Effects of Isoflurane on the Baroreceptor Reflex

Seagard, J. L.; Elegbe, E. O.; Hopp, Francis A.; Bošnjak, Željko J.; Colditz, Juliane; Kalbfleisch, John H.; Kampine, John P.

doi:10.1097/00000542-198312000-00005

Cited by 135 publications

(60 citation statements)

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“…Approximately 10-fold higher concentrations were required for propofol to induce a tonic GABAergic current. Our NTS data suggest that the sensitivity of phasic GABA A receptors to propofol in this adult tissue corresponds to estimated therapeutic concentrations (Rudolph & Antkowiak, 2004;Urban et al, 2006;Franks, 2006) and these mechanisms may well contribute to the autonomic dysregulation observed in patients that includes baroreflex depression and sympathoinhibition (Ebert et al, 1992;Ebert, 2005) as in animal models (Seagard et al, 1983;Lee et al, 2002).…”

Section: Discussionmentioning

confidence: 55%

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

et al. 2008

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The anesthetic propofol is thought to induce rapid hypnotic sedation by facilitating a GABAergic tonic current in forebrain neurons. The depression of cardiovascular and respiratory regulation often observed during propofol suggests potential additional actions within the brainstem. Here we determined the impacts of propofol on both GABAergic and glutamatergic synaptic mechanisms in a class of solitary tract nucleus (NTS) neurons common to brainstem reflex pathways. In horizontal brainstem slices, we recorded from NTS neurons directly activated by solitary tract (ST) axons. We identified these second-order NTS neurons by time-invariant ("jitter" <200 µs), "all-or-none" glutamatergic excitatory postsynaptic currents (EPSCs) in response to shocks to the ST. In order to assess propofol actions, we measured ST-evoked, spontaneous and miniature EPSCs and inhibitory postsynaptic currents (IPSCs) during propofol exposure. Propofol prolonged miniature IPSC decay time constants by 50% above control at 1.8 µM. Low concentrations of gabazine (SR-95531) blocked phasic GABA currents. At higher concentrations, propofol (30 µM) induced a gabazine-insensitive tonic current that was blocked by picrotoxin or bicuculline. In contrast, total propofol concentrations up to 30 µM had no effect on EPSCs. Thus, propofol enhanced phasic GABA events in NTS at lower concentrations than tonic current induction, opposite to the relative sensitivity observed in forebrain regions. These data suggest that therapeutic levels of propofol facilitate phasic (synaptic) inhibitory transmission in second order NTS neurons which likely inhibits autonomic reflex pathways during anesthesia.

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Section: Discussionmentioning

confidence: 55%

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

et al. 2008

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“…How ever, the cumulative values of integral renal sympathetic activity were unaltered during isoflurane inhalation. Isoflurane itself does not inhibit baroreceptor reflex at a concentra tion o f< 1.0 MAC [23], while it depresses the central respiratory neural activity [24], There fore, it seems likely that ongoing tonic dis charge was increased secondary to hypoten sion through baroreceptor reflex and the res piration-related phasic activity was decreased through a direct central effect of isoflurane, resulting in seemingly no change in the accu mulated integrals of the renal sympathetic nerve activity.…”

Section: Influence On Renal Sympathetic Nerve Activitymentioning

confidence: 99%

Effects of Isoflurane on Brain Stem Blood Flow and Renal Sympathetic Nerve Activity during Induced Hypotension

Kiriyama

Haji²,

Masuda³

et al. 1997

Pharmacology

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Effects of isoflurane on arterial blood pressure, regional blood flow in the brain stem, and renal sympathetic nerve activity were compared with those during vasodilator-induced hypotension using decerebrate unanesthetized cats. Either prostaglandin E₁ (PGE₁) or trinitroglycerin (TNG) was used to decrease the mean arterial pressure 30% below the control level. The effects of isoflurane (0.5 MAC for 15 min) were examined in the following three conditions: (1) during PGE₁-induced hypotension; (2) during TNG-induced hypotension, and (3) without either vasodilator. Isoflurane decreased the brain stem blood flow in parallel with a systemic blood pressure fall. Electrical activity of the renal sympathetic nerve consisted of a high-amplitude phasic and a low-amplitude tonic discharge. Isoflurane decreased the phasic activity and increased the tonic activity. Although the two vasodilators had a similar effect on systemic blood pressure and renal sympathetic discharge, TNG decreased the brain stem blood flow to a lesser extent than PGE₁. However, the effects of isoflurane on all parameters were statistically identical in the three conditions not treated and pretreated with either vasodilator. Also, the blood concentrations of isoflurane did not differ among the three conditions. The present study demonstrates that isoflurane produces similar effects on systemic blood pressure, regional cerebral blood flow and sympathetic efferent discharge during vasodilator-induced hypotension and without any vasodilator.

