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Biomedical subjects

N E Farber

Publications and source records attributed to N E Farber.

At least 19 recordsLinked to original sources
PubMed2000

Neuronal nitric oxide synthase mediates halothane-induced cerebral microvascular dilation.

BACKGROUND: The causes of volatile anesthetic-induced cerebral vasodilation include direct effects on smooth muscle and indirect effects via changes in metabolic rate and release of mediators from vascular endothelium and brain parenchyma. The role of nitric oxide and the relative importance of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) are unclear. METHODS: Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arteriolar diameters were measured using computerized videomicrometry. Vessels were preconstricted with prostaglandin F2alpha (PGF2alpha; halothane group) or pretreated with 7-nitroindazole sodium (7-NINA, specific nNOS inhibitor, 7-NINA + halothane group) or N-nitro-L-arginine methylester (L-NAME; nonselective NOS inhibitor, L-NAME + halothane group) and subsequently given PGF2alpha to achieve the same total preconstriction as in the halothane group. Increasing concentrations of halothane were administered and vasodilation was calculated as a percentage of preconstriction. RESULTS: Halothane caused significant, dose-dependent dilation of hippocampal microvessels (halothane group). Inhibition of nNOS by 7-NINA or nNOS + eNOS by L-NAME similarly attenuated halothane-induced dilation at 0.6, 1.6, and 2.6% halothane. The dilation (mean +/- SEM) at 1.6% halothane was 104 +/- 10%, 65 +/- 6%, and 51 +/- 9% in the halothane, 7-NINA + halothane and L-NAME + halothane groups, respectively. The specificity of 7-NINA was confirmed by showing that acetylcholine-induced dilation was not inhibited by 7-NINA but was converted to constriction by L-NAME. CONCLUSIONS: At clinically relevant concentrations, halothane potently dilates intracerebral arterioles. This dilation is mediated, in part, by neuronally derived nitric oxide. Endothelial NOS does not play a major role in halothane-induced dilation of hippocampal microvessels.

Analysis of Variance↗
PubMed1999

Dexmedetomidine modulates cardiovascular responses to stimulation of central nervous system pressor sites.

UNLABELLED: Halothane attenuates the alterations in arterial pressure (BP) and heart rate (HR) produced by central nervous svstem (CNS) stimulation. We examined the effects of the alpha2-adrenergic agonist dexmedetomidine, with and without halothane, on cardiovascular regulation during CNS pressor site stimulation in chronically instrumented cats. Stimuli trains via bipolar stimulating electrodes in the hypothalamus and reticular formation elicited pressor responses. Dexmedetomidine-induced (15 microg/kg PO) bradycardia was greater in the presence of halothane. CNS stimulation increased BP and HR, which were dose-dependently attenuated by halothane (hypothalamic stimulation 71 +/- 9 mm Hg at control, 25 +/- 5 and 15 +/- 3 mm Hg at 1.0% and 1.5% halothane, respectively). Although dexmedetomidine alone did not alter pressor responses, halothane plus dexmedetomidine attenuated pressor responses in a potentially synergistic fashion (hypothalamic stimulation 67 +/- 8 mm Hg at control, 2 +/- 1 and 1 +/- 0.4 mm Hg at 1.0% and 1.5% halothane, respectively). These results suggest differences in the disruptive effects of CNS-mediated cardiovascular responses by halothane and dexmedetomidine, and that dexmedetomidine has an anesthetic-sparing effect on these CNS-mediated cardiovascular control mechanisms, potentiating the depressant effect of halothane. IMPLICATIONS: A new potential anesthetic adjunct, dexmedetomidine, does not attenuate brain-mediated increases in blood pressure, but the combination of dexmedetomidine and the anesthetic halothane acts to modulate central cardiovascular responses.

Adrenergic alpha-Agonists↗
PubMed1999

Pretreatment with dexmedetomidine: altered indices of anesthetic depth for halothane in the neuraxis of cats.

