Analysis of cradiac chromotropic responses to diazepam and bromazepam in conscious trained dogs

Gerold, M.; Cavero, I.; Riggenbach, Hans; Wall, Michael; Haeusler, Günther

doi:10.1016/0014-2999(76)90239-9

Cited by 20 publications

(16 citation statements)

References 11 publications

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“…The lack of effect on BP is consistent with what is observed in animal experimental studies [4, 5], but not with most human studies that reported a decrease in BP values [812, 14]. However, these latter findings are not comparable with our results, since human studies were generally carried out under acute paradigms, where the drug was administered to awaken patients or under stressful conditions and not before the physiologic nocturnal sleep.…”

Section: Discussioncontrasting

confidence: 51%

“…This suggests that the HR rise was not dependent by changes in baroreflex sensitivity, which some studies reported to be attenuated by diazepam [8, 22]. One possible explanation for the observed HR increase might be the reduction of vagal tone following diazepam administration [5, 6, 13, 15, 19]. Diazepam, which enhances the interaction between GABA and its receptor site, has been shown to potentiate the vagal inhibitory response [6, 13].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

et al. 2017

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Aim: To assess the effects of evening chronic administration of diazepam on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. Methods: This randomized double blind, cross-over study evaluated the effects of diazepam 5 mg or placebo, both ingested in the evening, on 24-h ambulatory BP and HR in healthy subjects aged 21–30. Results: A total of 30 subjects were included in the analysis. At the end of 4-week diazepam intake, an increase in 24-h HR mean values was found (+5.2 beats/min, p < 0.05). Analysis of subperiods showed that diazepam produced a 10.1% increase in night-time HR (+6.1 beats/min, p < 0.01) without affecting BP. A significant HR rise (+4.9 beats/min, p < 0.05) and SBP reduction (–3.8 mm Hg, p < 0.05) were observed in the morning hours. The HR increase persisted in day-time hours (+4.6 beats/min, p < 0.05), while BP values resulted unaffected. Conclusions: In healthy subjects, diazepam taken as a hypnotic agent induces a significant HR increase, possibly mediated by a decrease in vagal tone. This effect might be of clinical relevance due to the role that HR plays as an independent cardiovascular risk factor.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

et al. 2017

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“…Some of them could be implicated in the control of the central cardiovascular mechanisms (Bolme and Fuxe 1977). The latter explanations are similar to those of Gerold et al (1976), who reported that the origin of tachycardia was due to a central reduction of vagal tone and to a direct action on the cardiac pace-maker. These authors concluded that the central action was more pronounced.…”

Section: Discussionsupporting

confidence: 68%

“…During wakefulness, intravenotis injection of diazepam increased heart rate in non-anaesthetized cats (Rozonov 1976). Similar effect was observed after injections of high doses of bromazepam in dogs (Gerold et al 1976). In man, diazepam induced an increase in heart rate (Rao et al 1973;Allen et al 1976).…”

supporting

confidence: 64%

Effects of triazolam on heart rate level and on phasic cardiac response to noise during sleep

Libert¹,

Amoros²,

Muzet³

et al. 1988

Psychopharmacology

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The influence of triazolam on cardiac and respiratory activity of healthy male subjects was examined during nights disturbed by airplane noises and during undisturbed nights. Twenty-four subjects, divided into three groups of eight, slept in the laboratory for 7 nights (N0-N6). Following a double blind design, group A (control group) received a placebo every night. Group B received 0.25 mg triazolam and group C received 0.5 mg on nights N3, N4 and N5. On the other nights, they received a placebo. For all three groups, the nights N0, N3 and N5 were disturbed by 32 semi-randomly distributed airplane noises. Air and wall temperatures (20 degrees C) and air humidity (10 degrees C, 52%) were kept constant. Sleep measures, heart rate and respiratory rate were continuously recorded. Results showed that the largest dose of hypnotic drug produced an increase in tonic heart rate in the first part of each night throughout the treatment period (N3, N4, N5). When compared to baseline disturbed night N0, the phasic cardiac response to the noises was significantly attenuated on only the 1st treatment night (N3). Triazolam had no significant effect on nocturnal respiratory rate. No after-effects of the drug were observed for cardiac and respiratory activity on the withdrawal night (N6). The results suggest that, with regard to the drug action, there was either an increase in arousal threshold or a dissociation between long-lasting and short-lasting modifications of heart rate. Contrary to the single night attenuation of phasic cardiac responses, there was no drug tolerance for the hypnotic-related increase in tonic heart rate.

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“…had no influence on heart rate, but a rapid onset positive chronotropic effect was observed at higher doses (10 mg/kg p.o.). The onset was rapid and could not be reverted by the beta-adrenoceptor blocking agents, indicating that the rapid heart rate was not solely a result of increased sympathetic outflow to the heart [55]. Using radiotelemetry devices diazepam (6 mg/kg i.p.)…”

Section: Cardiovascular Effects Of Positive Allosteric Modulators mentioning

confidence: 99%

Central and Peripheral GABA_AReceptor Regulation of the Heart Rate Depends on the Conscious State of the Animal

Bentzen

Grunnet

2011

Advances in Pharmacological Sciences

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Intuitively one might expect that activation of GABAergic inhibitory neurons results in bradycardia. In conscious animals the opposite effect is however observed. GABAergic neurons in nucleus ambiguus hold the ability to control the activity of the parasympathetic vagus nerve that innervates the heart. Upon GABA activation the vagus nerve will be inhibited leaving less parasympathetic impact on the heart. The picture is however blurred in the presence of anaesthesia where both the concentration and type of anaesthetics can result in different effects on the cardiovascular system. This paper reviews cardiovascular outcomes of GABA activation and includes own experiments on anaesthetized animals and isolated hearts. In conclusion, the impact of changes in GABAergic input is very difficult to predict in these settings, emphasizing the need for experiments performed in conscious animals when aiming at determining the cardiovascular effects of compounds acting on GABAergic neurons.

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Analysis of cradiac chromotropic responses to diazepam and bromazepam in conscious trained dogs

Cited by 20 publications

References 11 publications

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

Effects of triazolam on heart rate level and on phasic cardiac response to noise during sleep

Central and Peripheral GABA_AReceptor Regulation of the Heart Rate Depends on the Conscious State of the Animal

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Analysis of cradiac chromotropic responses to diazepam and bromazepam in conscious trained dogs

Cited by 20 publications

References 11 publications

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

Effect of Diazepam on 24-Hour Blood Pressure and Heart Rate in Healthy Young Volunteers

Effects of triazolam on heart rate level and on phasic cardiac response to noise during sleep

Central and Peripheral GABAAReceptor Regulation of the Heart Rate Depends on the Conscious State of the Animal

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Product

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Central and Peripheral GABA_AReceptor Regulation of the Heart Rate Depends on the Conscious State of the Animal