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“…Arterial BP was measured via a catheter in the left femoral artery connected to a Statham pressure transducer (Gould, Cleveland, OH) and a polygraph (model 7D; Grass, Quincy, MA). To evoke baroreceptor activity, an isolated carotid sinus preparation was prepared as previously described (29). Briefly, the left carotid sinus was vascularly isolated to permit either a flowthrough pulsatile perfusion of the sinus region at constant mean conditioning pressures or a ramp increase in carotid sinus pressure (CSP) (1-2 mmHg/s).…”

Section: General Proceduresmentioning

confidence: 99%

Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs

Rademacher¹,

Patel²,

Hopp

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Baroreceptor afferent fibers synapse in the nucleus tractus solitarius (NTS) of the medulla. Neuronal cannabinoid (CB)1 receptors are expressed in the NTS and central administration of CB1 receptor agonists affect blood pressure (BP) and heart rate. In addition, there is evidence that endocannabinoids are produced in the brain stem. This study examined whether changes in CB1 receptor activity in the NTS modulated the baroreceptor reflex, contributing to changes seen in BP and heart rate. Baroreflexes were evoked in anesthetized dogs by pressure ramp stimulations of the isolated carotid sinus before and after microinjection of CB1 receptor agonist WIN-55212-2 (1.25-1.50 pmol) or antagonist SR-141716 (2.5-3.0 pmol) into cardiovascular regions of the NTS. Microinjection of the SR-141716 did not affect baseline BP or baroreflex sensitivity. However, SR-141716 significantly prolonged the time needed to return to the baseline level of BP after the pressure ramp. Microinjection of WIN-55212-2 had no effect on the baroreflex. These data suggest that endocannabinoids can modulate the excitability of NTS neurons involved in the baroreceptor reflex, leading to modulation of baroreflex regulation. endocannabinoids; sympathetic outflow; glutamate; SR-141716; WIN-55212-2 IT IS KNOWN THAT THE CANNABINOIDS (CBs) produce cardiovascular effects in vivo. For example, in anesthetized rats and dogs, ⌬ 9 -tetrahydrocannabinol (⌬ 9 -THC) produces a transient pressor response followed by longlasting hypotension and bradycardia (12,16,39). The hypotensive effect of ⌬ 9 -THC is mimicked by various CBs with a rank order of potency that strongly correlates with the affinity of these CBs for the neuronal CB 1 receptor (15). The administration of the endocannabinoid, N-arachidonylethanolamine (AEA; anandamide), produces a brief pressor response, followed by a prolonged decrease in blood pressure (BP) (37). The AEA-induced depressor response is inhibited by coadministration of the CB 1 receptor antagonist, SR-141716 (37), and is absent in CB 1 null mice (13).The hypothesis was made decades ago that the hypotensive and bradycardiac effects of the CBs resulted from an inhibition of sympathetic outflow (10, 40). For instance, the hypotensive effect of the synthetic CB, 1-hydroxy-3(1,2-dimethylheptyl)-6,6,9-trimethyl-7,8,9, 10-tetrahydro-6-dibenzopyran (DMHP), was lost with spinal cord transections of the first cervical vertebra. Additionally, the administration of a low dose of DMHP to dogs resulted in a loss of the pressor reflex induced by common carotid artery occlusion. Because the pressor response to epinephrine was preserved in these animals, it was concluded that DMHP interrupted sympathetic innervation of blood vessels (10). Other researchers (40) arrived at the same conclusion and suggested that the site of CB action was at CNS cardioregulatory centers. In contrast, recent animal studies using AEA and the CB 1 receptor agonist WIN-55212-2 suggest that CBs also act at CNS cardioregulatory centers, and the result of these effects is enhan...

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Effects of Isoflurane on the Baroreceptor Reflex

Cited by 135 publications

References 0 publications

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

Propofol enhances both tonic and phasic inhibitory currents in second-order neurons of the solitary tract nucleus (NTS)

Effects of Isoflurane on Brain Stem Blood Flow and Renal Sympathetic Nerve Activity during Induced Hypotension

Microinjection of a cannabinoid receptor antagonist into the NTS increases baroreflex duration in dogs

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