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Biomedical subjects

V S Murthy

Publications and source records attributed to V S Murthy.

At least 37 records · Page 2Linked to original sources
PubMed1987

Esmolol: a titratable short-acting intravenous beta blocker for acute critical care settings.

Esmolol (Brevibloc) is an intravenous, short-acting, titratable, cardioselective beta blocker with a very rapid onset and offset of action (t1/2 = 9.2 minutes). Esmolol-induced beta blockade can be maintained as long as infusion is continued. It exhibits neither intrinsic sympathomimetic activity nor significant membrane-stabilizing activity. It is rapidly metabolized by an esterase in the erythrocyte cytosol to an inactive acid metabolite. Its hemodynamic and electrophysiologic effects are similar to those of other beta blockers. Unlike the effects of other beta blockers, however, the effects of esmolol dissipate rapidly to baseline within 30 minutes after its discontinuation. Evidence obtained from clinical studies indicates that esmolol is effective and safe in reducing the ventricular rate in patients with supraventricular tachyarrhythmias, and in reducing the heart rate in patients with acute myocardial infarction and/or unstable angina. Esmolol has also been shown to be effective and safe in attenuating the tachycardia and hypertension seen during the intraoperative period. Data from postoperative patients indicate that esmolol is ideal as sole-agent therapy for the treatment of moderate postoperative hypertension associated with a hyperdynamic state. The short duration of action and titratability of esmolol make it an ideal drug for use in patients in whom the clinical need for beta blockade is limited in duration, and it offers additional safety in patients in whom beta blockade is beneficial; however, it might be precluded because of coexisting contraindications. To date, experience with esmolol in over 1200 patients has been gathered, and the adverse effect profile is basically similar to that reported here.

Adrenergic beta-Antagonists↗
PubMed1987

Dissociation and diurnal variation of prostaglandin E2 6-keto-prostaglandin-F1-alpha, and thromboxane B2 excretion in healthy females.

The existence of diurnal variation in renal function is well described. Prostaglandins are intimately involved with renal physiology, yet a diurnal variation in their excretion is not well documented. We collected 12 consecutive 2 hour urine specimens from 10 young healthy females and measured prostaglandin E2 [PGE2], thromboxane B2 [TXB2], and 6-keto-prostaglandin-F1-alpha by radioimmunoassay for each specimen. We also measured urine volume, urine sodium, and urine creatinine levels. Regression analysis was used to determine the best sine curve for time versus each set of mean values. Only the urinary excretion of PGE2 and TXB2, as well as water were found to significantly fit the generated sine curves. The curves for PGE2 and TXB2 showed a temporal dissociation in their peak and trough values. The excretion of PGE2 between 0800 hours and 2000 hours was significantly higher than during the hours of 2000 and 0800. The opposite was true for the TXB2 excretion. This data suggests that these two prostaglandins and water are excreted in a sine wave pattern. It also suggests that the excretion of PGE2 and TXB2 may respond to different time associated stimuli. We also showed a significant correlation between PGE2 excretion and both the excretion of water and sodium.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effects of captopril on sympathetic control of the heart and vasculature in dogs.

Experiments were conducted in pentobarbital anesthetized dogs to investigate the effects of captopril on sympathetic neuronal control of the heart and hindlimb vasculature. Captopril, 3.1 mg/kg, i.v. produced marked reductions in blood pressure and hindlimb perfusion pressure, an observation consistent with the high plasma renin activity in the test animals. Increments in hindlimb perfusion pressure elicited by electrical stimulation of the lumbar sympathetic chain were also significantly reduced following captopril administration (p less than .002). The subsequent administration of a ten fold higher dose of captopril, 31.0 mg/kg, produced no further attenuation of the neurally mediated responses. In contrast to the decreased vascular responses to nerve stimulation after captopril, the tachycardia produced by stimulation of pre- or post-ganglionic neurons to the stellate ganglion were not altered. The results of the present study suggest that captopril acts by inhibiting vascular sympathetic neuronal function when the activity of the renin-angiotensin system is elevated. The attenuation of neurally mediated vasoconstriction may be due to the interruption of angiotensin II formation, thereby, preventing the facilitatory effects of angiotensin on sympathetic neurons.

