Intravenous glycerol vs dexamethasone therapy in the management of acute cerebral oedema in patients with acute cerebral infarction.
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Biomedical subjects
Publications and source records attributed to R K Goyal.
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The effects of 5-hydroxytryptamine (5HT) and noradrenaline (NA) have been studied on rat anococcygeus muscle. 1. 5HT and NA produced a dose-dependent contraction of rat anococcygeus muscle. Cyproheptadine (1.0 X 10(-6) M), a specific 5HT receptor blocker, failed to inhibit the responses to either 5HT or NA. 2. However, phentolamine, a specific alpha receptor antagonist competitively blocked the responses to 5HT and NA. 3. The responses to 5HT were inhibited in the reserpinized (5 mg/kg i.p. 24 h) and 6-hydroxydopamine (6-OHDA) pre-treated preparations. 6-OHDA produced a leftward shift of the dose-response curve of NA. Reserpine pre-treatment potentiated lower doses of NA and the threshold dose of NA was significantly decreased. 4. Nialamide (2.2 x 10(-6) M), the mono-amine oxidase inhibitor produced a significant leftward shift of the dose-response curve of both 5HT and NA. Pyrogallol (2.3 x 10(-5) M), the catechol-o-methyl transferase inhibitor also potentiated the responses to both 5HT and NA, but the potentiation was significant at lower doses of 5HT and NA. 5. Our data suggest that 5HT- and NA-induced contractions in rat anococcygeus muscle are mediated through common alpha adrenoceptors. 5HT actions are probably indirect, mediated through the release of NA.
The effects of histamine and its analogs 2-(2-pyridyl) ethylamine (PEA) and 4-methylhistamine (4 MH) have been studied on uterine preparations obtained from estrogen-primed guinea pigs and rats. (1) Histamine and 4 MH, a specific H2-receptor agonist produced relaxation in estrogen-primed rat uterus, whereas these agonists produced contraction in the estrogen-primed guinea pig uterus. (2) PEA, a specific H1-receptor agonist produced contraction in the guinea pig uterus but had no effect on the rat uterus. (3) Metiamide blocked responses to histamine and 4 MH in the rat uterus, whereas mepyramine blocked responses to histamine and PEA in the guinea pig uterus. (4) Propranolol produced competitive antagonism with histamine in the rat uterus, whereas it had no significant effect on the histamine or PEA responses in the guinea pig uterus. (5) Reserpine pretreatment completely abolished the responses to histamine and 4 MH in the rat uterus but did not alter the response in the guinea pig uterus. (6) Our data suggest that in rat uterus only H2-receptors are present and they are indirectly through the release of noradrenaline. In the guinea pig uterus both H1- and H2-receptors are present and are excitatory and directly acting.
Experiments were performed in anesthetized opossums. Electrical and mechanical activity was recorded simultaneously from the esophageal body at 5, 3, and 1 cm above the lower esophageal sphincter (LES). Esophageal responses were evoked by electrical stimulation of vagal efferents or by induced swallowing. Electrical and mechanical activity was associated in 86% and dissociated in 14% of the 1,200 responses examined. The frequency of dissociation was dependent on the site in the esophagus and the frequency of vagal efferent stimulation (P less than 0.05). The interval between the onset of electrical and mechanical events, called electromechanical delay, had a regional gradient: 5 cm above LES greater than 3 cm greater than 1 cm (P less than 0.01). This delay was also dependent on the frequency of stimulation. The amplitude of spike burst and the number of spikes in a burst closely correlated with the amplitude of contraction. These studies show that electromechanical responses and dissociations are dependent on the regional level in the esophagus and the frequency of vagal stimulation.
