Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trimethaphan”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMed1980

Blood pressure, not cardiac output, determines blood loss during induced hypotension.

Cardiac output characteristically decreases during trimethaphan infusion but is well maintained or increased during sodium nitroprusside infusion. We postulated that at similar levels of mean arterial pressure, sodium nitroprusside might be associated with greater blood loss than trimethaphan due to the increase in cardiac output. We studied 20 young healthy patients scheduled for bilateral sagittal osteotomies of the mandible. Ten subjects received trimethaphan and 10 subjects received sodium nitroprusside. Using halothane (0.8% to 1%) and nitrous oxide (60%) for maintenance of anesthesia, trimethaphan or sodium nitroprusside was infused to maintain mean arterial pressure between 55 to 60 torr. Cardiac output was measured in five subjects in each group. Heart rate and cardiac output increased significantly and total peripheral resistance decreased significantly during sodium nitroprusside infusion when compared to trimethaphan infusion. There were no significant differences in duration of hypotension or in blood loss. We conclude that operative blood loss during induced hypotension is determined by mean arterial pressure, not cardiac output.

Adolescent↗
PubMed1995

The inhibitory effects of nicotinic antagonists on currents elicited by GABA in rat hippocampal neurons.

The nicotinic antagonists d-tubocurarine and trimethaphan camsylate competitively inhibit GABA-induced currents. Hexamethonium, mecamylamine and dihydro-beta-erythroidine, other nicotinic antagonists, do not affect GABA-elicited currents. The trimethaphan effect is completely reversed by a putative convulsant receptor antagonist, alpha-isopropyl-alpha-methyl-gamma-butyrolactone, which implies that the trimethaphan binding site may be closely associated with the convulsant site. However, nicotine was ineffective in competing for either the d-tubocurarine or trimethaphan effect at the GABAA receptor. From these observations, we propose that the nicotinic and GABAA receptor ionophore complexes share similar configurational patterns that accommodate some of the same molecules. Possible mechanisms for the trimethaphan and d-tubocurarine blockades are discussed.

Animals↗
PubMed2000

A new sign of sympathetic neurocirculatory failure: premature ventricular contraction as a "one-beat Valsalva maneuver".

Sympathetic neurocirculatory failure (SNF) features orthostatic hypotension and abnormal beat-to-beat blood pressure (BP) responses to the Valsalva maneuver. This article describes a new sign of SNF, based on changes in BP after premature ventricular contractions (PVCs). Records of supine beat-to-beat BP at rest were reviewed from 22 patients with SNF and 52 control subjects. Records were also taken during intravenous infusion of the ganglion blocker trimethaphan from 38 control subjects. In all 10 control subjects who had PVCs, after the postextrasystolic beat, mean arterial pressure increased progressively to levels higher than before the PVC, peaking at about the eighth beat. In contrast, in all 13 patients with SNF who had PVCs, after the postextrasystolic beat, BP decreased to less than baseline and then increased gradually back to baseline. In all 3 control subjects who had at least one PVC before trimethaphan infusion and another during trimethaphan infusion, the post-PVC pressure pattern during trimethaphan infusion resembled that in SNF patients. Because of a brief increase in sympathetic cardiovascular outflows, after a PVC, BP increases progressively to greater than pre-PVC values, mimicking the pressure overshoot after release of the Valsalva maneuver. Just as the absence of the overshoot of BP after release of the Valsalva maneuver supports a diagnosis of SNF, so does the absence of the overshoot after a PVC.

Blood Pressure↗
PubMed1996

Use of ganglionic blockers to assess neurogenic pressor activity in conscious rats.