UNLABELLED: The sedative and anesthetic-sparing ability of the alpha2-adrenergic agonist dexmedetomidine is well documented. In this study, we identified the effects of halothane, with and without dexmedetomidine, on hemodynamic and electroencephalographic (EEG) variables and quantified the concentration of halothane resulting in various anesthetic depth indices mediated through the central nervous system (CNS) in chronically instrumented cats. Halothane was given alone or after dexmedetomidine (15 microg/kg p.o.). In both groups, four indices of anesthetic depth--minimum alveolar anesthetic concentration (MAC; no movement to noxious stimuli), MAC(BAR) (no autonomic response to noxious stimuli), MAC(BS) (EEG burst suppression), and MAC(ISOELECTRIC) (EEG isoelectricity)--were determined. Halothane decreased arterial blood pressure, heart rate, and higher frequency components of the EEG before the onset of burst suppression and isoelectricity. Dexmedetomidine pretreatment augmented the actions of halothane on arterial pressure, heart rate, and the EEG. Dexmedetomidine reduced the halothane concentrations resulting in MAC (from 1.22% +/- 0.06% to 0.89% +/- 0.08%) and MAC(BAR) (from 1.81% +/- 0.05% to 1.1% +/- 0.10%), but not those resulting in MAC(BS) (3.01% +/- 0.17% vs 3.14% +/- 0.10%) or MAC(ISOELECTRIC) (4.39% +/- 0.26% vs 4.65% +/- 0.12%). These results suggest that dexmedetomidine does not alter various CNS-mediated indices of anesthetic action to equivalent degrees and that there are dissimilar degrees of an anesthetic-sparing action at different levels of the neuraxis. IMPLICATIONS: The anesthetic adjuvant dexmedetomidine seems to differentially alter central nervous system-mediated indices of anesthetic action. Lower brainstem or spinal determinants of anesthetic depth (movement and hemodynamic responses) are more attenuated than those of higher brain functions, such as the electroencephalogram.

Adrenergic alpha-Agonists↗
PubMed1999

Effects of hypoxia-reoxygenation on microvascular endothelial function in the rat hippocampal slice.

BACKGROUND: Cerebral ischemia and hypoxia may cause injury to both neuronal and vascular tissue. The direct effects of hypoxia on endothelial function in intraparenchymal cerebral arterioles are unknown. Using a modification of the rat brain slice preparation, allowing continuous imaging of these previously inaccessible vessels, microvessel dilation was evaluated before and after a brief hypoxic episode. METHODS: Rat brain slices were superfused with oxygenated artificial cerebrospinal fluid. Hippocampal arterioles were visualized using computerized videomicroscopy, and their diameters (range, 12-27 microm) were measured using image analysis. After preconstriction with prostaglandin F2alpha and controlled pH and carbon dioxide tension, graded concentrations of either acetylcholine (endothelium-dependent vasodilation) or sodium nitroprusside (endothelium-independent vasodilation) were given before and after a 10-min period of hypoxia. RESULTS: Sodium nitroprusside (100 microM) caused similar dilation before and after hypoxia (mean +/- SEM: 9.6 +/- 0.6% vs. 13.0 +/- 0.9%). Acetylcholine (100 microM) caused significantly less dilation (P < 0.05) after hypoxia (mean +/- SEM: 9.3 +/- 1.8% vs. 3.6 +/- 1.2%). The decreased acetylcholine-induced dilation after hypoxia was not reversed by pretreatment with L-arginine (1 mM), the precursor of nitric oxide (mean +/- SEM: 8.8 +/- 1.3% vs. 4.4 +/- 0.7%). CONCLUSIONS: Even brief periods of hypoxia may cause endothelial dysfunction in intraparenchymal cerebral arterioles. This does not seem to be related to a deficiency of the nitric oxide substrate, L-arginine. Endothelial dysfunction and impaired endothelium-dependent dilation of microvessels may decrease oxygen delivery and increase neuronal injury during cerebral hypoxia-reoxygenation.

Acetylcholine↗
PubMed1998

The effects of graded hypoxia on intraparenchymal arterioles in rat brain slices.

