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Biomedical subjects

S P Verma

Publications and source records attributed to S P Verma.

At least 19 recordsLinked to original sources
PubMed1992

Hexachlorocyclohexane pesticides reduce survival and alter plasma membrane structure of Chinese hamster V79 cells.

We studied the cytotoxic effects of alpha-, beta-, gamma-, and delta-hexachlorocyclohexanes (HCCH) on the survival of Chinese hamster V79 cells using clonogenic assays. Lethal dose yielding 50% cell survival (LD50) suggests the following order of cytotoxicity: delta-(+)gamma-HCCH (LD50 4 micrograms/ml) (1:1, w/w, mixture) > delta-HCCH (LD50 6 micrograms/ml) > gamma-HCCH (LD50 13 micrograms/ml) > alpha-HCCH (LD50 approx. 35 micrograms/ml) >> beta-HCCH. Structural changes in plasma membranes prepared from HCCH-treated V79 cells at dose yielding 10% cell survival (LD10) were analyzed using Raman spectroscopy. Raman spectra of plasma membranes show bands at 2850, 2880-2890, and 2935 cm-1 in the C-H stretching region. The plot of the ratio (I2880-2890/I2850) vs temperature for control plasma membranes shows two transitions between -5 and 5 degrees C and between 12 and 20 degrees C. Plasma membranes prepared from gamma- and delta-HCCH-treated Chinese hamster V79 cells show single transitions between -4 and 11 degrees C and between -2 and 11 degrees C, respectively. These changes in the thermal transition properties suggest that both gamma- and delta-HCCH alter lipid and lipid-protein phases of the plasma membrane of V79 cells. Raman analysis of the amide I and amide III region spectra further suggest that delta-HCCH also alters the secondary structure and the environment of highly amidated segments of plasma membrane proteins. We suggest that the primary action of biologically active HCCH isomers is to disrupt the organization of the plasma membrane and that may affect cell viability.

Animals↗
PubMed1992

Cardiac resuscitation with percutaneous cardiopulmonary support.

Percutaneous cardiopulmonary support (CPS) was initiated in 9 patients to provide haemodynamic stability after failure of conventional resuscitation. 4 patients were in cardiogenic shock and 4 remained in asystole, with 1 in resistant ventricular fibrillation, after cardiac arrest. During CPS for those in cardiogenic shock, the mean intra-arterial pressures ranged from 65 to 100 mm Hg (mean 84), at flow rates of between 3 to 5 l/min (mean 3.9). 2 patients underwent technically successful coronary angioplasty. No patient in this group survived. In the cardiac arrest group, acceptable mean intra-arterial blood pressures were achieved (mean 95, range 90-100 mm Hg) at flow rates of between 2 to 3 l/min (mean 2.6). All 5 subjects underwent technically successful coronary angioplasty whilst on CPS. 4 survived. 2 were alive and well at 12 months follow-up, 1 of whom had returned to work; the third is alive and well at 4 months.

Aged↗
PubMed1992

Modulation of inotropic therapy by venodilation in acute heart failure: a randomised comparison of four inotropic agents, alone and combined with isosorbide dinitrate.

The effects of four inotropic agents with differing ancillary properties [a cardiac glycoside (digoxin), a combined alpha- and beta-adrenergic agonist (dobutamine), a beta-adrenergic agonist (prenalterol), and a phosphodiesterase inhibitor (amrinone)] alone and with subsequent addition of isosorbide dinitrate were compared in 48 consecutive acute myocardial infarction patients with radiographic and haemodynamic (pulmonary artery occluded pressure greater than 18 mm Hg) left ventricular failure. All agents with the exception of dobutamine reduced the elevated left heart filling pressure; only digoxin and dobutamine augmented the cardiac stroke volume index. All drugs except digoxin reduced the SVRI; an arteriolar constrictor response was evident 60 min after digoxin and a tachycardia resulted after combined alpha- and beta- and beta-adrenergic stimulations (dobutamine and prenalterol, respectively). The addition of isosorbide dinitrate reversed the inotrope-induced elevations of systemic arterial pressure and resulted in additional reductions in left heart filling pressure. These data suggest that, in the absence of substantial venodilator properties in an inotropic compound, reduction in elevated left heart filling pressure is not achieved with inotropic therapy alone in acute left ventricular failure and combining a venodilator may be haemodynamically advantageous.