Experiments were performed on anesthetized opossums to study the influence of vagal efferent stimulation on peristalsis in the esophageal smooth muscle using various stimulus parameters. Current intensity, pulse duration, frequency, and train duration were varied systematically. Electrical and mechanical activities were recorded simultaneously at 5, 3, and 1 cm above the lower esophageal sphincter (LES). Vagal efferent stimulation produced a spike burst and contraction with a latency after the termination of the stimulus. This latency varied at different sites with the same stimulus parameters. For example, a stimulus of 5 mA, 0.5 ms, 10 Hz, and 1-s train produced latencies for the electrical response of 1.48 +/- 0.04, 2.2 +/- 0.12, and 3.5 +/- 0.09 s (+/- SEM) at 5, 3, and 1 cm above LES, respectively. The differences in latency were statistically significant (P less than 0.01). The latency of response at any one site also changed with different stimulus parameters; e.g. at 1 cm above LES, the latency of electrical response at 10 Hz was 3.5 +/- 0.09 s, but at 20 Hz the latency was 2.01 +/- 0.06 s when current intensity, pulse, and train duration remained at 5 mA, 0.5 ms, and 1 s. This decrease in latency with increasing frequency was statistically significant (P less than 0.01). By changing stimulus parameters, antiperistalsis or peristalsis with different speeds of propagation could be induced. Antiperistalsis or simultaneous responses occurred near threshold stimulus parameters. Suprathreshold stimuli produced peristaltic responses. Speed of peristalsis in the distal esophagus was 1.82 +/- 0.08 cm/s with swallowing, which was not different from 1.98 +/- 0.14 cm/s (P greater than 0.05) with vagal stimulation of 5 mA, 0.5 ms, 10 Hz, and 1-s train. These studies suggest that: (a) peristalsis in the smooth muscle part of the esophagus can be explained entirely on the basis of peripheral mechanisms, and (b) the central nervous system may modulate the occurrence, polarity, and speed of propagation by modifying the intensity and frequency of vagal activation.
Many peripheral autonomic nerves are neither cholinergic nor adrenergic. Such nerves are widely distributed in the gastrointestinal, urogenital and respiratory tracts, and in blood vessels. The nature of their neurotransmitter is not known. We have previously reported that vasoactive intestinal polypeptide (VIP) is a potent inhibitor of opossum lower oesophageal sphincter (LOS) and that its inhibitory effect is exerted directly on the sphincter muscle. Subsequent studies have confirmed the inhibitory effect of VIP on LOS in other species. Recently, very high tissue levels of VIP have been reported in the LOS and other gastrointestinal sphincters. Furthermore, VIP has been localized to intramural neurones and is released upon electrical stimulation of the vagus nerve. We report here that immunoantagonism of VIP with a high-titre antiserum antagonized inhibitory neuromuscular transmission in the LOS. These findings provide evidence of a role for VIP as an inhibitory neurotransmitter.
Histamine, 2-(2-pyridyl)ethylamine (PEA), a specific H1 receptor agonist, and 4-methylhistamine (4-MH), a specific H2 receptor agonist, produced a dose-dependent contraction of estrogen-primed guinea pig uterus and taenia coli. Mepyramine (10(-7) M), a specific H1 receptor antagonist, competitively blocked the responses to histamine and PEA in both the preparations. Metiamide (10(-6) M), a specific H2 receptor antagonist, inhibited the responses to histamine and 4-MH in the guinea pig uterus and taenia coli. Our data suggest the presence of both H1 and H2 receptors in the guinea pig uterus and taenia coli. Both receptors appear to be excitatory in nature.
Infusions of verapamil (V) and sodium nitroprusside (NP) caused dose-dependent reductions in the lower esophageal sphincter pressure (LESP) in anesthetized opossums. Verapamil caused a gradual fall during the infusion and a gradual recovery upon cessation of the infusion. On the other hand, NP caused a prompt reduction and a prompt recovery. Both the agents also caused a fall in arterial blood pressure, but the fall in LESP was not related to the fall in the blood pressure. Both the agents antagonized the tonic and the phasic components of the LESP and, in large doses, both drugs almost abolished the LESP. Esophageal contractions were also antagonized by both agents, although verapamil was more effective than nitroprusside in this regard. These studies show that phasic and tonic components of LESP are not related to distinctive verapamil and nitroprusside sensitive calcium activation systems. Moreover, the V- and NP-sensitive calcium activation systems may lie in series rather than parallel.
Experiments were performed in anesthetized opossums to study the nature of vagal control on the small bowel. Electrical activity was recorded in the duodenum, jejunum, and ileum with silver chloride electrodes. Slow waves and spike potentials were observed at all three sites. There was a decreasing frequency gradient of slow waves and the incidence of slow waves with spikes in the aboral direction. Vagotomy had no effect on the electrical activity. Vagal stimulation at threshold stimuli inhibited spike potentials in all three segments of small intestine, but slow waves were not affected. Vagal stimulation after sectioning of the gut proximal to the electrodes converted the response from inhibition to excitation. These studies suggest that a) vagus carries both excitatory and inhibitory influences to the small bowel; b) inhibitory influences are dominant in the intact opossum small intestine; and c) the nature of the response obtained with vagal stimulation may be explained on the basis of the paths taken by inhibitory and excitatory fibers.