Hypoxia-induced changes in intracerebral arterioles, the major determinants of local cerebral oxygen delivery, are not well understood. Hippocampal arteriolar diameters were measured in rat brain slices using computerized videomicroscopy. In group 1 (control), artificial cerebrospinal fluid oxygen tension (PO2) was maintained at 500 mmHg. In groups 2 and 3, PO2 was gradually reduced to anoxia (95% N2/5% CO2). In group 3, prostaglandin F2a alpha was given to approximate physiological myogenic tone. PCO2 and pH were controlled. Graded hypoxia progressively dilated vessels (PO2 300 mmHg = 2.4 +/- 1.2%, 4.2 +/- 1.6%; PO2 90 mmHg = 15.4 +/- 3.0%, 14.5 +/- 1.8%; groups 2 and 3, respectively). The presence of preconstriction did not influence the extent of hypoxia-induced dilation. This vasorelaxation may be important in maintaining cerebral oxygen delivery during microvascular hypoxia.

Animals↗
PubMed1998

A novel alpha 2-adrenoceptor antagonist attenuates the early, but preserves the late cardiovascular effects of intravenous dexmedetomidine in conscious dogs.

OBJECTIVES: To test the hypothesis that L-659,066, a peripherally acting alpha 2-adrenoceptor agonist, will abolish the early pressor response but preserve the late depressor action of intravenous dexmedetomidine in conscious, unsedated dogs. DESIGN: A prospective investigation. SETTING: A laboratory research. PARTICIPANTS: Nine chronically instrumented dogs. INTERVENTIONS: Dogs received dexmedetomidine, 5 micrograms/kg intravenously, in the presence or absence of L-659,066, 0.1, 0.2, or 0.4 mg/kg intravenously, pretreatment in a random fashion determined with a Latin square design on different experimental days. MEASUREMENTS AND MAIN RESULTS: Systemic and coronary hemodynamics were assessed under control conditions, 30 minutes after administration of L-659,066 and 5 and 60 minutes after intravenous administration of dexmedetomidine. Dexmedetomidine alone acutely increased mean arterial pressure (106 +/- 3 to 175 +/- 4 mmHg; p < 0.05), left ventricular (LV) systolic and end-diastolic pressures, systemic vascular resistance (3,400 +/- 350 to 13,360 +/- 2,290 dyne.s.cm-5; p < 0.05), and coronary vascular resistance (2.69 +/- 0.19 to 4.18 +/- 0.43 mmHg.Hz-1.10(-2); p < 0.05) and decreased LV +dP/dtmax and cardiac output (2.6 +/- 0.3 to 1.3 +/- 0.2 L/min; p < 0.05). Dexmedetomidine alone decreased heart rate, mean arterial pressure, and LV systolic pressure and caused sustained reductions in +dP/dtmax and cardiac output up to 60 minutes after administration. L-659,066 alone increased heart rate, +dP/dtmax, cardiac output, and coronary blood flow velocity and decreased systemic vascular resistance. Mean arterial and LV pressures and coronary vascular resistance were unchanged. Pretreatment with L-659,066 abolished the acute dexmedetomidine-induced increases in mean arterial pressure, LV pressures, systemic and coronary vascular resistance and decreases in +dP/dtmax and cardiac output. In contrast, reductions in mean arterial pressure and LV systolic pressure observed 60 minutes after administration of dexmedetomidine were preserved in dogs receiving L-659,066. Cardiac performance, systemic vascular resistance, and coronary hemodynamics were also maintained to a greater degree 60 minutes after dexmedetomidine administration in the presence of L-659,066. CONCLUSION: L-659,066 prevents the immediate pressor effects of 5 micrograms/kg of intravenous dexmedetomidine but preserves the majority of the late beneficial cardiovascular effects of this selective alpha 2-adrenoceptor agonist in conscious dogs.

Adrenergic alpha-Agonists↗
PubMed1998

In vivo effects of dexmedetomidine on laser-Doppler flow and pial arteriolar diameter.