The present study was conducted to develop a standardized ganglionic blockade protocol to assess neurogenic pressor activity in conscious rats. Rats were instrumented with arterial and venous catheters for measurement of arterial pressure and heart rate and for administration of three different ganglionic blockers (trimethaphan, hexamethonium, and chlorisondamine). To investigate the role of the pressor hormones angiotensin II (AII) and arginine vasopressin (AVP) in modulating the cardiovascular responses to ganglionic blockade, we also administered ganglionic blockers to rats pretreated with AVP and AII receptor antagonists. The peak depressor responses to trimethaphan (20 mg/kg; -45 +/- 2 mm Hg), hexamethonium (20 mg/kg; -44 +/- 2 mm Hg), and chlorisondamine (2.5 mg/kg; -47 +/- 3 mm Hg) were not different from each other. With trimethaphan, there was a significantly enhanced peak depressor response after blockade of AT1/V1 receptors (-45 +/- 2 vs -59 +/- 2 mm Hg). No significant differences were observed for hexamethonium or chlorisondamine after hormonal blockade (-44 +/- 2 vs. -46 +/- 3 and -47 +/- 3 vs -48 +/- 4 mm Hg, respectively). These observations suggest that, for hexamethonium and chlorisondamine, the peak depressor response to ganglionic blockade is a consistent measure of neurogenic pressor activity in the conscious rat. This response is not influenced by circulating AII or AVP. On the other hand, trimethaphan should be used carefully due to its complex interactions with other systems, particularly under conditions in which AVP or AII may be altered.

Analysis of Variance↗
PubMed1999

Sympathetic ganglionic blockade masks beneficial effect of isoflurane on histologic outcome from near-complete forebrain ischemia in the rat.

BACKGROUND: Isoflurane-anesthetized rats have better outcome from global cerebral ischemia than rats anesthetized with fentanyl and nitrous oxide. The authors wanted to determine whether circulating catecholamine concentrations depend on the anesthetic agent and whether sympathetic ganglionic blockade affects anesthetic-mediated differences in outcome from near-complete forebrain ischemia. METHODS: For two different experiments, normothermic Sprague-Dawley rats that had fasted were assigned to one of four groups and subjected to 10 min of 30 mm Hg mean arterial pressure and bilateral carotid occlusion. Rats were anesthetized with 1.4% isoflurane or fentanyl (25 microg x kg(-1) x h(-1)) and 70% nitrous oxide, with or without preischemic trimethaphan (2.5 mg given intravenously). In experiment 1, arterial plasma catecholamine concentrations were measured before, at 2 and 8 min during, and after ischemia (n = 5-8). In experiment 2, animals (n = 15) underwent histologic analysis 5 days after ischemia. RESULTS: In experiment 1, intraischemic increases in plasma norepinephrine and epinephrine levels were 28 and 12 times greater in the fentanyl-nitrous oxide group than in the isoflurane group (P<0.01). Trimethaphan blocked all changes in plasma catecholamine concentrations (P<0.02). In experiment 2, isoflurane reduced the mean +/- SD percentage of dead hippocampal CA1 neurons compared with fentanyl-nitrous oxide (43+/-22% vs. 87+/-10%; P<0.001). Trimethaphan abolished the beneficial effects of isoflurane (91+/-6%; P<0.001). Similar observations were made in the cortex. CONCLUSIONS: Isoflurane attenuated the peripheral sympathetic response to ischemia and improved histologic outcome compared with fentanyl and nitrous oxide. This outcome benefit was reversed by sympathetic ganglionic blockade. The beneficial effects of isoflurane may result from a neuroprotective influence of an intermediate sympathetic response that is abolished by trimethaphan.

Anesthetics, Inhalation↗
PubMed2000

Periischemic cerebral blood flow (CBF) does not explain beneficial effects of isoflurane on outcome from near-complete forebrain ischemia in rats.

BACKGROUND: Isoflurane improves outcome from near-complete forebrain ischemia in rats compared with fentanyl-nitrous oxide (N2O). Sympathetic ganglionic blockade with trimethaphan abolishes this beneficial effect. To evaluate whether anesthesia-related differences in cerebral blood flow (CBF) may explain these findings, this study compared regional CBF before, during, and after near-complete forebrain ischemia in rats anesthetized with either isoflurane (with and without trimethaphan) or fentanyl-nitrous oxide. METHODS: Fasted, normothermic isoflurane anesthetized Sprague-Dawley rats were prepared for near-complete forebrain ischemia (10 min of bilateral carotid occlusion and mean arterial pressure = 30 mmHg). After surgery, rats were anesthetized with either 1.4% isoflurane (with or without 2.5 mg of trimethaphan intravenously at onset of ischemia) or fentanyl-nitrous oxide (25 microgram. kg-1. h-1. 70% N2O-1). Regional CBF was determined (14C-iodoantipyrine autoradiography) before ischemia, 8 min after onset of ischemia, and 30 min after onset of reperfusion. RESULTS: Regional CBF did not differ significantly among groups at any measurement interval. Ischemia caused a marked flow reduction to 5% or less of baseline (P < 0.001) in selectively vulnerable regions, such as the cortex, caudoputamen and hippocampus, whereas flow in the brain stem and cerebellum was preserved. Reperfusion at 30 min was associated with partial restoration of flow to 35-50% of baseline values in ischemic structures. CONCLUSIONS: The results indicate that improved histologic-behavioral outcome provided by isoflurane anesthesia cannot be explained by differential vasodilative effects of the anesthetic states before, during, or after severe forebrain ischemia. This study also shows severe postischemic delayed hypoperfusion that was not affected by choice of anesthetic or the presence of trimethaphan. Mechanisms other than effects on periischemic CBF must be responsible for beneficial effects of isoflurane in this model.