Adult↗
PubMed1992

Vasodilator therapy for acute heart failure: haemodynamic comparison of hydralazine/isosorbide, alpha-adrenoceptor blockade, and angiotensin-converting enzyme inhibition.

Haemodynamic comparison of three vasodilation regimens [intravenous (i.v.) hydralazine and isosorbide dinitrate (ISDN) combined, i.v. doxazosin, and i.v. enalaprilat] was undertaken in 36 patients with acute left ventricular (LV) failure due to recent myocardial infarction. Each regimen achieved similar reductions in pulmonary artery occluded pressure (PAOP, preload) and systemic arterial pressures (afterload), with increased cardiac and stroke volume (SV) indexes (p less than 0.01). Only the hydralazine and isosorbide combination induced resting tachycardia. Balanced vasodilatation after selective alpha-adrenoceptor blockade (doxazosin) and angiotensin-converting enzyme (ACE) inhibition (enalaprilat) without increase in heart rate (HR) suggests that these therapies may have definite haemodynamic advantages over the hydralazine/ISDN combination.

Adrenergic alpha-Antagonists↗
PubMed1991

Low levels of the pesticide, delta-hexachlorocyclohexane, lyses human erythrocytes and alters the organization of membrane lipids and proteins as revealed by Raman spectroscopy.

We studied the nature of the interaction of delta-hexachlorocyclohexane (delta-HCCH), a pesticide having a stereoisomeric structure similar to inositol, with red blood cells. Cell survival data, measured as percent of hemoglobin released by delta-HCCH, show that the cell lysis increases with post exposure time. delta-HCCH at 55-60 micrograms/ml causes about 70% cell lysis after 24 h of exposure. The nature of interaction of delta-HCCH with membrane components was evaluated by studying the thermotropic transitions and protein structure of ghosts using Raman spectroscopy. Control ghosts show transitions with onset/completion temperatures 30 degrees C/38 degrees C (high temperature transition) and 3 degrees C/10 degrees C (middle temperature transition) when monitored by the I2935/I2850 ratio. The interaction of delta-HCCH drastically broadens the high temperature transition and shifts it to the temperature range of 10-29 degrees C. The plots of (I2880-90/I2850) vs. temperature show two transitions for control ghosts, one extending from -10 degrees C to 3 degrees C (lower temperature transition) and the other from about 7 degrees C to about 15 degrees C (middle temperature transition). Ghosts lysed with delta-HCCH shows only a single and a very broad transition in the range of about -3 degrees C to about 15 degrees C. These changes in the thermal transition properties suggest that delta-HCCH alters lipid and lipid-protein phases of erythrocyte membranes. The comparison of Raman spectra in the amide I and III regions of erythrocyte ghosts and purified band 3 with several amidated compounds reveals that cytoskeleton proteins contain highly amidated residues (probably glutamine and asparagine). The interaction of delta-HCCH with erythrocytes drastically alters the environment of these amidated residues indicating the involvement of cytoskeleton proteins. We conclude that the interaction of delta-HCCH with red blood cells disrupt membrane structure and change the environment of cytoskeleton proteins that could cause cell lysis.

Amides↗
PubMed1991

Hemodynamic interactions of a new beta blocker, celiprolol, with nifedipine in angina pectoris.

The hemodynamic consequences of blockade at both beta-adrenoceptors and slow calcium channels is of therapeutic importance for patients with angina pectoris. The hemodynamic interaction of a new cardioselective beta blocker, celiprolol, and nifedipine was examined in an acute hemodynamic study using three prospectively matched groups with angiographically confirmed coronary artery disease (n = 10/group). Patients were randomly allocated to intravenous celiprolol (8 mg), sublingual nifedipine (20 mg), or their combination. Rest and exercise (supine bicycle) hemodynamics were determined before and following each therapy. At rest, celiprolol did not alter pumping function; nifedipine reduced diastolic blood pressure and systemic vascular resistance index (SVRI), with a small increase in heart rate. Combination therapy reduced systemic arterial pressure and SVRI; heart rate and cardiac stroke volume index increased. During exercise celiprolol tended to reduce heart rate and cardiac index; nifedipine reduced exercise SVR and cardiac stroke work indices. Combination therapy reduced all components of blood pressure; cardiac stroke work and SVR indices fell. These hemodynamic data suggest that beta blockade with celiprolol may result in a slight depression of cardiac pumping during exercise; however, such effects are offset by the vasodilating actions of nifedipine (reflex sympathetic action offsetting cardiodepression). Thus the acute hemodynamic effects of this combination were seemingly safe in these patients; the longer term effects during maintained therapy should be further assessed.