BACKGROUND: The alpha2-adrenergic agonist dexmedetomidine alters global cerebral blood flow (CBF). However, few studies have investigated the action of dexmedetomidine on the cerebral microcirculation. This investigation examined the effects of dexmedetomidine on (1) regional CBF in the rat cerebral cortex using laser-Doppler flowmetry and (2) on pial arteriolar diameter. METHODS: Halothane-anesthetized rats were fitted with instruments to measure CBF as determined by laser-Doppler flow (CBFldf) or to measure pial arteriolar diameter by preparing a cranial hollow deepened until a translucent plate of skull remained, thereby maintaining the integrity of the cranial vault. In both groups, 20 microg/kg dexmedetomidine was infused intravenously. Thirty minutes later, the mean arterial pressure was restored to control values with an infusion of phenylephrine (0.5 to 5 microg/kg/min). RESULTS: Administration of dexmedetomidine was associated with decreases in end-tidal and arterial carbon dioxide. The CBFldf and pial arteriolar diameter were measured during normocapnia (controlled carbon dioxide) and during dexmedetomidine-induced hypocapnia. Intravenous administration of dexmedetomidine significantly decreased systemic arterial pressure concurrent with a decrease in CBFldf (22% in normocapnic animals, 36% in hypocapnic animals). Restoration of mean arterial pressure increased CBFldf in normocapnic but not in hypocapnic animals. Similarly, dexmedetomidine significantly reduced pial vessel diameter in both normocapnic (9%) and hypocapnic animals (17%). However, vessel diameters remained decreased in the normocapnic and hypocapnic animals after the mean arterial pressure was restored. CONCLUSIONS: These results suggest a modulation of cerebral vascular autoregulation by dexmedetomidine which may be mediated, in part, by alterations in carbon dioxide. Dexmedetomidine may have a direct action on the cerebral vessels to reduce the CBF during normo- or hypocapnia. The differences between CBFldf and pial arteriole responses to restoration of mean arterial pressure may reflect the difference in measurement techniques because laser-Doppler measurements reflect the net effect of several arterial segments on microvascular perfusion, whereas diameter measurements specifically examined individual pial arterioles, suggesting that dexmedetomidine vasoconstriction in the cerebral vasculature may be differentially and regionally mediated.

Adrenergic alpha-Agonists↗
PubMed1997

Dexmedetomidine and halothane produce similar alterations in electroencephalographic and electromyographic activity in cats.

Dexmedetomidine, an alpha2-adrenergic agonist, produces sedation and reduces volatile anesthetic requirements. This investigation compared the actions of dexmedetomidine and halothane on the processed EEG and on the electromyogram (EMG) which has not been previously described. Chronically instrumented cats were prepared with arterial and venous cannulae, quadriceps EMG electrodes and EEG electrodes in the lateral geniculate nucleus and over the frontal and occipital cortices. Hemodynamics, EEG and EMG were recorded in the conscious state and after randomly administered halothane or intravenous dexmedetomidine (on separate days). Blink and tail-clamp responses also assessed level of consciousness. Halothane resulted in unconsciousness and a lack of response to tail clamping, while dexmedetomidine produced profound sedation, with preservation of tail-clamp responses. Both agents similarly decreased (P < 0.05) the median power frequency from 9.5 +/- 0.9 to 5.7 +/- 0.4 Hz (2% halothane) and from 9.6 +/- 0.7 to 5.9 +/- 0.8 Hz (20 microg/kg dexmedetomidine), and 95% power frequency from 23.0 +/- 0.2 to 18.2 +/- 0.6 Hz (2% halothane) and from 23.0 +/- 0.2 to 19.1 +/- 0.8 Hz (20 microg/kg dexmedetomidine). Both agents increased the total spectral power and delta band power of the EEG and reduced integrated EMG activity. Halothane and dexmedetomidine produced differing effects on level of consciousness as assessed by response to tail clamping. The results suggest that conventional processing of EEG and EMG parameters are inadequate to assess anesthetic depth in the presence of alpha2-adrenergic agonists.

Adrenergic alpha-Agonists↗
PubMed1997

The effects of hyper- and hypocarbia on intraparenchymal arterioles in rat brain slices.

This investigation examined the direct effects of hyper- and hypocarbia on intracerebral resistance vessels within an intact neuronal synctium. Hippocampal rat brain slices were superfused with artificial cerebrospinal fluid (aCSF). Arterioles were located and diameter changes in response to alterations in aCSF carbon dioxide tension (pCO2) were monitored with videomicroscopy. Microvessels dose dependently dilated and constricted during hyper- and hypocarbia, respectively. A two-fold rise in pCO2 produced a 20% increase in diameter, while a 47% decrease in pCO2 vasoconstricted microvessels by 11%. This is the first model allowing the investigation of the direct actions of physiologic mediators on discrete intracerebral resistance vessels in situ. The results suggest that intracerebral microvessels significantly respond to changes in pCO2 and may be intimately involved in alterations in cerebral vascular resistance.

