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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 109 records · Page 6Linked to original sources
PubMed1996

Oxidative stress as a mechanism of cardiac failure in chronic volume overload in canine model.

We investigated the effects of chronic volume overload in the absence or presence of vitamin E supplements on the cardiac function and contractility, cardiac malondialdehyde (MDA)--a lipid peroxidation product--cardiac antioxidant enzyme activity and antioxidant reserve in canine model. The dogs were divided into three groups of seven dogs each: group I, control; group II, mitral regurgitation (MR) of 4 months duration; and group III, MR of 4 months duration receiving vitamin E (40 U/kg/daily) orally. MR was created by detaching two or more chordae tendinae to raise left atrial pressure to 2.5 to three times normal. MR produced a decrease in the index of myocardial contractility with little change in myocardial function. Decrease in myocardial (left and right ventricles) contractility was associated with an increase in cardiac MDA, and a decrease in cardiac antioxidant reserve and antioxidant enzyme activity. Prevention of volume overload-induced decrease in myocardial contractility by vitamin E was associated with a decrease in cardiac MDA and an increase in cardiac antioxidant reserve and glutathione peroxidase activity towards control levels. Superoxide dismutase and catalase activity remained depressed in vitamin E-treated group. The results indicate that chronic volume overload decreases the contractility of both right and left ventricles and is associated with oxidative stress in both ventricles. These results support the hypothesis that oxygen free radicals are involved in the chronic volume overload-induced cardiac depression.

Animals↗
PubMed1996

Hydroxyl radical--a mediator of acetylcholine-induced vascular relaxation.

It is well known that acetylcholine (Ach)-induced vasodilation is mediated through the release of the endothelium-derived relaxing factor (EDRF), nitric oxide (NO.). It has been suggested that NO interacts with superoxide anion (O2-) to generate peroxynitrite which at physiological pH gives rise to peroxynitrous acid than rapidly decomposes to hydroxyl radical (.OH) and nitrogen dioxide, .OH relaxes isolated aorta. It was hypothesized that Ach-induced vascular relaxation is mediated by .OH derived from interaction of NO and O2-. To test this hypothesis we investigated the effect of Ach on norepinephrine (NE)-precontracted isolated rabbit aortic preparations in the absence or presence of scavengers of O2- [superoxide dismutase (SOD)] and of .OH [dimethylthiourea (DMTU) or mannitol]. .OH and Ach produced relaxation of NE-precontracted preparations in a concentration-dependent manner. Relaxation produced by .OH generating system was prevented by mannitol, a .OH scavenger suggesting that relaxation is due to .OH. SOD. DMTU, mannitol or combination of SOD and DMTU markedly reduced the Ach-induced relaxation. Glyburide (an ATP-sensitive K+ channel blocker) was ineffective in blocking the Ach-induced remaining relaxation in the presence of SOD and DMTU. These results suggest that .OH formed from interaction of O2- and NO. is the mediator of Ach-induced vascular relaxation. Thus while EDRF is NO. its mechanism of action involves .OH.

Acetylcholine↗
PubMed1996

Effects of probucol on hypercholesterolemia-induced changes in antioxidant enzymes.

Effects of high cholesterol diet (0.5% and 1%) on the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px)] in the aortic tissue of rabbits were investigated in the absence or presence of probucol (0.5 gm/kg daily, orally). Five groups of ten rabbits each were studied. Group I, regular rabbit chow diet; Group II, chow + 0.5% cholesterol; Group III, chow + 0.5% cholesterol+probucol; Group IV, chow + 1% cholesterol and Group V, chow + 1% cholesterol+probucol. The aorta was removed at the end of 4 months for measurement of the antioxidant enzymes. An increase in activity of aortic antioxidant enzymes was noted in cholesterol-fed rabbits (Groups II and IV), being similar for SOD and catalase but higher for GSH-Px in Group IV as compared to Group II. Probucol was ineffective in altering this cholesterol-induced increase in enzyme activity except in Group III where it increased the activity of GSH-Px. These results suggest that aortic antioxidant enzymes are affected in hypercholesterolemia and that probucol is ineffective in altering the aortic antioxidant enzyme activity except GSH-Px activity which increased in 0.5% cholesterol-fed rabbits. The protective effects of probucol against hypercholesterolemic atherosclerosis may be partly due to an increase in the GSH-Px activity at low levels of hypercholesterolemia. At higher levels of hypercholesterolemia, the protective effects of probucol could be due to its antioxidant activity.

Animals↗
PubMed1996

Role of polymorphonuclear leukocytes in cardiovascular depression and cellular injury in hemorrhagic shock and reinfusion.