Adrenergic beta-Antagonists↗
PubMed1991

Pharmacokinetics and urinary excretion of gentamicin in Bubalus bubalis calves following intramuscular administration.

The pharmacokinetics and urinary excretion of gentamicin was studied in buffalo calves after a single intramuscular administration (10 mg kg-1). Kinetic determinants were calculated by using a two compartment open model. The absorption (t1/2Ka) and biological half lives (t1/2 beta) were calculated to be 0.43 +/- 0.08 and 3.79 +/- 0.23 h, respectively. The value of the apparent volume of distribution (VdB) was found to be 0.38 +/- 0.07 litre kg-1. The satisfactory intramuscular dosage regimen of gentamicin for buffalo calves would be 3.23 mg kg-1 as priming dose and 2.88 mg kg-1 as maintenance dose to be repeated at 12 hour intervals to achieve and maintain the therapeutic plasma levels within safe limits. Urinary excretion of gentamicin was very rapid during the first 12 hours as 48.07 +/- 1.39 per cent of the total administered dose was excreted unchanged during this period.

Absorption↗
PubMed1991

Post-epidemic serological survey for JE virus antibodies in south Arcot district (Tamil Nadu).

Following an extensive epidemic of Japanese encephalitis (JE) in 1981, a serological survey was carried out in the South Arcot district of Tamil Nadu in April 1982. Serum specimens were obtained from 10 villages with serologically proven infections and 6 villages with no reported case of encephalitis during the 1981 epidemic. The serum specimens tested for haemagglutination inhibition, complement fixing and neutralizing antibodies, showed a high prevalence of JE (49.17%), West Nile (40.78%) and dengue (18.14%) viruses with predominance of JE. The prevalence did not differ between the villages with or without Japanese encephalities. There was also no difference between the family members and neighbours.

Antibodies, Viral↗
PubMed1991

Structural changes in plasma membranes prepared from irradiated Chinese hamster V79 cells as revealed by Raman spectroscopy.

The effect of gamma irradiation on the integrity of plasma membranes isolated from Chinese hamster V79 cells was investigated by Raman spectroscopy. Plasma membranes of control V79 cells show transitions between (-) 10 and 5 degrees C (low-temperature transition), 10 and 22 degrees C (middle-temperature transition), and 32 and 40 degrees C (high-temperature transition). Irradiation (5 Gy) alters these transitions markedly. First, the low-temperature transition shifts to higher temperature (onset and completion temperatures 4 and 14 degrees C). Second, the middle-temperature transition shifts up to the range of about 20-32 degrees C, but the width remains unchanged. Third, the higher temperature transition broadens markedly and shifts to the range of about 15-40 degrees C. Protein secondary structure as determined by least-squares analysis of the amide I bands shows 36% total helix, 55% total beta-strand, and 9% turn plus undefined for control plasma membrane proteins. Plasma membrane proteins of irradiated V79 cells show an increase in total helix (40 and 45% at 5 and 10 Gy, respectively) and a decrease in the total beta-strand (48 and 44% at 5 and 10 Gy, respectively) structures. The qualitative analysis of the Raman features of plasma membranes and model compounds in the 1600 cm-1 region, assigned to tyrosine groups, revealed that irradiation alters the microenvironment of these groups. We conclude that the radiation dose used in the survival range of Chinese hamster V79 cells can cause damage to plasma membrane proteins without detectable lipid peroxidation, and that the altered proteins react differently with lipids, yielding a shift in the thermal transition properties.

Animals↗
PubMed1990

Organic pesticides modify lipid-lipid and lipid-protein domains in model membranes. A laser Raman study.