Animals↗
PubMed1997

Halothane-induced dilatation of intraparenchymal arterioles in rat brain slices: a comparison to sodium nitroprusside.

BACKGROUND: Halothane is a potent dilator of cerebral arteries. The predominant site of cerebrovascular resistance is thought to be intracerebral arterioles, and the effects of halothane on these vessels were not previously examined. This study compared the effects of halothane with those of the vasodilator and nitric oxide donor, sodium nitroprusside, on intraparenchymal microvessel responsiveness in a brain slice preparation. METHODS: Anesthetized Sprague-Dawley rats underwent thoracotomy and intracardiac perfusion and then were decapitated. Hippocampal brain slices were prepared and placed in a perfusion/recording chamber and superfused with artificial cerebrospinal fluid. An arteriole was located within the brain parenchyma and its diameter was monitored with videomicroscopy before, during, and after various concentrations of halothane or sodium nitroprusside were equilibrated in the perfusate. All vessels were preconstricted with prostaglandin F2 alpha before halothane or sodium nitroprusside treatment. An observer blinded to treatment analyzed vessel diameter changes with a computerized videomicrometer. RESULTS: Baseline microvessel diameter was 18 +/- 2 microns in the halothane group (n = 14) and 15 +/- 1 microns in the sodium nitroprusside group (n = 15). Prostaglandin F2 alpha (0.5 micron) preconstricted vessels by approximately 15% from resting diameter in both groups. Halothane significantly and dose dependently dilated intracerebral microvessels by 54% +/- 6%, 74% +/- 8%, 108% +/- 13%, and 132% +/- 7% (normalized to the preconstricted diameter) at 0.5%, 1.0%, and 2.5% halothane, respectively. This dilatation corresponds to a decrease in a calculated index of cerebrovascular resistance index of up to 117% +/- 2% at 2.5% halothane. Sodium nitroprusside, in concentrations ranging from 10(-8) to 10(-3)M, also dose dependently dilated these intraparenchymal vessels by 129% +/- 7% at the highest concentration. These alterations in microvessel diameter corresponded to a decrease in the cerebrovascular resistance index of up to 116 +/- 4% for the largest dose. CONCLUSIONS: Halothane produces dose-dependent vasodilatation of intraparenchymal cerebral microvessels, thus predicting marked decreases in cerebrovascular resistance in this in vitro brain slice preparation. The effects of halothane on these cerebral microvessels are similar to those of the potent vasodilator sodium nitroprusside. These findings suggest that direct effects of halathane on cerebral microvessels diameter contribute substantially to alterations in cerebrovascular resistance and flow produced by this agent.

Anesthetics, Inhalation↗
PubMed1997

Region-specific and agent-specific dilation of intracerebral microvessels by volatile anesthetics in rat brain slices.

BACKGROUND: Volatile anesthetics are potent cerebral vasodilators. Although the predominant site of cerebrovascular resistance is attributed to intracerebral arterioles, no studies have compared the actions of volatile anesthetics on intraparenchymal microvessels. The authors compared the effects of halothane and isoflurane on intracerebral arteriolar responsiveness in hippocampal and neocortical microvessels using a brain slice preparation. METHOD: After Institutional Review Board approval, hippocampal or neocortical brain slices were prepared from anesthetized Sprague-Dawley rats and placed in a perfusion-recording chamber, superfused with artificial cerebrospinal fluid. Arteriolar diameters were monitored with videomicroscopy before, during, and after halothane or isoflurane were equilibrated in the perfusate. PGF2alpha preconstricted vessels before anesthetic administration. A blinded observer using a computerized videomicrometer analyzed diameter changes. RESULTS: Baseline microvessel diameter and the degree of preconstriction were not different between groups. In the hippocampus, the volatile agents produced similar, concentration-dependent dilation (expressed as percent of preconstricted control +/- SEM) of 68 +/- 6% and 79 +/- 9% (1 MAC) and 120 +/- 3% and 109 +/- 5% (2 MAC) (P < 0.05) during halothane and isoflurane, respectively. In the cerebral cortex, isoflurane caused significantly less vasodilation than did similar MAC levels of halothane (84 +/- 9% vs. 42 +/- 5% dilation at 1 MAC; 121 +/- 4% vs. 83 +/- 5% dilation at 2 MAC halothane vs. isoflurane, respectively). CONCLUSION: Halothane and isoflurane differentially produce dose-dependent dilation of intraparenchymal cerebral microvessels. These findings suggest that local effects of the volatile anesthetics on intracerebral microvessel diameter contribute significantly to alterations in cerebrovascular resistance and support previously described heterogeneous actions on cerebral blood flow produced by these agents.