We investigated the role of polymorphonuclear leukocytes (PMNLs) in cardiac depression and cytotoxicity during hemorrhagic shock and reinfusion. The dogs were assigned to four groups: I (sham), 4 h duration; II, 2 h of shock followed by reinfusion for 2 h; III, shock and reinfusion in neutrophils depleted with immune serum; IV, same as III but pretreated with nonimmune serum. Cardiac function and contractility were depressed during shock while plasma creatine kinase (CK), and CK-MB increased. Reinfusion tended to return hemodynamic parameters towards control values while oxygen free radical producing activity of PMNLs, plasma CK, and CK-MB increased further. Cardiac malondialdehyde (lipid peroxidation product) and superoxide dismutase activity were higher while left ventricular chemiluminescence was lower in group II as compared to group I. Despite the increase in the antioxidant reserve and antioxidant enzymes, there was oxidative damage. PMNL depletion attenuated the deleterious effects of shock and reinfusion on the hemodynamic and biochemical parameters. The changes in group IV were similar to those in group II. These results suggest that PMNLs may partly be involved in the deterioration of cardiac function, and contractility and cellular injury during hemorrhagic shock and reinfusion.

Animals↗
PubMed1996

The Glasgow Coma Scale: a critical appraisal of its clinimetric properties.

The Glasgow Coma Scale is a commonly used instrument in clinical practice. This article examines the published evidence to assess whether the scale possesses the requisite clinimetric properties. Articles describing and using the scale were located through a MEDLINE search. The clinimetric properties of the scale were appraised using the methodological principles of sensibility, reliability, validity, and responsiveness. The scale has a good sensibility and reliability (intraclass correlation coefficient, 0.8 to 1 for trained users). It has a well-established cross-sectional construct validity. Its predictive validity in traumatic coma, when combined with age and brainstem reflexes, is good in the generating sample (sensitivity, 79 to 97%; specificity, 84-97%) but has not been tested in an external validation sample. Its longitudinal construct validity has not been studied adequately. Thus, the scale is an established discriminative instrument but its validity as a predictive and an evaluative instrument has not yet been studied adequately.

Coma↗
PubMed1996

Time course study of oxidative stress in aorta and heart of diabetic rat.

1. Oxygen free radicals have been suggested to be a contributory factor in complications of diabetes mellitus. In the present study, we investigated the lipid peroxide level [thiobarbituric acid-reactive substances (TBARS)] and activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) in aorta, heart and blood of control and streptozotocin-induced diabetic rats at various stages of development of diabetes (0 to 6 weeks). 2. There was no change in the TBARS levels of aorta, heart and blood in the control group. A significant (P < 0.05) increase in TBARS levels of aorta, heart and blood was observed in the diabetic group. 3. There were no significant changes in the activities of superoxide dismutase, catalase and glutathione peroxidase in the aorta, heart and blood of control rats at all time intervals. In the diabetic group, there was a significant (P < 0.05) increase in the activity of superoxide dismutase and glutathione peroxidase in aorta from the fourth week onwards while the activity of catalase increased at all time intervals. In the heart of diabetic rats, the activity of total superoxide dismutase and Cu-Zn-superoxide dismutase increased significantly (P < 0.05) from the second week onwards while activity of Mn-superoxide dismutase decreased at the fourth week and increased at the sixth week. The activity of catalase and glutathione peroxidase increased significantly (P < 0.05) at all time intervals. In the blood, the activity of superoxide dismutase and glutathione peroxidase increased from the third week while catalase activity increased from the fourth week. 4. The present findings suggest that oxidative stress starts at early onset of diabetes mellitus and increases progressively.

Animals↗
PubMed1996

QT dispersion and RR variations on 12-lead ECGs in patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy.

Increased QT dispersion, which has been proposed as a marker of ventricular repolarization inhomogeneity, may predispose to ventricular arrhythmias. Data on QT dispersion in patients with congestive heart failure are scarce. In this study, conventional 12-lead ECGs were recorded in 135 consecutive patients with congestive heart failure secondary to idiopathic dilated cardiomyopathy. Seventy-five patients were excluded from QT interval assessments due to one or more of the following reasons: (1) low amplitude of the T wave (n = 3), (2) atrial fibrillation (n = 26) and (3) bundle branch block (n = 46). QT dispersion was calculated as (1) QT-range: the difference between the maximum and minimum QT intervals on any of the 12 leads and (2) QT-SD: the standard deviation of the QT interval in all the 12 leads. RR intervals were measured in leads II, aVL, V2 and V5. QT-SD (20.85 +/- 5.00 ms) was significantly (r = 0.8997, P < 0.001) related to QT-range (65.65 +/- 15.77 ms), but not to the QT interval. Neither QT-range nor QT-SD was significantly related to age, left ventricular dimensions, left ventricular end diastolic pressure, left ventricular ejection fraction or left ventricular wall thickness. There was no significant difference in QT dispersion between survivors and those who died (n = 8) or were transplanted (n = 9) during 34 +/- 23 month follow-up. No significant difference in QT dispersion was observed between patients with and without ventricular tachycardia (> or = three consecutive beats) detected on 24-h Holter ECGs. RR interval variation was significantly lower in patients who died compared with survivors (standard deviation: 10.37 +/- 3.61 vs 36.02 +/- 35.03 ms, P < 0.001; coefficient of variance: 1.87 +/- 0.7% vs 4.50 +/- 4.9%, P = 0.001). This was also true in patients with bundle branch block. These observations suggest that QT dispersion in idiopathic dilated cardiomyopathy is not significantly related to either QT interval or cardiac size and function and does not predict death. The application of QT dispersion assessment is limited by the commonly encountered atrial fibrillation and bundle branch block in this patient population. However, reduced RR variation on standard 12-lead ECGs has important prognostic implications in these patients.