Animals↗
PubMed1987

Controlled beta-receptor blockade with flestolol: a novel ultrashort-acting beta-blocker.

The pharmacological properties of an ultrashort-acting beta-receptor blocking agent, flestolol, were evaluated in rabbits. Infusion of graded doses (1-100 micrograms/kg/min, i.v.) into conscious rabbits produced dose-dependent bradycardia without any significant effect on mean arterial pressure. A desired level of heart rate could be obtained by either increasing or decreasing the dose infused. Such titration could be done by changing the dose of flestolol at 20-min intervals. Infusion of 31 micrograms/kg/min of flestolol into reserpinized, conscious rabbits had no effect on mean arterial pressure or heart rate but produced significant inhibition of isoproterenol-induced hypotension and tachycardia. This dose had no effect on the chronotropic and vascular effects of norepinephrine (NE), angiotensin II, adenosine, or acetylcholine. In these rabbits, flestolol was greater than 10-fold as active as esmolol, another ultrashort-acting beta-blocking agent, in inhibiting the responses to isoproterenol. In rabbits under pentobarbital anesthesia, infusion of flestolol (3.1, 10, and 31 micrograms/kg/min) produced dose-dependent beta-receptor blockade. On termination of a 70-min infusion, recovery of the responses to isoproterenol occurred within 30 min. In a separate series of experiments, the effects of infusion of flestolol (10 micrograms/kg/min) into the portal vein were compared with the effects of infusion of the same dose of flestolol into the femoral vein of anesthetized rabbits. Infusion into the femoral vein produced bradycardia and inhibited the hypotensive as well as cardioaccelerator effects of isoproterenol. Infusion into the portal vein was devoid of either effect, suggesting extensive inactivation by the liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

Transient pulmonary platelet sequestration during endotoxemia in dogs.

We evaluated the time-course of regional platelet sequestration, following a bolus dose of endotoxin in anesthetized dogs. Autologous indium 111 labeled platelets, representing less than 1% of the circulating platelets, were injected 35-60 min prior to administering endotoxin intravenously to dogs. A gamma camera was used to monitor the distribution of these platelets within the thorax and abdomen. Alterations in the circulating blood platelet count paralleled the changes in blood radioactivity, enabling us to use external imaging to evaluate platelet kinetics. Marked hypotension and thrombocytopenia occurred within 6 min after administering endotoxin. The platelet pool in the lungs peaked at 9 min and was temporally related to the decrease in circulating platelet count, hypotension and increase in liver size. Translocation of platelets from the lungs to the circulating platelet pool occurred during the subsequent hour with sequestration occurring in the liver and possibly other organs. During this phase there was a recovery in platelet count to 35% of baseline levels but without significant recovery in mean arterial pressure. Based on these results we propose that endotoxin-induced thrombocytopenia results from pulmonary and hepatic sequestration of platelets, but that sequestration of platelets in the lungs is only transient. The mechanism and significance of subsequent translocation of platelets from the lungs to other sites, particularly the liver and the circulating platelet pool, remain to be investigated.

Animals↗
PubMed1987

Evaluation of myocardial perfusion and coronary vascular resistance following withdrawal of chronic nitroglycerin treatment in rabbits.

This investigation was performed to determine whether the abrupt withdrawal of chronically administered nitroglycerin (NTG) alters coronary vascular resistance and myocardial perfusion in an experimental rabbit model. New Zealand white rabbits received 2 inches of topical NTG (2%) applied 3 times daily over a 6 week period. Forty hours after abrupt withdrawal of NTG left ventricular blood flow was assessed by the radioactive microsphere technique. Coronary resistance was significantly increased in NTG-withdrawal rabbits at the baseline (21.5 +/- 3.1) compared to controls (13.5 +/- 1.2) and remained elevated after ergonovine administration at both the early (NTG-withdrawal: 20.9 +/- 3.5 vs controls 12.6 +/- 1.5) and late (NTG-withdrawal: 17.1 +/- 3.1 vs controls: 11.6 +/- 0.9) sampling periods. Neither ergonovine nor indomethacin significantly altered blood flow compared to earlier values. However, the NTG-withdrawal rabbits exhibited significantly lower blood flow to the left ventricle compared to controls after ergonovine administration at both early (NTG-withdrawal: 4.80 +/- 0.72 ml/min/gram vs controls: 6.98 +/- 0.79 ml/min/gram) and late (NTG-withdrawal: 5.30 +/- 0.80 ml/min/gram vs controls: 7/52 +/- 0.66 ml/min/gram) sampling periods and also following indomethacin administration (NTG-withdrawal: 4.24 +/- 0.46 ml/min/gram vs controls: 7.52 +/- 1.26 ml/min/gram). Electrocardiographic evidence of myocardial ischemia was noted in the NTG-withdrawal rabbits following intracardiac injection of microspheres. These studies show that increased sensitivity of NTG-withdrawal rabbits to ergonovine or microsphere injection is associated with increased coronary vascular resistance. However, severe myocardial ischemia was not observed.

