of the increase in plasma concentrations of such drugs, information is still limited whether fluvoxamine by itself may directly prolong the QT interval. We examined electropharmacological effects of fluvoxamine together with its pharmacokinetic profile by using the halothane-anesthetized dogs (n = 4). Fluvoxamine was intravenously administered in three escalating doses of 0.1, 1 and 10 mg/kg over 10 min with a pause of 20 min between the doses. The low dose provided therapeutic plasma drug concentration, whereas the middle and high doses attained approximately 10 and 100 times of the therapeutic ones, respectively. Supra-therapeutic concentration of fluvoxamine exerted the negative chronotropic, inotropic and hypotensive effects; and suppressed the atrioventricular nodal and intraventricular conductions, indicating inhibitory actions on Ca2+ and Na+ channels, whereas it delayed the repolarization in a reverse use-dependent manner, reflecting characteristics of rapidly activating delayed rectifier K+ current channel-blocking property. Fluvoxamine prolonged the terminal repolarization phase at 100 times higher concentration than the therapeutic, indicating its proarrhythmic potential. Thus, fluvoxamine by itself has potential to directly induce long QT syndrome at supra-therapeutic concentrations.

著者

Takeshi Wada Mihoko Hagiwara-Nagasawa Ryuichi Kambayashi Ai Goto Koki Chiba Yoshio Nunoi Hiroko Izumi-Nakaseko Tadashi Koga Akio Matsumoto Yuji Nakazato Keith G. Lurie Atsushi Sugiyama

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.85, no.10, pp.1885-1891, 2021-09-24 (Released:2021-09-24)

参考文献数

29

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Background:Effects of rapid electrical defibrillation and β-blockade on coronary ischemia/reperfusion-induced ventricular fibrillation (VF) during cardiopulmonary resuscitation (CPR) remain unknown.Methods and Results:After induction of VF by 30 min of ischemia followed by reperfusion, animals were treated with defibrillation alone (Group A, n=13), 2 min of open-chest cardiac massage followed by defibrillation (Group B, n=11), or the same therapy to Group B with propranolol (1 mg/kg, i.v.) treatment before ischemia/reperfusion (Group C, n=11). If return of spontaneous circulation (ROSC) was not attained, each therapy was repeated ≤3 times (Set-1). When ROSC was not obtained within Set-1, cardiac massage was applied to all animals followed by defibrillation, which was repeated ≤3 times (Set-2). ROSC after Set-1 was 8% in Group A, 82% in Group B and 82% in Group C, whereas that after Set-2 was 62% in Group A, 100% in Group B and 82% in Group C. Each animal with ROSC in Groups A (n=8) and B (n=11) showed sinus rhythm, whereas those in Group C (n=9) had sinus rhythm (n=5), atrial fibrillation (n=1), accelerated idioventricular rhythm (n=2) and atrioventricular block (n=1). Post ROSC heart rate and mean arterial pressure were significantly lower in Group C.Conclusions:Cardiac massage increased the likelihood of ROSC vs. rapid defibrillation, but β-blocker pretreatment may worsen hemodynamics and electrical stability after ROSC.

著者

Xin Cao Yuji Nakamura Takeshi Wada Hiroko Izumi-Nakaseko Kentaro Ando Atsushi Sugiyama

出版者

日本毒性学会

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.41, no.3, pp.439-447, 2016-06-01 (Released:2016-05-17)

参考文献数

21

被引用文献数

13

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Since amantadine-induced long QT syndrome has been clinically reported, we investigated its electropharmacological effects to estimate the extent of proarrhythmic risk by using the halothane-anesthetized beagle dogs (n = 4). Amantadine in doses of 0.1, 1 and 10 mg/kg was infused over 10 min with a pause of 20 min under the monitoring of multiple cardiovascular variables. J-Tpeak and Tpeak-Tend were separately measured on the lead II electrocardiogram to precisely analyze the net balance between inward and outward current modifications by amantadine. The low dose increased the ventricular contractile force, but suppressed the intraventricular conduction. The middle dose prolonged the QT interval besides enhancing the changes induced by the low dose. The high dose increased the mean blood pressure, left ventricular end-diastolic pressure and total peripheral resistance, and accelerated the atrioventricular nodal conduction, but decreased the cardiac output besides enhancing the changes induced by the middle dose. A reverse use-dependence was confirmed in the repolarization delay. Amantadine hardly affected the J-Tpeak, but prolonged the Tpeak-Tend. Amantadine can be considered to stimulate Ca2+ channel but inhibit Na+ and K+ channels in the in situ heart. J-Tpeak and Tpeak-Tend analysis suggests that amantadine may possess modest risk for arrhythmia.