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PubMed1986

Effect of ganglionic blockade on endogenous circulating pancreatic polypeptide, vasoactive intestinal polypeptide, substance P, neurotensin and noradrenaline in healthy controls and long-term insulin-dependent diabetic patients.

Plasma pancreatic polypeptide (PP), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT) and noradrenaline (NA) were measured in eight healthy subjects and 12 long-term insulin-dependent diabetic patients with and without autonomic neuropathy, before and after intravenous infusion of the ganglionic blocking agent trimethaphan camsylate, in order to determine the influence of the autonomic nervous system on the baseline values of the substances. The basal levels of the measured substances were not significantly different in healthy subjects and patients with or without diabetic autonomic neuropathy. In healthy subjects, the ganglionic blockade induced a significant decrease in PP (80%) (P less than 0.02), NA (58%) (P less than 0.05), NT (27%) (P less than 0.05) and a significant increase in SP (30%) (P less than 0.05), while the VIP concentration remained unchanged. The diabetic patients had nearly the same significant decrease in PP (68%) (P less than 0.01), NA (50%) (P less than 0.01), NT (22%) (P less than 0.02), VIP (21%) (P less than 0.05) and increase in SP (73%) (P less than 0.01). No relationship was found between the autonomic neuropathy and changes of the substances during ganglionic blockade. The results indicate that the postganglionic part of the autonomic nervous system participates in the maintenance of a normal baseline level of PP, NT and NA, but not of VIP. The regulation of VIP may be disturbed in long-term diabetic subjects.

Adult↗
PubMed1998

Internal jugular venous spillover of noradrenaline and metabolites and their association with sympathetic nervous activity.

It is recognized that the brain plays a pivotal role in the maintenance of blood pressure and the control of myocardial function. By combining direct sampling of internal jugular venous blood with a noradrenaline isotope dilution method, for examining neuronal transmitter release, and microneurographic nerve recording, we were able to quantify the release of central nervous system noradrenaline and its metabolites and investigate their association with efferent sympathetic nervous outflow in healthy subjects and patients with pure autonomic failure. To further investigate the relationship between brain noradrenaline, sympathetic nervous activity and blood pressure regulation we examined brain catecholamine turnover, based on the internal jugular venous overflow of noradrenaline and its principal central nervous system metabolites, in response to a variety of pharmacological challenges. A substantial increase was seen in brain noradrenaline turnover following trimethaphan, presumably resulting from a compensatory response in sympathoexcitatory forebrain noradrenergic neurones in the face of interruption of sympathetic neural traffic and reduction in arterial blood pressure. In contrast, reduction in central nervous system noradrenaline turnover accompanied the blood pressure fall produced by intravenous clonidine administration, thus representing the blood pressure lowering action of the drug. Following vasodilatation elicited by intravenous adrenaline infusion, brain noradrenaline turnover increased in parallel with elevation in muscle sympathetic nervous activity. While it is difficult to assess the source of the noradrenaline and metabolites determined in our studies, available evidence implicates noradrenergic cell groups of the posterolateral hypothalamus, amygdala, the A5 region and the locus coeruleus as being involved in the regulation of sympathetic outflow and autonomic cardiovascular control.

Adolescent↗
PubMed1999

Effects of controlled hypotension with sevoflurane anaesthesia on hepatic function of surgical patients.

The effects of controlled hypotension induced with trimethaphan (TMP), nitroglycerin (TNG) or prostaglandin E1 (PGE1) during sevoflurane anaesthesia on hepatic function were studied in 28 patients undergoing spinal fusion surgery. Patients were randomly divided into three groups to receive TMP (group A, n = 10), TNG (group B, n = 10) or PGE1 (group C, n = 8). Anaesthesia was maintained with N2O and sevoflurane. The mean arterial blood pressure was maintained at 60 mmHg for 90 min. Measurements included arterial ketone body ratio (AKBR-acetoacetate/3-hydroxybutyrate), SGOT, SGPT, LDH, blood glucose and blood gases were made. Measurements were taken before hypotension, 60 min and 90 min after starting hypotension, 60 min after recovery from hypotension and on the post-operative day. AKBR showed no significant change. SGOT, SGPT and LDH were within normal limits. Controlled hypotension induced with TMP, TNG or PGE1 under sevoflurane anaesthesia in surgical patients did not cause hepatocellular damage.

Adult↗
PubMed1997

Changes in cerebral blood flow accompanied with reduction of blood pressure treatment in patients with hypertensive intracerebral hemorrhages.