Anesthetics, Inhalation↗
PubMed1990

Neurophysiological evidence for and characterization of the post-ganglionic innervation of the adrenal gland in the rat.

The aim of this study was to examine and characterize the post-ganglionic innervation of the adrenal gland, using a neurophysiological nerve recording technique. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for post-ganglionic nerve activity, trimethaphan, a ganglionic blocker, was given intravenously. About 60% of the adrenal nerve preparations tested responded with a marked decrease in nerve activity (to 52 +/- 11% of pre-trimethaphan activity, P less than 0.01), while other nerves responded with an increase in activity (to 152 +/- 29% of pre-trimethaphan activity, P less than 0.01). Based on these responses, the nerves were considered to contain predominantly post- or preganglionic fibres respectively, and the difference in response to an intravenous injection of trimethaphan between the two groups was significant (P less than 0.01). It was also demonstrated that the post-ganglionic adrenal nerve activity had a greater variability in firing pattern than preganglionic adrenal nerve activity. We also examined whether there was any cardiac rhythmicity in the investigated nerves. There was a weak cardiac rhythmicity in six out of 12 post-ganglionic adrenal nerves, but there was no cardiac rhythmicity in the remaining six post-ganglionic nerves, and we observed no cardiac rhythmicity in preganglionic nerves. In contrast, renal sympathetic nerves showed a profound cardiac rhythmicity. Our results might explain recent histological findings of a direct post-ganglionic innervation of the adrenal cortex. We speculate that this nerve population is involved in steroid synthesis indirectly via regulation of the cortical blood flow or directly via a direct innervation of parenchymal cells in the adrenal cortex.

Adrenal Glands↗
PubMed1998

N(N)-nicotinic blockade as an acute human model of autonomic failure.

Pure autonomic failure has been conceptualized as deficient sympathetic and parasympathetic innervation. Several recent observations in chronic autonomic failure, however, cannot be explained simply by loss of autonomic innervation, at least according to our current understanding. To simulate acute autonomic failure, we blocked N(N)-nicotinic receptors with intravenous trimethaphan (6+/-0.4 mg/min) in 7 healthy subjects (4 men, 3 women, aged 32+/-3 years, 68+/-4 kg, 171+/-5 cm). N(N)-Nicotinic receptor blockade resulted in near-complete interruption of sympathetic and parasympathetic efferents as indicated by a battery of autonomic function tests. With trimethaphan, small postural changes from the horizontal were associated with significant blood pressure changes without compensatory changes in heart rate. Gastrointestinal motility, pupillary function, saliva production, and tearing were profoundly suppressed with trimethaphan. Plasma norepinephrine level decreased from 1.1+/-0.12 nmol/L (180+/-20 pg/mL) at baseline to 0.23+/-0.05 nmol/L (39+/-8 pg/mL) with trimethaphan (P<.001). There was a more than 16-fold increase in plasma vasopressin (P<.01) and no change in plasma renin activity. We conclude that blockade of N(N)-cholinergic receptors is useful to simulate the hemodynamic alterations of acute autonomic failure in humans. The loss of function with acute N(N)-cholinergic blockade is more complete than in most cases of chronic autonomic failure. This difference may be exploited to elucidate the contributions of acute denervation and chronic adaptation to the pathophysiology of autonomic failure. N(N)-Cholinergic blockade may also be applied to study human cardiovascular physiology and pharmacology in the absence of confounding baroreflexes.

Adult↗
PubMed2001

Altered autonomic support of arterial blood pressure with age in healthy men.