Anesthetics, Inhalation↗
PubMed1997

Massive blood loss during tonsillectomy in a child with congenital venous malformation.

Tonsillectomy and adenoidectomy have become frequently performed outpatient procedures and are generally considered to have a low morbidity profile. Postoperative haemorrhage remains a rare but important complication, while intraoperative uncontrollable bleeding is extremely uncommon. A child with congenital vascular malformation of the lip and oropharynx undergoing tonsillectomy experienced massive blood loss, subsequent resuscitation and significant perioperative morbidity including a prolonged intensive care unit stay. Preoperative/preanaesthetic nasopharyngoscopic exam and magnetic resonance imaging did not reveal vascular prominence of the tonsils. Preoperative consideration of angiography or magnetic resonance angiography may be prudent to avoid this potentially fatal complication.

Adenoidectomy↗
PubMed1996

Electrosurgery-induced ventricular fibrillation during pacemaker replacement--a unique mechanism.

Arrhythmias and pacemaker malfunction are known to occur from the use of an electrosurgical device. The present case report describes a patient with sick sinus syndrome who experienced ventricular fibrillation while undergoing surgery. During replacement of his non-functioning cardiac pacemaker under general anesthesia, electrosurgery was used to ensure hemostasis. Electric current may have stimulated myocardial leads present in the surrounding tissue, leading to ventricular fibrillation. The patient was resuscitated from the episode without any residual sequelae. Microshock and possible mechanisms that can lead to ventricular arrhythmias in patients with pacemakers during electrosurgery are discussed.

Adult↗
PubMed1996

Desflurane attenuates the somatosympathetic reflex in rats.

Arterial blood pressure and heart rate changes after afferent somatic sensory nerve stimulation are termed the "somatosympathetic reflex" (SSR). Inhibition of the SSR may partially represent an antinociceptive action. This investigation examined the actions of the volatile anesthetic, desflurane, on the SSR evoked by peripheral nerve stimulation. Rats anesthetized with alpha-chloralose (50 mg/kg) and urethane (500 mg/kg) were mechanically ventilated and cannulated with arterial and venous catheters for monitoring arterial pressure and for fluid administration, respectively. The sciatic (n = 7) or tibial (n = 6) nerves were isolated and stimulated at one, two, and four times the voltage threshold required to elicit a change in systemic hemodynamics. These cardiovascular responses were recorded before, during, and after varying concentrations of desflurane, 1.8% (0.25 minimum alveolar anesthetic concentration [MAC]), 3.6% (0.5 MAC), 7.2% (1.0 MAC), and 10.8% (1.5 MAC). Desflurane decreased arterial pressure at 1.0 and 1.5 MAC and heart rate (at more than 0.5 MAC) compared to baseline levels. Tibial nerve stimulation decreased mean arterial pressure (MAP) with no consistent changes in heart rate. Desflurane significantly attenuated this depressor response to tibial nerve stimulation (MAP decrease: control; -20 +/- 2 mm Hg versus 1.0 MAC desflurane; -6 +/- 4 mm Hg). The increases in MAP after sciatic nerve stimulation were also significantly inhibited by increasing concentrations of desflurane. At more than 0.5 MAC desflurane, the pressor response to sciatic nerve stimulation was significantly converted to a depressor response in four of seven rats (MAP: control; increase 24 +/- 2 mm Hg versus 1.0 MAC desflurane; decrease -2 +/- 4 mm Hg). Sciatic nerve stimulation also elicited increases in heart rate which were significantly attenuated by desflurane (control; 37 +/- 6 bpm versus 1.5 MAC desflurane; 0 +/- 2 bpm). These findings demonstrate that desflurane produces dose-dependent cardiovascular depression in rats and, despite previous reports of sympathoexcitation, desflurane significantly attenuated both excitatory and inhibitory types of SSR. The results of this study also support a potential antinociceptive action for this anesthetic.