Blood pressure usually is reduced in patients with hypertensive intracerebral hemorrhage for the prevention of the expansion of the hematoma and recurrent hemorrhage in acute stage. However, disturbed autoregulation of cerebral circulation is expected, and decreased cerebral blood flow (CBF) caused by excessive hypotension has been pointed out. There are different mechanisms of action in hypotensives, thereby the influence of hypotension on CBF in patients with the thalamic hemorrhage was investigated using nitroglycerin (TNG), diltiazem hydrochloride (DH) and trimethaphan camsilate (TC). Average CBF in a hemisphere on the hematoma side, the hemisphere without hematoma, and around the hematoma showed a slight decline after administration of TNG or DH. However, CBF declined more, after TC than DH. DH and TNG are preferable in descending order to control blood pressure of patients with intracerebral hemorrhage in the acute stages in view of a smaller decline in CBF.

Adult↗
PubMed1993

Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats.

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.

Animals↗
PubMed1999

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance.

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

Adult↗
PubMed1981

Consumption of vitamin B12 during sodium nitroprusside administration in humans.

In view of evidence suggesting possible participation of cobalamin in cyanide metabolism, the effects of sodium nitroprusside (SNP) infusion on blood cyanide and plasma thiocyanate levels and serum vitamin B12 levels were examined in ten patients undergoing major orthopedic procedures. Whole blood cyanide concentrations increased significantly (P less than 0.001) from 3.6 +/- 1.1 to 65.7 +/- 16.2 micrograms/dl, and total serum B12 values decreased significantly (P less than 0.005) from 482 +/- 56 to 267 +/- 42 pg/ml, three hours after SNP therapy. Plasma thiocyanate did not change. Cyanide released from SNP converts hydroxocobalamin to cyanocobalamin, which is readily excreted in urine. These variables were not changed in six patients (control) who received trimethaphan. In vitro experiments revealed that none of the serum factor(s) nor nitroprusside interfered with the assay of B12. Hydroxocobalamin may be an appropriate adjunct during SNP therapy.

Adolescent↗
PubMed1983

Blood-brain barrier function following drug-induced hypotension in the dog.

To examine the effects of hypotension induced either with trimethaphan (TMP) or nitroprusside (NTP) on blood-brain barrier (BBB), penetration of Evans blue (EB) was observed in dogs anesthetized with halothane. Dogs given TMP were divided into two groups: Group 1, seven dogs rendered hypotensive to mean cerebral perfusion pressure (CPP) of 45 mmHg for 45 min and then of 30 mmHg for 45 min; Group 2, three dogs examined 3 days after arterial hypotension identical to that in Group 1. Dogs given NTP were divided into four groups: Group 1, seven dogs rendered hypotensive with NTP (at dose less than 1 mg/kg) identical to the TMP-Group 1; Group 2, three dogs examined as the TMP-Group 2; Group 3, seven dogs rendered hypotensive to CPP 45 mmHg for 45 min; Group 4, seven dogs rendered hypotensive with NTP (at dose greater than 1 mg/kg) identical to the NTP-Group 1. In all dogs, the dorsal cortical surface and standardized serial coronal sections were examined for evidence of EB penetration. The mean EB penetration score (+/- SEM) for TMP-Groups 1 and 2 was 12 +/- 6, 0 +/- 0, respectively, and for NTP-Groups 1, 2, 3, and 4 was 105 +/- 14, 30 +/- 7, 6 +/- 6, and 125 +/- 26, respectively. These results suggest that dysfunction of the BBB in the NTP group was more pronounced than in the TMP group.

Anesthesia↗
PubMed1983

Augmentation of surviving flap area by intraarterial vasodilators administered through implantable pumps.

Using the implantable Infusaid Model 300 pump, several vasodilators (prostaglandin E1, isoxsuprine, bradykinin, trimethaphan, and reserpine) were infused intraarterially into an abdominal island flap in the rabbit. All produced a large increase in flap surviving area over saline controls at forty-eight hours, measuring as high as a 2.8-fold increase in random portions of the flap with prostaglandin E1. The agents possessed differing modes of action but had the common property of vasodilatation. The results raise questions concerning the possible physiological role of endogenous prostaglandins in the surgical delay phenomenon. The Infusaid pump was a valuable tool in the study and was well tolerated by the animals.

Alprostadil↗
PubMed1975

Anesthesia for intracranial aneurysms.