BACKGROUND: Primary aging is associated with changes in the autonomic nervous system (ANS), but the functional significance of these changes for systemic circulatory control of arterial blood pressure (BP) is unknown. We tested the hypothesis that ANS support of BP is altered in healthy older humans. METHODS AND RESULTS: A total of 23 young (aged 24+/-1 years; systolic/diastolic BP, 126+/-2/66+/-1 mm Hg) and 16 older (aged 65+/-1 years; systolic/diastolic BP, 125+/-3/62+/-2 mm Hg) healthy men were studied before and during ganglionic blockade (intravenous trimethaphan). The reduction in mean BP (radial artery catheter) with trimethaphan was almost twice as great in the older men (-33+/-2 versus -19+/-2 mm Hg; -40% versus -22% of baseline; P<0.01) due to a lack of increase in heart rate (3+/-2 versus 25+/-2 bpm; P<0.001) and cardiac output (-0.42+/-0.19 versus 1.01+/-0.26 L/min; P<0.001); the decreases in systemic vascular resistance were not different. The absence of tachycardia in the older men was associated with reduced baseline heart rate variability (HRV, P<0.05); the change in heart rate with trimethaphan correlated with the standard deviation of the R-R intervals (HRV(SD R-R interval); r=0.57, P<0.001). Among individual subjects (pooled groups), the reductions in mean BP with trimethaphan were most strongly related to measures of sympathetic activity (r=0.58 to 0.67, P<0.005), change in mean BP with intravenous phenylephrine (r=0.57, P<0.001), and HRV(SD R-R interval) (r=-0.40, P<0.01). CONCLUSIONS: ANS support of BP is altered with age in healthy men due to less cardiac vagal inhibition of heart rate and cardiac output. Basal sympathetic activity and alpha-adrenergic vascular sensitivity are also key physiological correlates of ANS support of BP in healthy men.

Adrenergic alpha-Agonists↗
PubMed2001

The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia.

We studied the mechanisms and physiological relevance of the cephalic insulin response to meal ingestion in 12 healthy women (age 63 +/- 0.4 years; BMI 27.7 +/- 1.7 kg/m2). The ganglionic antagonist, trimethaphan, which impairs neurotransmission across parasympathetic and sympathetic autonomic ganglia, or atropine or saline was given intravenously during the first 15 min after ingestion of a standard meal (350 kcal). During saline infusion, insulin levels increased during the first 10 min after meal ingestion, whereas the first increase in glucose was evident at 15 min. The preabsorptive 10-min insulin response was reduced by 73 +/- 11% by trimethaphan (P = 0.009), accompanied by impaired reduction of glucose levels from 25 to 60 min after meal ingestion (deltaglucose = -1.27 +/- 0.5 [with saline] vs. 0.1 +/- 0.4 mmol/l [with trimethaphan]; P = 0.008). This reduction at 25-60 min in glucose levels correlated significantly to the 10-min insulin response (r = 0.65, P = 0.024). The 10-min insulin response to meal ingestion was also reduced by atropine, but only by 20 +/- 9% (P = 0.045), which was lower than the reduction with trimethaphan (P = 0.004). The preabsorptive insulin response was not accompanied by any increase in circulating levels of gastric inhibitory polypeptide (GIP) or glucagon-like peptide 1 (GLP-1). In conclusion, 1) the early preabsorptive insulin response to meal ingestion in humans can be largely attributed to autonomic activation mediated by noncholinergic and cholinergic mechanisms, 2) this cephalic insulin response is required for a normal postprandial glucose tolerance, and 3) GIP and GLP-1 do not contribute to the preabsorptive cephalic phase insulin response to meal ingestion.

Area Under Curve↗
PubMed1986

Cerebral effects of hypocapnia plus nitroglycerin-induced hypotension in dogs.