Animals↗
PubMed1986

Esmolol and the adrenergic response to perioperative stimuli.

Esmolol, an ultra-short-acting, cardioselective, beta-receptor blocking agent, has been developed for use in clinical conditions requiring controlled beta-receptor blockade. Its esterase-induced rapid metabolic inactivation and resulting brief pharmacologic effect provides control over the magnitude and duration of beta-receptor blockade. In placebo-controlled clinical trials, the effects of infusion of esmolol on the sympathetically mediated hemodynamic responses to stressful events during the perioperative period were evaluated in patients scheduled for surgical procedures under general anesthesia. In patients undergoing either noncardiac or cardiac surgical procedures, esmolol was effective in attenuating tachycardia that is normally seen during induction of anesthesia, laryngoscopy and endotracheal intubation, or sternotomy and aortic dissection by reducing the hemodynamic stress on the heart with negligible adverse effects. This much-desired cardioprotective effect of esmolol will be of special value to patients with coronary artery disease and patients with an unstable cardiovascular status who are undergoing major surgical procedures with general anesthesia.

Adrenergic beta-Antagonists↗
PubMed1986

Mechanism of counteraction of aflatoxin toxicity by thymine and folic acid in Bacillus megaterium.

Thymine and cytosine as well as the intermediates in pyrimidine biosynthetic pathway dihydroorotic acid, orotic acid, carbamyl aspartate and 5'-uridine monophosphate and folic acid, was synergistic. 2-14C-Thymine, 6-14C-orotic acid and 14C-formate but not 2-14C-uracil, were incorporated into DNA more in the presence of aflatoxin. These findings indicated that aflatoxin inhibited the pyrimidine base synthesis which could be overcome to a great extent by the addition of thymine and folic acid to aflatoxin-treated cells.

Aflatoxin B1↗
PubMed1986

Antiarrhythmic drugs and the modulation of autonomic control of heart rate in rabbits.

A model of the components of autonomic control of heart rate was developed and used for the evaluation of quantitative contribution of sympathetic and vagal tone to cardiac function. In conscious rabbits, sequential inhibition of muscarinic and beta receptors was produced and the relative contributions of vagal and sympathetic tone were characterized. Based on the model, the magnitude of presynaptic interaction between the vagal and sympathetic nerve endings was evaluated. From data in the literature, similar analysis of the control of heart rate was performed for the rat, dog, and human subject and compared with that of the rabbit. The results show that the resting rabbit heart is under less vagal tone than sympathetic tone as compared with other species. The effects of acute administration of amiodarone on the sympathetic and parasympathetic control of heart rate as well as intrinsic heart rate were investigated. Amiodarone decreased the heart rate, which resulted from a direct effect on the sinoatrial (SA) node. In addition, it attenuated the vagal as well as the sympathetic effects on the SA node. The effect on vagal component was greater. Further, the effects of other antiarrhythmic drugs on the electrocardiographic PP and PR intervals were studied. The usefulness of this model for the analysis of the effects of antiarrhythmic drugs is presented.

Adenosine↗
PubMed1984

Coexisting cervical and lumbar spinal stenosis: diagnosis and management.