At the Medical University of South Carolina during the past five years, 62 patients have had intracranial aneurysm surgery, with an overall mortality of 4.8%. Anesthesia was given by me to 14 of these patients. Preoperatively these patients were placed on bedrest, steroid prophylaxis, and sedative and antihypertensive medication to reduce th possibility of recurrent subarrachnoid hemorrhage. Halothane-nitrous oxide-oxygen endotracheal anesthesia with controlled ventilation was used, with careful monitoring of EKG, direct arterial pressure, arterial blood gases, body temperature, and urinary output. Adjuncts for control of bleeding and intracranial pressure were osmotic diuresis, cerebrospinal fluid drainage, minimal head-up tilt, and controlled hypotension using trimethaphan (Arfonad). There were no operative deaths, although one patient died postoperatively. Three patients had neurologic deficitys. These data indicate that controlled hypotension is a safe technic which, when properly used, can reduce the risk of anesthesia for intracranial aneurysm surgery.

Adolescent↗
PubMedDate not supplied

Neuropharmacologic distinction of neurogenic orthostatic hypotension syndromes.

BACKGROUND: Neurogenic orthostatic hypotension (OH) characterizes pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure. We used neuropharmacologic probes that might distinguish these diseases based on loss of sympathetic noradrenergic nerves in PAF and PD + OH but not in MSA, and related the results to neurochemical and neuroimaging findings in the same patients. METHODS: Patients with neurogenic OH (PD + OH; N = 35), MSA (N = 41), and PAF (N = 12) received iv trimethaphan (TRI), which inhibits sympathetic nerve traffic, or yohimbine (YOH), which stimulates sympathetic traffic. Dependent measures included blood pressure, plasma norepinephrine (NE) levels, and interventricular septal myocardial radioactivity after iv injection of the sympathoneural imaging agent, 6-[F]fluorodopamine. RESULTS: The PD + OH and PAF groups had smaller pressor responses to YOH (12 +/- 8 and 13 +/- 1 mm Hg) and depressor responses to TRI (-14 +/- 8 and -17 +/- 7 mm Hg) than did the MSA group (43 +/- 8 mm Hg, -57 +/- 8 mm Hg; P = 0.01, P = 0.03). The PD + OH and MSA groups did not differ in NE responses to YOH and TRI. The depressor response to TRI, the pressor response to YOH, and the blood pressure difference between YOH and TRI all correlated positively with myocardial 6-[F]fluorodopamine-derived radioactivity. CONCLUSIONS: The PD + OH resembles PAF and differs from MSA in hemodynamic responses to drugs that alter NE release from sympathetic nerves. The results fit with sympathetic noradrenergic denervation in PD + OH and PAF but not in MSA.

Blood Pressure↗
PubMed1992

A novel cholinergic receptor mediates inhibition of chick cochlear hair cells.

The central nervous system provides feedback regulation at several points within the peripheral auditory apparatus. One component of that feedback is inhibition of cochlear hair cells by release of acetylcholine (ACh) from efferent brainstem neurons. The mechanism of hair cell inhibition, and the character of the presumed cholinergic receptor, however, have eluded understanding. Both nicotinic and muscarinic, as well as some non-cholinergic ligands can affect the efferent action. We have made whole-cell, tight-seal recordings from short (outer) hair cells isolated from the chick's cochlea. These are the principal targets of cochlear efferents in birds. ACh hyperpolarizes short hair cells by opening a cation channel through which Ca2+ enters the cell and subsequently activates Ca(2+)-dependent K+ current (Fuchs & Murrow 1991, 1992). Both curare and atropine are effective-antagonists of cholinergic inhibition at 3 microM, whereas trimethaphan camsylate and strychnine block at 1 microM. The normally irreversible nicotinic antagonist, alpha-bungarotoxin, reversibly blocked the hair cell response, as did kappa-bungarotoxin. The half-blocking concentration for alpha-bungarotoxin was 26 nM. It is proposed that the hair cell AChR is a ligand-gated cation channel related to the nicotinic receptor of nerve and muscle.

Acetylcholine↗
PubMed2005

Ganglion blockade does not prevent cortisol-induced hypertension in man.