This study examined the effect of hypocapnia (PaCO2 20 mm Hg) on cerebral metabolism and the electroencephalogram (EEG) findings in 12 dogs during nitroglycerin (NTG)-induced hypotension. Previous studies suggest that NTG is a more potent cerebral vasodilator than sodium nitroprusside or trimethaphan. It was speculated that combining hypocapnia with NTG-induced hypotension would cause less disturbance of cerebral metabolism and the EEG than the disturbances previously reported when hypocapnia was combined with hypotension induced by sodium nitroprusside or trimethaphan. All 12 dogs were examined at 1) normocapnia with normotension; 2) hypocapnia with normotension; and 3) hypocapnia combined with NTG-induced hypotension to mean arterial blood pressure (MABP) levels of 60, 50, and 40 mm Hg. In six dogs the cerebral metabolic rate of oxygen was determined, and the EEG was evaluated using compressed spectral analysis. Brain tissue metabolites were calculated in the other six dogs. During normotension, hypocapnia caused no deterioration of cerebral metabolism or of the EEG. Hypocapnia combined with NTG-induced hypotension caused a decrease of the power of the alpha and beta 2 spectra of the EEG at MABP's of 60 mm Hg or less. At an MABP of 40 mm Hg, brain tissue phosphocreatine and the cerebral energy charge decreased, while the brain tissue lactate:pyruvate ratio increased. Thirty minutes after restoration of normocapnia with normotension, cerebral metabolites returned to initial values, but the power of the EEG alpha and beta 2 spectra was decreased compared to baseline values. The cerebral metabolic disturbances and EEG alterations seen here with hypocapnia plus NTG-induced hypotension were similar to those previously reported with hypocapnia plus sodium nitroprusside-induced hypotension, and less than those previously reported with hypocapnia plus trimethaphan-induced hypotension. For hyperventilated patients, administration of NTG may be a better hypotensive treatment than trimethaphan, but similar in effect to sodium nitroprusside.

Animals↗
PubMed1995

Dysautoregulation in patients with hypertensive intracerebral hemorrhage. A SPECT study.

In patients with hypertensive intracerebral hemorrhage, changes in regional cerebral blood flow (rCBF) following drug-induced blood pressure reduction were examined by SPECT. METHODS. The subjects were 68 patients with hypertensive intracerebral hemorrhage. The site of cerebral hemorrhage was the thalamus in 28 patients, and the putamen in 40 patients. RCBF was measured by SPECT using the 133Xe inhalation method. To reduce blood pressure, trimethaphan camsilate (an autonomic ganglion blocker) and diltiazem hydrochloride (a calcium antagonist) were used. RESULTS. 1. In the acute period, mean CBF declined as the mean arterial blood pressure declined by more than 20% in both the putaminal and the thalamic hemorrhage group (p < 0.01). 2. During the chronic period, a greater reduction in blood pressure was needed to induce mean CBF reduction. 3. Neither of the two drugs significantly reduced the mean arterial blood pressure, but the group receiving trimethaphan demonstrated a 7.9 approximately 7.5% decreased in CBF, group while the receiving diltiazem showed a 2.2 approximately 2.4% decrease (p < 0.05). CONCLUSIONS. In patients with hypertensive intracerebral hemorrhage, a 20% or more drug-induced decrease in blood pressure resulted in a decrease in mean CBF. During the acute period of intracerebral hemorrhage, blood pressure showed reduced by 20%. Clinically, diltiazem was more effective than trimethaphan.

Adult↗
PubMed1998

Parasympathetic neurons in the cranial medial ventricular fat pad on the dog heart selectively decrease ventricular contractility.

We hypothesized that selective control of ventricular contractility might be mediated by postganglionic parasympathetic neurons in the cranial medial ventricular (CMV) ganglion plexus located in a fat pad at the base of the aorta. Sinus rate, atrioventricular (AV) conduction (ventricular rate during atrial pacing), and left ventricular contractile force (LV dP/dt during right ventricular pacing) were measured in eight chloralose-anesthetized dogs both before and during bilateral cervical vagus stimulation (20-30 V, 0.5 ms pulses, 15-20 Hz). Seven of these dogs were tested under beta-adrenergic blockade (propranolol, 0.8 mg kg(-1) i.v.). Control responses included sinus node bradycardia or arrest during spontaneous rhythm, high grade AV block or complete heart block, and a 30% decrease in contractility from 2118 +/- 186 to 1526 +/- 187 mm Hg s(-1) (P < 0.05). Next, the ganglionic blocker trimethaphan (0.3-1.0 ml of a 50 microg ml(-1) solution) was injected into the CMV fat pad. Then vagal stimulation was repeated, which now produced a relatively small 5% (N.S., P > 0.05) decrease in contractility but still elicited the same degree of sinus bradycardia and AV block (N = 8, P < 0.05). Five dogs were re-tested 3 h after trimethaphan fat pad injection, at which time blockade of vagally-induced negative inotropy was partially reversed, as vagal stimulation decreased LV dP/dt by 19%. The same dose of trimethaphan given either locally into other fat pads (PVFP or IVC-ILA) or systemically (i.v.) had no effect on vagally-induced negative inotropy. Thus, parasympathetic ganglia located in the CMV fat pad mediated a decrease in ventricular contractility during vagal stimulation. Blockade of the CMV fat pad had no effect on vagally-mediated slowing of sinus rate or AV conduction.

