Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

Takahashi, Shinji; Fujii, Yoshitaka; Hoshi, Takashi; Uemura, Akira; Miyabe, Masayuki; Toyooka, Hidenori

doi:10.1007/bf03019382

Can J Anesth/J Can Anesth

2003

DOI: 10.1007/bf03019382

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Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

Shinji Takahashi

Yoshitaka Fujii

Takashi Hoshi

et al.

Abstract: B Ba ac ck kg gr ro ou un nd d: : Clinical use of high dose beta-blocker therapy is limited by excessive negative inotropic effects. Previous studies suggest that milrinone may be of utility in limiting the inotropic but not the chronotropic effects of beta blockers. We examined the hemodynamic effects of co-administration of a new potent selective beta 1 blocker, landiolol, and milrinone in halothane-anesthetized dogs.M Me et th ho od ds s: : Eighteen adult mongrel dogs were anesthetized with 1.2 MAC halothan… Show more

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Cited by 7 publications

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“…Milrinone, an inhibitor of phosphodiesterase (PDE) III, increases the concentration of intracellular cyclic adenosine monophosphate (cAMP) by retarding the degradation of this molecule [1,22]. The modulation of intracellular cAMP by milrinone produces inotropic and chronotropic effects on the heart and relaxation of vessels in the absence of β-receptor stimulation [1,12,23]. Therefore, milrinone may produce beneficial effects even though myocardial β-receptors are downregulated during heart failure.…”

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Cardiovascular Effects of a Phosphodiesterase III inhibitor in the Presence of Carvedilol in Dogs

Uechi

Hori

Fujimoto

et al. 2006

The Journal of Veterinary Medical Science

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ABSTRACT. The aim of this study was to determine whether dobutamine, dopamine, or milrinone (a phosphodiesterase [PDE] III inhibitor) would support cardiac function that had been attenuated by administration of the β-blocker, carvedilol (0.2, 0.4, or 0.8 mg/kg). Hemodynamic and cardiac parameters including the heart rate (HR), left-ventricular fractional shortening (FS), and arterial pressure were measured in six healthy dogs without cardiac disease. Carvedilol did not affect FS or arterial pressure, but decreased the HR significantly. The positive inotropic and chronotropic responses to dobutamine and dopamine were attenuated by carvedilol, whereas arterial pressure was unaffected. Milrinone did not affect the HR and decreased arterial pressure, whereas FS was significantly greater both in the control and carvedilol-treated groups. Although milrinone affect the negative chronotropic effects of carvedilol, milrinone increased FS and prevented the decrease in arterial pressure. These results suggest that inhibition of PDE III preserves cardiac contractility and hemodynamic function in the presence of carvedilol.KEY WORDS: β-blocker, cardiac function, heart failure, inotropic agent.J. Vet. Med. Sci. 68(6): 549-553, 2006 Clinical studies on humans have shown that treatment of congestive heart failure with β-blockers can reduce mortality [4,5,10,16] by improving myocardial energy metabolism, reducing arrhythmia, reducing damage to cardiac myocytes, up-regulating β 1 receptor expression, and improving diastolic function [5]. However, cardiac function must be monitored carefully in heart failure patients who are undergoing treatment with β-blockers because such treatment is associated with side effects that include bradycardia, hypotension, and A-V node blocking [2,21].It has been established that sympathomimetic drugs such as dobutamine and dopamine may prevent acute heart failure and circulatory collapse. However, the down-regulation of myocardial β-receptors that occurs during heart failure leads to an attenuation of the chronotropic and inotropic effects of β-receptor agonists such as adrenaline, noradrenaline, dobutamine, and dopamine [3,7,9]. Milrinone, an inhibitor of phosphodiesterase (PDE) III, increases the concentration of intracellular cyclic adenosine monophosphate (cAMP) by retarding the degradation of this molecule [1,22]. The modulation of intracellular cAMP by milrinone produces inotropic and chronotropic effects on the heart and relaxation of vessels in the absence of β-receptor stimulation [1,12,23]. Therefore, milrinone may produce beneficial effects even though myocardial β-receptors are downregulated during heart failure. Presumably, the beneficial effects of milrinone also apply in situations in which β-receptors have been blocked by the administration of a β-The objective of this study was to determine whether dobutamine, dopamine, or milrinone could support cardiac function that had been attenuated by the administration of a β-blocker. To achieve the objective, the hemodynamic and cardia...