The effect of hexachlorocyclohexane (all isomers) on the thermal transition properties of phospholipid liposomes was determined by Raman spectroscopy. Raman spectra of liposomes with and without the presence of hexachlorocyclohexanes were recorded in the C-H stretching region which shows three major bands around 2850, 2880 and 2930 cm-1. Thermal transition properties were estimated from plots of I2880/I2850 and or I2930/I2850 vs. temperature, where I represents the intensity of the respective band. Our data on phospholipid liposomes reveal that delta- and gamma-hexachlorocyclohexanes drastically reduce and broaden the main thermal transitions of phospholipids at toxic level concentrations. These effects are more pronounced in liposomes containing 18 or more carbon atom long acyl chains. Alpha- and beta-isomers at similar concentrations show a minimum effect on the thermal transition properties of phospholipids. Raman analysis of phospholipid liposomes containing melittin, interestingly, reveal that the delta-isomer unlike the gamma-isomer strongly alters the transition properties of boundary lipids. These data suggest that the effect of hexachlorocyclohexanes on the thermal transition properties of membranes is stereo specific and that the delta-isomer preferably disrupts the lipid-protein domains. Results are explained on the basis of the dynamic flexibility owing to the equatorial and axial chlorine atoms of various hexachlorocyclohexane isomers.

Chemical Phenomena↗
PubMed1990

An exercise hemodynamic comparison of verapamil, diltiazem, and amlodipine in coronary artery disease.

A prospective, randomized study compared the effects of equivalent intravenous doses of three slow calcium-channel blockers (verapamil, diltiazem, and amlodipine) on rest and exercise haemodynamics in 30 ischemic heart disease patients. Following a stable control period during which rest and exercise (supine bicycle) hemodynamics were assessed, equivalent hypotensive doses of each compound were administered over 20 minutes and rest/exercise parameters were assessed 10 minutes later. At rest all agents similarly reduced systemic blood pressure; the fall in systemic vascular resistance and the increase in cardiac indices was ranked: amlodipine greater than diltiazem greater than verapamil. The heart rate increase for amlodopine differed from verapamil and diltiazem (+19.4% vs. +1.5% vs. -7%; p less than 0.01). On exercise, similarly greater falls in the systemic vascular resistance index followed amlodipine, compared with verapamil and diltiazem (p less than 0.05). Only amlodipine significantly reduced the exercise pulmonary artery occlusion pressure (PAOP). Exercise cardiac stroke volume improved after diltiazem and amlodipine. In terms of cardiac performance, both amlodipine and diltiazem produced an improvement, whereas verapamil depressed cardiac pumping activity. Thus, hemodynamic differences between slow-calcium-channel blocking drugs may be demonstrated in humans. These differences would be compatible with a predominant peripheral vascular site of action for amlodipine, in contrast with mixed cardiac and peripheral sites for diltiazem and verapamil.

Amlodipine↗
PubMed1990

How does posture influence the haemodynamic assessment of a cardiovascular drug? Experience with nicardipine.

The extent to which posture altered the haemodynamic response to slow calcium channel blocker nicardipine was evaluated in 22 male patients with angiographically confirmed coronary artery disease. Patients were randomly allocated to supine or upright posture and an otherwise identical protocol performed in each group. At rest, following a control saline period, four doses of the drug (log cumulative dosage: 1.25, 2.5, 5.0, and 10.0 mg) were administered by i.v. infusion over a total period of 40 min; haemodynamic indices were recorded during the 3-5 min following each 5 min infusion. The exercise effects of the drug, in each posture, were determined by comparison of a control predrug exercise with observations at the same workload following the maximal cumulative dose. Nicardipine reduced resting mean blood pressure (MBP) and systemic vascular resistance index (SVRI) in both postures, the decrease being more pronounced when upright (MBP, -12%, -18%; p less than 0.01: SVRI, -30%, -46%; p less than 0.01). The increases in cardiac index (CI) and stroke volume index (SVI) were higher when upright (29 and 54% vs. 10 and 27%; p less than 0.01). Pulmonary artery occluded pressure (PAOP) increased by 29% when upright, without change when supine. On exercise, the effects for HR, MBP, CI, SI, and SVRI responses were independent of posture; however, a qualitative difference was apparent for PAOP (-17% vs. +14%; p less than 0.05). Thus, although the actions of nicardipine were qualitatively similar, quantitative differences related to posture were confirmed. These differences appeared to relate to posture-related baseline haemodynamic differences between the groups but with similar postnicardipine absolute values.