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Studies were performed on anesthetized opossums. Lower esophageal sphincter pressures were measured with waterfilled and continously perfused catheters anchored in the sphincter. Administration of adenosine 5'-triphosphate (ATP) and ADP in the left gastric artery usually produced an initial contraction followed by a more prolonged inhibition. Adenosine, on the other hand, produced only inhibition. The effect of ATP was not modified by phentolamine (1 mg/kg), propranolol (1 mg/kg) or atropine (30 micrograms/kg). Tetrodotoxin partially antagonized (P less than 0.05) the inhibitory effects of ATP and adenosine, but augmented the excitatory effect of ATP (P less than 0.05). 2-2'-Pyridylisatogen tosylate selectively antagonized the effects of ATP without modifying the effect of adenosine. This antagonist, however, did not modify the resting sphincter pressure or the vagal stimulated sphincter relaxation. Dipyridamole enhanced the inhibitory effect of adenosine, but did not augment vagal stimulates sphincter relaxation. There was no cross-tachyphylaxis between ATP and adenosine. Tachyphylaxis, either to ATP or adenosine, did not inhibit the vagal stimulated sphincter relaxation. These studies show that: (a) ATP and adenosine may act on different receptor sites to modify sphincter pressure; (b) only a small part of the inhibitory effect of ATP and adenosine is mediated by the inhibitory neurons; (c) neither ATP nor adenosine appears to be the inhibitory transmitter released by the noncholinergic, nonadrenergic inhibitory neurons in the vagal pathway to the lower esophageal sphincter.
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Studies were performed in anesthetized opossums to investigate the nature of vagal-stimulated sphincter relaxation, which is resistant to antagonism by a combination of hexamethonium and atropine. The sphincter pressures were measured with water-filled and continuously perfused catheters anchored in the lower esophageal sphincter. Neither increase in the doses of hexamethonium and atropine nor addition of diphenhydramine further modified the vagal response. However, administration of 5-methoxydimethyltryptamine in the presence of hexamethonium and atropine abolished vagally stimulated sphincter relaxation. In animals pretreated with parachlorophenylalanine, addition of atropine and hexamethonium also abolished vagally stimulated sphincter relaxation. In the experiments in which lower esophageal sphincter relaxation on vagal stimulation was abolished, the local stimulation of intramural neurons still produced normal lower esophageal sphincter relaxation. These studies suggest that 5-hydroxytryptamine may participate in the vagal inhibitory pathway to the lower esophageal sphincter.
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Studies were performed in the opossum to evaluate the morphological characteristics of the lower esophageal sphincter. The sphincter and the esophageal body were identified manometrically and fixed in situ by perfusion with aldehyde fixative. Light microscopy revealed that: (1) longitudinal muscle layers of the sphincter and the esophageal body were similar in thickness and compactness, and (2) circular muscle of the sphincter was thicker and was composed of muscle fasciculi with abundant intervening connective tissue as compared to the compact muscle fasciculi of the circular muscle of the esophageal body. Electron microscopy showed the circular muscle fibers of the sphincter to have irregular protuberances from their surfaces, whereas the circular muscle fibers of the esophageal body possessed smooth surfaces. Several types of junctional complexes between adjacent muscle fibers were observed; however, there was no difference in their distribution in the sphincter or esophageal body. The majority of the nerve varicosities contained a mixture of agranular (350 to 450 A) and large dense core vesicles (800 to 1600 A); varicosities containing small granular vesicles were not found in any area of the esophagus. When varicosities were cut along the longitudinal axis of the axon, they often showed grouping of similar vesicle types in different areas along the axon varicosities. There was no difference in the type of varicosities found in the sphincter or the esophageal body. These studies show that: (1) circular muscle of the sphincter can be morphologically distinguished from that of the esophageal body; (2) there is no difference in the morphology of the nerve terminals or the vesicle types in the two areas; and (3) classification of the varicosities based upon the predominance of the vesicle types may be artifactual because of sampling error.