Adipose Tissue↗
PubMed1994

Systemic hypertension induced by aortic cross-clamping: detrimental effects of direct smooth muscle relaxation compared with ganglionic blockade.

PURPOSE: Infrarenal aortic cross-clamping performed during vascular reconstructive procedures is often accompanied by systemic supraclamp hypertension. Much of the disease and death that attend aortic cross-clamping centers around hypertension. Many different strategies have been developed to attenuate intraoperative hypertension, and a host of pharmacologic agents are regularly used to lessen the heart-related, cerebral, and systemic effects of clamp-induced hypertension. This study was performed to evaluate two such strategies; the intravenous administration of either trimethaphan camsylate or nitroprusside. METHODS: We used a highly controllable and reproducible model of aortic cross-clamping in which we have previously shown the hypertension associated with clamping to be an active process mediated by means of a reflex arc. Ten dogs, five treated with nitroprusside (NP group) and five treated with trimethaphan camsylate (TC group), underwent 90 minutes of aortic cross-clamping. During this 90-minute period each group received 30 minutes of antihypertensive therapy. RESULTS: Control mean arterial pressure +/- SEM was 80 +/- 5 mm Hg for both groups and increased to 140 +/- 5 mm Hg with clamp application. With antihypertensive treatment the elevation in mean arterial pressure produced by cross-clamping was reduced to preclamp levels in the TC group and only partially (52%) in the NP group, despite very high doses of nitroprusside. Cardiac output (CO) increased in the NP group by 115% and decreased by 36% in the TC group. This increase in CO translates into a large (101%) increase in cardiac minute work for the NP group. CONCLUSIONS: The attenuation of clamp-induced hypertension by nitroprusside is associated with a dramatic increase in CO and cardiac work whereas the use of trimethaphan camsylate is not. The use of this ganglionic blocker may be more appropriate in this setting.

Animals↗
PubMed1982

Effects of hemorrhagic and pharmacologic hypotension on cerebral oxygen utilization and blood flow.

Cerebral oxygen utilization and blood flow were measured by the washout of oxygen-15 isotopes injected into the internal carotid artery in baboons during hypotension produced by acute hemorrhage, trimethaphan, and sodium nitroprusside. Acute hemorrhage, trimethaphan, and sodium nitroprusside lowered the mean arterial blood pressure to 52 per cent, 55 per cent, and 47 per cent, respectively, of control values. There were corresponding decreases in cerebral blood flow to 76 per cent (P less than 0.01), 81 per cent (P less than 0.05), and 79 per cent (P less than 0.01) of control values. When the mean arterial blood pressure was decreased 11 per cent with hemorrhage, auto-regulation of the cerebral vasculature was preserved and cerebral oxygen utilization increased 10 per cent (P less than 0.01). When cerebral autoregulation was lost with acute hemorrhage, cerebral oxygen utilization declined 17 per cent (P less than 0.05). When cerebral autoregulation was lost with pharmacologic hypotension, cerebral oxygen utilization was preserved with trimethaphan and increased 17 per cent (P less than 0.05) with sodium nitroprusside. The increase in cerebral oxygen utilization seen with sodium nitroprusside and hemorrhagic (autoregulation preserved) hypotension may be due to stimulation of the sympathetic nervous system with release of circulating catecholamines. However, the mechanism by which circulating catecholamines mediate an increase in cerebral oxygen metabolism during hypotension is not clear.

Animals↗
PubMed1987

Effect of ganglion blockade on cerebrospinal fluid norepinephrine.