Anesthetics, Inhalation↗
PubMed1995

The effects of halothane on cardiovascular responses in the neuraxis of cats. Influence of background anesthetic state.

BACKGROUND: This study examined the effects of halothane on arterial pressure after central nervous system (CNS) pressor site stimulation in anesthetized cats, cats rendered unconscious by midcollicular transection, and conscious cats. METHODS: Two anesthetized groups and two nonanesthetized groups were used. Cats were anesthetized with either alpha-chloralose and urethane or pentobarbital. Nonanesthetized groups were cats with midcollicular transections or conscious cats with chronically implanted electrodes. Stimulating electrodes were placed into vasomotor areas of the hypothalamus (HYP), reticular formation (RF), and medulla, and arterial pressure responses to increasing stimulus currents were examined during different halothane concentrations. Two groups of cats were also anesthetized with either pentobarbital or urethane and underwent bilateral carotid artery occlusion. RESULTS: Stimulation at each CNS site produced increases in arterial pressure and heart rate. Halothane attenuated pressor responses evoked by stimulation of all loci in all groups of cats. The inhibition by halothane on these cardiovascular responses was greatest at HYP and RF sites, while the medulla was more resistant to the effects of halothane in the anesthetized animals. Midcollicular transection decreased this medullary resistance. The inhibition of pressor responses by halothane was also greater in pentobarbital-than chloralose urethane-anesthetized animals. In contrast, pressor responses elicited by bilateral carotid occlusion were attenuated by halothane similarly in both anesthetic groups. Reticular formation stimulation in conscious animals resulted in "altering responses" in addition to pressor effects, both of which were attenuated by halothane. CONCLUSIONS: Modulation of CNS cardiovascular control centers contribute to halothane-induced hemodynamic alterations. Baseline anesthesia, CNS stimulation site, and the suprabulbar system influence the effects of halothane.

Anesthesia↗
PubMed1995

Halothane modulates thermosensitive hypothalamic neurons in rat brain slices.

BACKGROUND: In vivo, halothane alters spontaneous firing in and thermosensitivity of neurons in the preoptic region of the anterior hypothalamus. To better understand the mechanisms by which halothane specifically disrupts normal thermoregulation, this investigation examined the effects of halothane on thermosensitive preoptic region neurons in isolated hypothalamic tissue slices. METHODS: Brain slices were obtained and prepared from Sprague-Dawley rats. Preoptic region neurons were characterized by extracellular recording of spontaneous firing rates and thermosensitivity to localized heating and cooling, before, during, and after halothane equilibrated in the perfusate and carrier gas. RESULTS: One hundred sixteen neurons were characterized by their thermosensitivity as: 29% warm-sensitive (> 0.8 spikes.s-1.degrees C-1); 14% cold-sensitive (< 0.6 spikes.s-1.degrees C-1); and 57% temperature-insensitive. Halothane significantly reduced the spontaneous firing rates to 64% of control and the thermosensitivity to 55% of control for warm-sensitive neurons at 1% halothane. Halothane significantly reduced the spontaneous firing rate of cold-sensitive neurons to 24 and 40% of control, and the thermosensitivity to 61 and 36% of control at 0.5, and 1% halothane, respectively. Spontaneous firing rates and thermosensitivity returned toward control values in warm-sensitive neurons (92 and 122% of control, respectively) after discontinuation of halothane, which did not occur in cold-sensitive neurons (49 and 36% of control, respectively). Halothane did not alter the thermosensitive temperature range or the set point temperature at which neurons became most thermosensitive. Halothane also did not affect the firing rates of temperature-insensitive neurons. CONCLUSIONS: Halothane alters the firing rate and thermosensitivity of individual temperature-sensitive neurons in in vitro slices of the preoptic region of the anterior hypothalamus in the absence of afferent modulation. This disruption may result in an imprecision of thermoregulatory responses locally within the preoptic region, to thermal challenges and represents a potential mechanism by which halothane widens the thermoregulatory threshold range.

Action Potentials↗