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confidence: 99%

Cardiovascular Effects of a Phosphodiesterase III inhibitor in the Presence of Carvedilol in Dogs

Uechi

Hori

Fujimoto

et al. 2006

The Journal of Veterinary Medical Science

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Age and sex-related differences in dose-dependent hemodynamic response to landiolol hydrochloride during general anesthesia

Mizuno

Yoshiya

Yokoyama

et al. 2007

Eur J Clin Pharmacol

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Retraction of articles written by Dr. Yoshitaka Fujii

Miller

2012

Can J Anesth/J Can Anesth

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On March 13 th , 2012, an Expression of Concern was posted in the Journal regarding 39 published articles written by Dr. Yoshitaka Fujii from Japan. A The notice explained that the Editorial Office had received an article submission entitled ''Effects of colforsin daropate on hypercapnic depression of diaphragmatic contractility in pentobarbitalanesthetized dogs''. The authors of the article are Yoshitaka Fujii MD and Aki Uemura MD from the First Department of Anesthesiology, Toho University School of Medicine in Tokyo, Japan. At the time the article was submitted, the editors of the Journal were aware of ongoing concerns regarding Dr. Fujii's work that extended over the previous two decades. Indeed, a Letter to the Editor by Kranke et al. 1 published in Anesthesia & Analgesia in 2000 raised serious concerns regarding the implausibility of data in 47 articles by Dr. Fujii published in five journals, including the Canadian Journal of Anesthesia, during the years 1994-99. In 13 of the articles cited by Kranke et al., the frequency of headache was reported as being identical in all groups, whereas this side effect differed by no more than one patient per group in the remaining eight papers. Statistical testing of the null hypothesis that the reported identical incidences could have occurred by chance vs the alternative hypothesis that an underlying reason led to such identical results led Kranke et al. to their conclusion that ''there must be an underlying influence causing such incredibly nice data reported by Fujii et al.'' 1 In retrospect, we deeply regret that the affected journals did not pursue these concerns at that time. Looking back to 2011, I alerted Dr. Ryoichi Ochiai, Professor of Anesthesiology at Toho University School of Medicine, to concerns regarding the implausibility of certain elements of the data presented in Dr. Fujii's manuscript on colforsin daropate submitted to the Journal. This notification triggered the launch of an internal investigation at Toho University. I was subsequently advised that Dr. Fujii's article had no ethically approved protocol, and furthermore, there would be no means to prove the authenticity of the data or the validity of the study itself. The Journal rejected this article as a result of the departmental investigation, leaving the extent of further actions to be determined by the University. Shortly thereafter, a more extensive review of Dr. Fujii's work was launched by the Investigating Committee of the Faculty of Medicine at Toho University. The University Discipline Committee's findings were released in March 2012 and referred to studies (Appendix, available as Electronic Supplementary Material) published in other journals that had been conducted without Ethics Committee approval. In its statement, the University exonerated co-author Dr. Michiyo Itakura. Toho University subsequently organized a Disciplinary Committee which ruled disciplinary dismissal appropriate, and Dr. Fujii was summarily dismissed on February 29, 2012. In March 2012, a detailed and innovative ana...

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Milrinone attenuates the negative inotropic effects of landiolol in halothane-anesthetized dogs

Cited by 7 publications

References 17 publications

Cardiovascular Effects of a Phosphodiesterase III inhibitor in the Presence of Carvedilol in Dogs

Cardiovascular Effects of a Phosphodiesterase III inhibitor in the Presence of Carvedilol in Dogs

Age and sex-related differences in dose-dependent hemodynamic response to landiolol hydrochloride during general anesthesia

Retraction of articles written by Dr. Yoshitaka Fujii

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