Adult↗
PubMed1990

Haemodynamic and radionuclide effects of amlodipine in coronary artery disease.

1. The haemodynamic and radionuclide effects of a new long-acting slow-calcium channel blocking agent, amlodipine, were evaluated in 32 patients with coronary artery disease. 2. Haemodynamic measurements in 24 patients were made at rest and 10 to 15 min after 20 mg i.v. amlodipine. Amlodipine significantly reduced systemic arterial blood pressure and vascular resistance index with an increased heart rate and augmented cardiac index. Cardiac stroke volume index rose and stroke work fell without change in pulmonary artery occluded pressure (PAOP). 3. The exercise effects were determined by comparison of measurements during 4 min of supine bicycle exercise at a fixed workload before and after drug treatment. During dynamic exercise, amlodipine reduced systemic arterial pressure and vascular resistance index. Exercise cardiac index, stroke volume index and heart rate were higher. The left ventricular filling pressure was significantly reduced. 4. Radionuclide parameters were studied in 16 patients at rest and on exercise; ejection fraction was unaltered following amlodipine. 5. Pre-therapy haemodynamic values correlated with response following amlodipine for resting mean blood pressure, systemic vascular resistance and exercise PAOP. 6. Thus, the immediate impact of amlodipine in stable coronary artery disease was to reduce left ventricular afterload and thereby improve cardiac pumping performance.

Adult↗
PubMed1990

Pharmacodynamic monitoring during acute intervention in ischaemic heart disease using a new echo-Doppler device.

1. We have utilised a new non-imaging echo-Doppler cardiac output device, using the principle of attenuated compensated volume flow (ACVF), to assess the cardiovascular effects of atenolol and buccal nitroglycerin (NTG) in a placebo-controlled study of 30 patients with coronary disease. 2. Atenolol (4 mg i.v.) reduced heart rate, cardiac output and time-averaged mean aortic velocity (P less than 0.01) and increased systemic vascular resistance (P less than 0.01). 3. Buccal NTG (5 mg) reduced systemic mean arterial pressure (P less than 0.01), cardiac stroke volume (P less than 0.05) and stroke length (P less than 0.01). 4. Thus although both drugs reduced time-averaged aortic velocity (an index of cardiac performance), the concomitant reduction in cardiac stroke length and tachycardia suggested sub-optimal cardiac filling for buccal NTG, whereas for atenolol (with the associated increased systemic vascular resistance but unchanged stroke length) attenuation of sympathetic stimulation at cardiac beta-adrenoceptors. 5. The ACVF method of cardiovascular monitoring should prove useful in human pharmacodynamic studies.

Adult↗
PubMed1990

Haemodynamic dose-response effects of UK-52,046 in ischaemic disease with or without impaired left ventricular function.

1. The haemodynamic effects of a new cardioselective postsynaptic alpha 1-adrenoceptor antagonist UK-52,046, were evaluated in 25 patients with stable coronary disease, with or without impaired left ventricular function. At rest the haemodynamic effects to two dose-response regimens were determined. In an initial eight patients 0.125, 0.125 and 0.25 micrograms kg-1 were administered peripherally at 15 min intervals; the haemodynamic measurements were determined between 10 to 15 min after each dose. In a further 17 patients, the dose regimen was doubled yielding a cumulative dose-regimen of 0.25, 0.5 and 1.0 micrograms kg-1. The exercise effects were determined by comparison of measurements during 4 min of supine sub-maximal bicycle exercise at a fixed workload before and after drug treatment. 2. At rest, the lower dose regimen of UK-52,046 significantly reduced systemic mean arterial blood pressure (-5 mm Hg; P less than 0.05) and increased cardiac index (+0.2 l min-1 m-2, P less than 0.01). The higher dose regimen of UK-52,046 reduced systemic mean arterial blood pressure (-7 mm Hg; P less than 0.01), pulmonary artery occluded pressure (PAOP) (-2 mm Hg, P less than 0.01) and vascular resistance index (-314 dyn s cm-5 m2; P less than 0.05) with an increase in heart rate (+7%, P less than 0.05) and cardiac index (+0.2 l min-1 m-2, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