The source of norepinephrine (NE) in CSF has been unclear. It has been suggested that CSF NE indicates central neural noradrenergic tone and is determined differently from plasma NE. If CSF NE depended specifically on NE release in the CNS, then interference with ganglionic neurotransmission would be expected to decrease plasma NE but not CSF NE. Hypotension caused by ganglionic blockade might be expected to increase CSF NE reflexively. We infused the ganglion blocker, trimethaphan, intravenously into anesthetized dogs and measured the effects on mean arterial blood pressure (MAP) and on cisterna magna CSF levels of NE. The results were compared with those obtained on administration of saline, clonidine (2 micrograms/kg), yohimbine (0.25 mg/kg), or nitroprusside and with those obtained when hypotension during ganglion blockade was prevented by concurrent treatment with phenylephrine. Trimethaphan decreased MAP by 40%, arterial NE by 64%, and CSF NE by 61%. Nitroprusside administered intravenously to produce the same 40% depressor response increased arterial NE by 612% and CSF NE by 155%. Prevention of ganglion blockade-induced hypotension using phenylephrine did not prevent the decrease in CSF NE caused by trimethaphan, and when phenylephrine was discontinued, the resulting hypotension was not associated with increases in CSF NE. The similar decreases in plasma NE and CSF NE during ganglionic blockade, and the abolition of reflexive increases in CSF NE during hypotension in ganglion-blocked subjects, cast doubt on the hypothesis that CSF NE indicates central noradrenergic tone and are consistent instead with at least partial derivation of CSF NE from postganglionic sympathetic nerve endings.

Animals↗
PubMed2002

Modulation of QT interval during autonomic nervous system blockade in humans.

BACKGROUND: It is thought that the autonomic nervous system modulates QT interval, but traditional autonomic blockade combining propranolol and atropine has produced conflicting results. We used the alternative approach of interrupting neurotransmission at the level of autonomic ganglia to determine its effect on the QT interval. METHODS AND RESULTS: We infused trimethaphan at increasing doses (0.5 to 10 mg/min IV) while monitoring heart rate, heart rate variability spectra, QT interval, and blood pressure in 10 normal volunteers, 9 patients with multiple system atrophy (MSA), and 8 patients with pure autonomic failure (PAF). The QT interval was corrected for heart rate using Bazett's formula (QTc). Patients with PAF had very low heart rate variability and a prolonged QTc at baseline (465+/-8 ms) compared with patients with MSA (448+/-6 ms) and normal subjects (432+/-6 ms). In normal subjects, trimethaphan dose-dependently prolonged QTc (to 469+/-7 ms), decreased RR interval (995+/-45 to 670+/-35 ms), and abolished heart rate variability. In MSA patients, trimethaphan also prolonged QTc (to 463+/-7 ms) and reduced heart rate variability but did not significantly change RR interval (from 813+/-38 to 801+/-39). CONCLUSIONS: Autonomic blockade prolongs QT interval in normal subjects to a similar duration as in PAF patients. Furthermore, blocking residual autonomic tone in PAF patients is associated with a further increase in QT interval length. Patients with MSA have greater residual sympathetic tone and greater prolongation of the QT interval during ganglionic blockade than PAF patients.

Aged↗
PubMed2002

Increased sympathetic activation in idiopathic orthostatic intolerance: role of systemic adrenoreceptor sensitivity.

Idiopathic orthostatic intolerance (OI) is characterized by adrenergic symptoms with standing. Changes in central sympathetic tone or in adrenoreceptor sensitivity could contribute to this syndrome. In OI patients and control subjects, we determined heart rate (HR) and systolic blood pressure (SBP) changes after incremental bolus doses of isoproterenol and phenylephrine before and during ganglionic blockade with trimethaphan. SBP decreased by 17+/-1.6 mm Hg in patients and 3.9+/-3.8 mm Hg in control subjects (P<0.01) with trimethaphan. Patients with a larger decrease (28+/-3.8 mm Hg, n=7) in SBP with trimethaphan had greater supine SBP and supine and upright plasma norepinephrine levels than did patients with a lesser decrease (3.0+/-3.0 mm Hg, n=7) in SBP. Supine and orthostatic HRs were similar for the groups. The majority of patients had a normal HR response to isoproterenol before and during ganglionic blockade. Phenylephrine increased SBP similarly in patients and control subjects before and during blockade. Sympathetic support is increased in a subgroup of OI patients. Hyperadrenergic and nonhyperadrenergic subgroups have similar degrees of orthostatic tachycardia. Our findings suggest that the hyperadrenergic features of OI cannot be completely explained by systemic hypersensitivity of postsynaptic alpha(1)- and beta-adrenoreceptors but rather originates in enhanced sympathetic activation.

Adrenergic alpha-Agonists↗