How the Deuteration of Dronedarone Can Modify Its Cardiovascular Profile: In Vivo Characterization of Electropharmacological Effects of Poyendarone, a Deuterated Analogue of Dronedarone.

How the Deuteration of Dronedarone Can Modify Its Cardiovascular Profile: In Vivo Characterization of Electropharmacological Effects of Poyendarone, a Deuterated Analogue of Dronedarone. Cardiovasc Toxicol. 2020 Jan 02;: Authors: Kambayashi R, Hagiwara-Nagasawa M, Kondo Y, Yeo ZJ, Goto A, Chiba K, Nunoi Y, Izumi-Nakaseko H, Leow JWH, Venkatesan G, Matsumoto A, Chan ECY, Sugiyama A Abstract Since deuterium replacement has a potential to modulate pharmacodynamics, pharmacokinetics and toxicity, we developed deuterated dronedarone; poyendarone, and assessed its cardiovascular effects. Poyendarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s was intravenously administered to the halothane-anesthetized dogs (n = 4), which provided peak plasma concentrations of 108 ± 10 and 1120 ± 285 ng/mL, respectively. The 0.3 mg/kg shortened the ventricular repolarization period. The 3 mg/kg transiently increased the heart rate at 5 min but decreased at 45 min, and elevated the total peripheral vascular resistance and left ventricular preload, whereas it reduced the mean blood pressure at 5 min, left ventricular contractility and cardiac output. The transient tachycardic action is considered to be induced by the hypotension-induced, reflex-mediated increase of sympathetic tone. The 3 mg/kg delayed both intra-atrial and intra-ventricular conductions, indicating Na+ ch...
Source: Cardiovascular Toxicology - Category: Cardiology Authors: Tags: Cardiovasc Toxicol Source Type: research

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Cardiac microdialysis allows the assessment of cardiac efferent vagal nerve activity from myocardial interstitial acetylcholine (ACh) levels with minimal influence on the neural control of the heart; however, a total picture of the baroreflex-mediated myocardial interstitial ACh release including the threshold and saturation pressures has yet to be quantified. In eight anesthetized Wistar –Kyoto rats, we implanted microdialysis probes in the left ventricular free wall and measured the myocardial interstitial ACh release simultaneously with efferent sympathetic nerve activity (SNA) during a carotid sinus baroreceptor ...
Source: Autonomic Neuroscience: Basic and Clinical - Category: Neuroscience Authors: Source Type: research
The science of transitional states of consciousness is reviewed. Despite intensive study, determining the subjective experience of animals during transitional states of consciousness remains inherently limited. Until better assessment tools become available, behavior-based observations, such as loss of righting reflex/loss of posture, remain among our most useful guides to the onset of unconsciousness in animals. To minimize potential animal suffering and to ensure a truly unconscious state is unambiguously achieved, a state of general anesthesia relying on gamma amino butyric acid type A agonists or N-methyl-d-aspartate a...
Source: Veterinary Clinics of North America: Small Animal Practice - Category: Veterinary Research Authors: Source Type: research
Conclusions Inability to induce anesthesia in lesioned animals using normally effective doses of etomidate, propofol, and pentobarbital suggests that the mesopontine tegmental anesthesia area is the effective target of these, but not necessarily all, GABAergic anesthetics upon systemic administration. Cortical and spinal functions are likely suppressed by recruitment of dedicated ascending and descending pathways rather than by direct, distributed drug action.Editor ’s PerspectiveWhat We Already Know about This TopicLesions of the mesopontine tegmental anesthesia area in the brainstem render rats strongly insensitive...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
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Source: European Journal of Anaesthesiology - Category: Anesthesiology Tags: Correspondence Source Type: research
Authors: Madirazza K, Pecotic R, Pavlinac Dodig I, Valic M, Dogas Z Abstract Activation of the sympathetic nervous system plays an important role in the pathophysiology of sleep-related breathing disorders. The aim of the present study was to examine the effects of different levels of hypercapnia in the presence of various background oxygen levels on the magnitude of sympathoexcitation, measured by the renal sympathetic nerve activity (RSNA) in the acute intermittent hypercapnia (AIHc) rat model. The study was conducted on 56 urethane-anesthetized, vagotomized and mechanically ventilated Sprague-Dawley rats (n = 7/...
Source: Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Tags: J Physiol Pharmacol Source Type: research
We describe the case of a female patient proposed for laparoscopic bariatric surgery, conducted under an opioid-free anaesthesia protocol, the haemodynamic, ventilatory and analgesic control, and intra- and post-operative monitoring and complications.
Source: Indian Journal of Anaesthesia - Category: Anesthesiology Authors: Source Type: research
Jyotsna Punj, Snehitha MaradaIndian Journal of Anaesthesia 2020 64(2):148-150
Source: Indian Journal of Anaesthesia - Category: Anesthesiology Authors: Source Type: research
Aditi Jain, Aditi Mehta, Usha Singh, Vikas SainiIndian Journal of Anaesthesia 2020 64(2):163-165
Source: Indian Journal of Anaesthesia - Category: Anesthesiology Authors: Source Type: research
Conclusion: The KF played no significant role in the baroreflex, but could account for cardiovascular chemoreflex in urethane anesthetized rats. PMID: 31988857 [PubMed]
Source: BioImpacts - Category: Research Tags: Bioimpacts Source Type: research
Abstract PURPOSE: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. METHODS: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked im...
Source: Current Neurovascular Research - Category: Neurology Authors: Tags: Curr Neurovasc Res Source Type: research
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