1. The aim of the present study was to assess the effect of ganglion blockade on blood pressure in cortisol treated human subjects. 2. Four healthy male subjects were treated with cortisol 80 mg/day for a 5-day period. Ganglion blockade was achieved by intravenous trimethaphan. 3. Ganglion blockade did not significantly alter blood pressure in the pretreatment phase or on the last day of cortisol treatment. 4. Taken together with our previous observations that sympathetic activity is unaltered or reduced by cortisol, these results suggest that cortisol induced hypertension in humans is not a result of overactivity of the autonomic nervous system.

Autonomic Nervous System↗
PubMed1993

Evidence for an adrenergic innervation of the adrenal cortical blood vessels in rats.

The aim of this study was to investigate the blood flow in the adrenal cortex of the rat. Relative changes in the adrenal cortical blood flow were continuously measured by Laser Doppler flowmetry in 33 chloralose-anaesthetized artificially ventilated rats during electrical stimulation (1 ms, 5 V) of the left great splanchnic nerve (LGSN), which conveys both pre- and post-ganglionic nerve fibres to the adrenal gland. Laser Doppler flux (LDF) was decreased and regional resistance (RR) was increased by augmenting nerve stimulation at increasingly higher frequencies (2, 4, 8, 20 and 40 Hz). The decrease in LDF, when compared to pre-drug stimulations at 4 Hz was partially or totally inhibited by the adrenergic blocking agents trimethaphan (TRIM), guanethidine (GUA) and alpha 1-blockade with prazosin (PRAZ). Furthermore, both the decrease in LDF and the increase in RR were either completely or partially blocked by stimulation at 40 Hz after TRIM-treatment and GUA-treatment. It is concluded that the adrenal cortex in the rat is innervated by post-ganglionic adrenergic nerve fibres, which are involved in the regulation of blood flow in the adrenal cortex.

Adrenal Cortex↗
PubMed1995

Sympathetic nervous system effects on feline bladder wall compliance throughout continence.

The urinary bladder is a compliant organ, high compliance being essential for useful urine storage. The extent to which the sympathetic nervous system promotes the storage of urine by increasing bladder compliance is unclear. The aim of the present study was to determine the range of bladder volumes over which the sympathetic nervous system increased bladder wall compliance. In supine, anaesthetized cats, the bladder was filled at twice the rate of natural filling, the continence cycle being interrupted at five stages. These stages were when the bladder had become globular, during prodromal contractions, soon after non-micturating contractions had commenced, approximately two-thirds of the way through the continence cycle and just prior to micturition. During each of these interruptions, bladder volume was held constant while pelvic nerve afferent activity and bladder pressure were recorded. Recordings were obtained before and during the intravenous infusion of trimethaphan, the resulting partial ganglion blockade decreasing arterial pressure by a third. Bladder pressure as well as afferent nerve activity increased significantly when the sympathetic drive was transiently blocked, indicating that there had been a prevailing net sympatho-inhibitory effect promoting bladder wall relaxation. This effect was observed during prodromal contractions and continued until the onset of micturition. This net sympatho-inhibitory effect is a potential therapeutic path for the treatment of bladder storage disorders.

Animals↗
PubMed1995

Involvement of vasodilator mechanisms in arterial pressure lability after sino-aortic baroreceptor denervation in rat.

1. To examine the regional haemodynamic basis of arterial pressure lability seen after sino-aortic baroreceptor denervation (SAD), simultaneous beat-to-beat recordings of arterial pressure and indices of regional blood flows (Doppler probes around the subdiaphragmatic and lower abdominal aortae and the superior mesenteric artery) were performed in the same conscious rats (n = 7) before, 1 and 14 days after SAD. 2. Acute SAD increased arterial pressure, decreased regional blood flows and vascular conductances, and potentiated the depressor and vasodilator effects of ganglionic blockade with trimethaphan, suggesting sympathetic overactivity. All parameters chronically returned to or near normal. 3. Both acute and chronic SAD increased the variability of arterial pressure and of regional conductances. Arterial pressure lability was characterized by a mixture of depressor and pressor events which were associated with regional vasodilatations and vasoconstrictions, respectively. This haemodynamic pattern was not affected by acute beta-adrenoceptor blockade with propranolol. 4. In conscious rats, the baroreceptor reflex acts to buffer the spontaneous variability of regional vascular conductances and thereby stabilizes arterial pressure. Sino-aortic baroreceptor denervation-induced arterial pressure lability does not depend on the level of sympathetic activation, and is determined by the relative contribution of depressor and pressor events accompanied by extensive vasodilatations and vasoconstrictions, respectively. Vasodilatations are not caused by the stimulation of vascular beta 2-adrenoceptors.