An attempt has been made to identify and manage patients symptomatic from both cervical and lumbar spinal stenosis. The order of operative intervention was related to the degree of myelopathy and radiculopathy. Patients requiring cervical surgery first had absolute stenosis with a spinal canal equal to or less than 10 mm in anteroposterior diameter. Those requiring lumbar surgery first presented with stenosis and a canal between 11 and 13 mm in depth. In the latter group, patients presented with radiculopathy in their upper and lower extremities. A significant portion (50%) had intermittent neurogenic claudication (INC). Motor and sensory changes were severe in those with absolute as compared to relative stenosis. After cervical laminectomy, myelopathy improved or stabilized, and the subsequent lumbar decompression could be completed with less risk. Cervical cord decompression often resulted in improvement in lumbar symptoms with resolution of pain, spasticity, and sensory deficits of myelopathic origin. However, latent symptoms of INC caused by lumbar stenosis were not affected by cervial decompression and increased in severity. Electrodiagnostic studies were helpful in that somatosensory evoked potentials showed conduction delays in the cervical cord in patients with significant disease. The identification of motor neuron disease and peripheral neuropathies was essential. The surgical management included extensive, multiple level laminectomy, unroofing of the lateral recesses, and foraminotomy. Neurolysis and untethering of the spinal cord was essential. Significant improvement was shown by 90% of these patients.

Aged↗
PubMed1984

Diminished sympathetic responsiveness in nephrectomized rats-role of the renin angiotensin system.

Experiments were conducted in pithed Wistar rats to assess the effects of nephrectomy on the responsiveness of the cardiovascular system to sympathetic neurohumoral stimuli. Blood pressure and heart rate increases produced in response to stimulation of the spinal sympathetic outflow and to norepinephrine were compared in nephrectomized (NXR) and sham operated animals (SOR). Both the blood pressure (BP) and heart rate (HR) increases to nerve stimulation were markedly attenuated in the NXR, however, only the reduction in BP responses could be attributed to the absence of a functional renin angiotensin system. Infusion of angiotensin II (10 ng/kg/min) in NXR enhanced the neurally mediated increments in BP to the extent that the responses were not different from SOR. Angiotensin II administration also enhanced BP responses in SOR but to a lesser extent than in NXR. HR responses were not altered by angiotensin in NXR or SOR. Blockade of the renin angiotensin system in SOR with the converting enzyme inhibitor, captopril, reduced BP responses to the same level as NXR. In contrast, HR increments were not altered by captopril. BP but not HR increments to norepinephrine were significantly reduced in NXR. Infusion of angiotensin II restored the BP responses to a level equal to SOR; HR responses were not affected. In addition, captopril reduced the norepinephrine responses of SOR but not NXR. Thus the results of the present study indicate that endogenously formed angiotensin facilitates sympathetically mediated vasoconstrictor activity but does not influence heart rate responses. Therefore, the attenuation of neurally elicited increases in HR observed in NXR does not appear to be acutely related to reduced levels of angiotensin II.

Angiotensin II↗
PubMed1983

Cardiovascular pharmacology of ASL-8052, an ultra-short acting beta blocker.

ASL-8052, a novel ultra-short acting beta receptor blocking agent, was infused i.v. and its cardiovascular effects were investigated in conscious, as well as anesthetized rabbits. On i.v. infusion, its effects reached a steady state within 6 min and on termination of infusion, complete recovery occurred within 20 min. In conscious rabbits it inhibited isoproterenol-induced tachycardia and hypotension. There was more pronounced inhibition of the cardioaccelerator effects of isoproterenol than its hypotensive effects. ASL-8052 produced dose dependent bradycardia in conscious rabbits which was more marked in rabbits pretreated with atropine methyl nitrate. When infused in larger doses, a significant decrease in mean arterial pressure was seen in conscious as well as anesthetized rabbits. This hypotensive effect was not blocked by prior beta receptor blockade with propranolol. ASL-8052-induced hypotension was found to be due to a significant decrease in total peripheral resistance. It also produced vasodilation in the mesenteric vascular bed. The role of the liver in the clearance of ASL-8052 was investigated. When infused into the portal vein, the response to ASL-8052 was markedly attenuated, while an equivalent dose infused into the femoral vein produced a significant level of beta receptor blockade. These results suggest that ASL-8052 is an ultra-short acting beta receptor blocking agent with vasodilator effects in rabbits. While the liver may play a significant role in the clearance of ASL-8052 from circulation, the role of extra-hepatic mechanisms in the rapid decay of its pharmacological effects remains to be investigated.

Adrenergic beta-Antagonists↗