Adult↗
PubMed1996

Chest pain during daily life in patients with hypertrophic cardiomyopathy: an ambulatory electrocardiographic study.

Patients with hypertrophic cardiomyopathy frequently complain of chest pain during daily activities. ST-segment depression is described in association with sudden death and pacing, but its prevalence during ambulatory electrocardiographic monitoring is unknown. The aim of this study was to determine the relation of ambulatory ST-segment depression to clinical characteristics, risk factors for sudden death and thallium-201 perfusion in patients with hypertrophic cardiomyopathy. Continuous 48 h ambulatory electrocardiographic monitoring was performed in 113 patients (age 38 +/- 14 years) with hypertrophic cardiomyopathy. Ninety-four (83%) recordings were suitable for ST-segment analysis. A total of 109 episodes of ST-segment depression (> or = 1 mm from baseline) were recorded in 25 (27%) patients (mean 4 +/- 5). In patients < or = 30 years of age (but not > 30) there was an association between ST-segment depression and a history of exertional chest pain (seven of 12 vs one of 20; P = 0.001), and dyspnoea NYHA class II/III (seven of 15 vs one of 17; P = 0.008). There was no association between ST-segment depression and risk markers for sudden death, i.e. family history of sudden death, syncope and non-sustained ventricular tachycardia, in any group. Reversible thallium-201 defects occurred in 27 (29%) of the 94 patients with analysed recordings but were not associated with symptoms, risk factors for sudden death or ambulatory ST-segment depression. In young patients with hypertrophic cardiomyopathy, ischaemia-like ST-segment depression is common and is associated with a history of typical angina and dyspnoea. Reversible thallium-201 perfusion defects are associated with neither symptomatic status nor ambulatory ST-segment depression.

Activities of Daily Living↗
PubMed1996

Priapism following ingestion of papaverine tablets.

A case of priapism following oral intake of papaverine hydrochloride (300 mg) is reported. The priapism persisted after coitus. It resisted conservative treatment, but responded to aspiration of the corpora cavernosa and irrigation with phenylephrine solution. We found no earlier report of priapism induced by oral papaverine. The possible therapeutic role of oral papaverine in impotence merits study.

Administration, Oral↗
PubMed1996

Superoxide dismutase and catalase in protection of cardiopulmonary bypass-induced cardiac dysfunction and cellular injury.

BACKGROUND: Cardiac dysfunction following cardiopulmonary bypass (CPB) is well known. Various possible sources for increased levels of oxygen free radicals (OFRs) exist during CPB and OFRs depress cardiac function. Postpump (following CPB) cardiac dysfunction may be due to increased levels of OFRs. METHODS: This study investigated the effects of cold crystalloid cardioplegia with and without superoxide dismutase (SOD) and catalase (CAT) on cardiac function (cardiac index [CI], left ventricular work index [LVWI]), cardiac contractility (+dp/dt, +dp/dt/PAW [pulmonary arterial wedge pressure], +dp/dt/LVEDP [left ventricular end-diastolic pressure]), diastolic compliance (-dp/dt), OFR-producing activity of polymorphonuclear leukocytes (PMNL-CL); creatine kinase (CK) and MB isoenzyme of CK (MBCK), malondialdehyde (MDA), and white blood cells (WBC) and PMNLs from coronary sinus blood; and lactate levels in arterial blood in anesthetized dogs at various times (up to 90 mins) of reperfusion following 90 mins of hypothermic ischemic cardiac arrest. The dogs were divided into three groups: group I, sham bypass; group II, cold crystalloid cardioplegic cardiac arrest; group III, similar to group II but received SOD and catalase treatment. RESULTS: Postpump decreases in cardiac function, contractility and diastolic compliance were associated with increases in PMNL-CL activity, blood MDA, plasma CK and MBCK, and plasma lactate, and decreases in WBC and PMNLs. Prevention of postpump cardiac dysfunction (function and contractility) by SOD and CAT was associated with restoration in PMNL-CL activity, plasma CK and MBCK activity, and blood MDA towards control values although not complete. The levels of plasma lactate, total WBC and PMNLs were similar in group II and group III. CONCLUSIONS: These results suggest that postpump depression of cardiac function and contractility could be due to increased levels of OFRs and that SOD and CAT scavengers of superoxide anion and hydrogen peroxide respectively may be effective in preventing postpump cardiac dysfunction.