Animals↗
PubMed2002

Mechanism of blood pressure and R-R variability: insights from ganglion blockade in humans.

Spontaneous blood pressure (BP) and R-R variability are used frequently as 'windows' into cardiovascular control mechanisms. However, the origin of these rhythmic fluctuations is not completely understood. In this study, with ganglion blockade, we evaluated the role of autonomic neural activity versus other 'non-neural' factors in the origin of BP and R-R variability in humans. Beat-to-beat BP, R-R interval and respiratory excursions were recorded in ten healthy subjects (aged 30 +/- 6 years) before and after ganglion blockade with trimethaphan. The spectral power of these variables was calculated in the very low (0.0078-0.05 Hz), low (0.05-0.15 Hz) and high (0.15-0.35 Hz) frequency ranges. The relationship between systolic BP and R-R variability was examined by cross-spectral analysis. After blockade, R-R variability was virtually abolished at all frequencies; however, respiration and high frequency BP variability remained unchanged. Very low and low frequency BP variability was reduced substantially by 84 and 69 %, respectively, but still persisted. Transfer function gain between systolic BP and R-R interval variability decreased by 92 and 88 % at low and high frequencies, respectively, while the phase changed from negative to positive values at the high frequencies. These data suggest that under supine resting conditions with spontaneous breathing: (1) R-R variability at all measured frequencies is predominantly controlled by autonomic neural activity; (2) BP variability at high frequencies (> 0.15 Hz) is mediated largely, if not exclusively, by mechanical effects of respiration on intrathoracic pressure and/or cardiac filling; (3) BP variability at very low and low frequencies (< 0.15 Hz) is probably mediated by both sympathetic nerve activity and intrinsic vasomotor rhythmicity; and (4) the dynamic relationship between BP and R-R variability as quantified by transfer function analysis is determined predominantly by autonomic neural activity rather than other, non-neural factors.

Adult↗
PubMed2003

Mechanisms of the cerebrovascular response to apnoea in humans.

We measured ventilation, arterial O2 saturation, end-tidal CO2 (PET,CO2), blood pressure (intra-arterial catheter or photoelectric plethysmograph), and flow velocity in the middle cerebral artery (CFV) (pulsed Doppler ultrasound) in 17 healthy awake subjects while they performed 20 s breath holds under control conditions and during ganglionic blockade (intravenous trimethaphan, 4.4 +/- 1.1 mg min-1 (mean +/- S.D.)). Under control conditions, breath holding caused increases in PET,CO2 (7 +/- 1 mmHg) and in mean arterial pressure (MAP) (15 +/- 2 mmHg). A transient hyperventilation (PET,CO2 -7 +/- 1 mmHg vs. baseline) occurred post-apnoea. CFV increased during apnoeas (by 42 +/- 3 %) and decreased below baseline (by 20 +/- 2 %) during post-apnoea hyperventilation. In the post-apnoea recovery period, CFV returned to baseline in 45 +/- 4 s. The post-apnoea decrease in CFV did not occur when hyperventilation was prevented. During ganglionic blockade, which abolished the increase in MAP, apnoea-induced increases in CFV were partially attenuated (by 26 +/- 2 %). Increases in PET,CO2 and decreases in oxyhaemoglobin saturation (Sa,O2) (by 2 +/- 1 %) during breath holds were identical in the intact and blocked conditions. Ganglionic blockade had no effect on the slope of the CFV response to hypocapnia but it reduced the CFV response to hypercapnia (by 17 +/- 5 %). We attribute this effect to abolition of the hypercapnia-induced increase in MAP. Peak increases in CFV during 20 s Mueller manoeuvres (40 +/- 3 %) were the same as control breath holds, despite a 15 mmHg initial, transient decrease in MAP. Hyperoxia also had no effect on the apnoea-induced increase in CFV (40 +/- 4 %). We conclude that apnoea-induced fluctuations in CFV were caused primarily by increases and decreases in arterial partial pressure of CO2 (Pa,CO2) and that sympathetic nervous system activity was not required for either the initiation or the maintenance of the cerebrovascular response to hyper- and hypocapnia. Increased MAP or other unknown influences of autonomic activation on the cerebral circulation played a smaller but significant role in the apnoea-induced increase in CFV; however, negative intrathoracic pressure and the small amount of oxyhaemoglobin desaturation caused by 20 s apnoea did not affect CFV.

Adrenergic alpha-Agonists↗