Animals↗
PubMed1995

Purification of a new clathrin assembly protein from bovine brain coated vesicles and its identification as myelin basic protein.

The multimeric clathrin assembly proteins AP-1 and AP-2 with molecular masses of approximately 270 kDa and the monomeric clathrin assembly proteins AP180 and auxilin with molecular masses of approximately 90 kDa catalyze the assembly of clathrin into artificial clathrin baskets under physiological conditions. We have now identified a much smaller approximately 20-kDa clathrin assembly protein in 0.5 M Tris, pH 7.0, extracts of bovine-brain coated vesicles and purified it to near homogeneity. A polyclonal antibody against this protein did not cross-react with any of the other assembly proteins, and sequencing data suggest that this new protein is similar or identical to myelin basic protein (MBP). At a molar ratio of 3 molecules per clathrin triskelion, MBP catalyzes polymerization of clathrin into artificial baskets that appear structurally similar to the baskets assembled by the other assembly proteins. In addition, like the other baskets, the clathrin-MBP baskets are uncoated by hsp70. MBP represents a significant fraction of the total assembly protein activity present in 0.5 M Tris, pH 7.0, extracts of coated vesicles. It is not clear if it acts as an assembly protein in vivo, but because it is well characterized and easily available, MBP will be a useful protein to investigate the mechanism of clathrin assembly and disassembly in vitro.

Adaptor Proteins, Vesicular Transport↗
PubMed1995

Role of auxilin in uncoating clathrin-coated vesicles.

Clathrin-coated vesicles transport selected integral membrane proteins from the cell surface and the trans-Golgi network to the endosomal system. Before fusing with their target the vesicles must be stripped of their coats. This process is effected by the chaperone protein hsp70c together with a 100K cofactor which we here identify as the coat protein auxilin. Auxilin binds with high affinity to assembled clathrin lattices and, in the presence of ATP, recruits hsp70c. Dissociation of the lattice does not depend as previously supposed on clathrin light chains or on the amino-terminal domain of the heavy chain. The presence of a J-domain at its carboxy terminus now defines auxilin as a member of the DnaJ protein family. In conjunction with hsp70, DnaJ proteins catalyse protein folding, protein transport across membranes and the selective disruption of protein-protein interactions. We show that deletion of the J-domain of auxilin results in the loss of cofactor activity.

Adaptor Proteins, Vesicular Transport↗
PubMed1995

Lipid peroxidation and activity of antioxidant enzymes in diabetic rats.

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.

Animals↗
PubMed1995

Antioxidant activity of allicin, an active principle in garlic.

Garlic has been claimed to be effective against diseases, in the pathophysiology of which oxygen free radicals (OFRs) have been implicated. Effectiveness of garlic could be due to its ability to scavenge OFRs. However, its antioxidant activity is not known. We investigated the ability of allicin (active ingredient of garlic) contained in the commercial preparation Garlicin to scavenge hydroxyl radicals (.OH) using high pressure liquid chromatographic (HPLC) method. .OH was generated by photolysis of H2O2 (1.25-10 mumoles/ml) with ultraviolet light and was trapped with salicylic acid which is hydroxylated to produce .OH adduct products 2,3- and 2,5-dihydroxybenzoic acid (DHBA). H2O2 produced a concentration-dependent .OH as estimated by .OH adduct products 2,3-DHBA and 2,5-DHBA. Allicin equivalent in Garlicin (1.8, 3.6, 7.2, 14.4, 21.6, 28.8 and 36 micrograms) produced concentration-dependent decreases in the formation of 2,3-DHBA and 2,5-DHBA. The inhibition of formation of 2,3-DHBA and 2,5-DHBA with 1.8 micrograms/ml was 32.36% and 43.2% respectively while with 36.0 micrograms/ml the inhibition was approximately 94.0% and 90.0% respectively. The decrease in .OH adduct products was due to scavenging of .OH and not by scavenging of formed .OH adduct products. Allicin prevented the lipid peroxidation of liver homogenate in a concentration-dependent manner. These results suggest that allicin scavenges .OH and Garlicin has antioxidant activity.

Animals↗
PubMed1995

Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary↗
PubMed1995

Is there increased sympathetic activity in patients with hypertrophic cardiomyopathy?

OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone.

Adolescent↗