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Biomedical subjects

K Prasad

Publications and source records attributed to K Prasad.

At least 181 records · Page 10Linked to original sources
PubMed1991

Influence of endothelin on cardiovascular function, oxygen free radicals, and blood chemistry.

Endothelin, a peptide that is derived from vascular endothelial cells, is a potent constrictor of mammalian blood vessels in in vitro studies. Various clinical conditions have been reported to be associated with an increase in the blood and tissue levels of endothelin. In the present study, the effects of two doses (2.059 and 4.118 micrograms/kg, intravenously) of endothelin on cardiac function and contractility; blood lactate, gases, and pH levels; blood and cardiac tissue MDA levels; PMN leukocyte chemiluminescence activity; and total WBC and PMN leukocyte counts were investigated in anesthetized dogs. Hemodynamic measurements and collection of blood samples for various biochemical measurements were made before and at various intervals up to 2 hours after endothelin administration. Endothelin in the large dose (4.118 micrograms/kg) produced a prolonged decrease in the indices of cardiac contractility and cardiac function and increases in TSVR, PVR, and mean right atrial pressure. The changes in the hemodynamic parameters with the smaller dose (2.059 micrograms/kg) were similar but of smaller magnitude. Significant decreases in dp/dt at CPIP:PAW and CI and increases in TSVR and PVR were observed with the smaller dose of endothelin. There were decreases in the blood HCO3- and pH levels and an increase in H+ and blood lactate concentration and CK activity with the high dose of endothelin. No changes were observed in blood PO2 and PCO2 with either dose of endothelin. Circulating WBCs and PMN leukocytes decreased significantly with both doses of endothelin. There were no changes in the oxygen free radical-producing activity of PMN leukocytes and in the blood and cardiac tissue MDA levels. These results suggest that endothelin decreased cardiac function and cardiac contractility and increased SVR and PVR. The decrease in cardiac function and contractility may be due to ischemia from constriction of coronary arteries. The hemodynamic changes are unlikely be due to oxygen free radicals since there was no increase in the blood and cardiac tissue MDA levels and no change in the PMN chemiluminescence. These studies suggest that increases in endothelin levels in certain clinical conditions might cause added deleterious effects on cardiovascular function.

Animals↗
PubMed1991

POEMS syndrome.

A patient with peripheral polyneuropathy, hepatosplenomegaly, osteosclerotic myeloma in the ilium, hyperpigmentation and hypertrichosis is described. A diagnosis of POEMS syndrome was made. This is the first report of this syndrome from India.

Adult↗
PubMed1991

Increased production of oxygen free radicals in cigarette smokers.

Oxygen free radicals are known to produce damage in many biological tissues. Cigarette smoking is a major risk factor for various diseases. It is possible that oxygen free radical producing activity of polymorphonuclear (PMN) leucocytes is increased by cigarette smoking. We studied the oxygen free radical producing (luminol-dependent chemiluminescent) activity of PMN leucocytes in blood and the malondialdehyde (lipid peroxidation product) content of blood and serum in nonsmokers and smokers. The zymosan-induced chemiluminescent activity was measured on a LKB 1251 luminometer. The malondialdehyde (MDA) was measured as thiobarbituric acid (TBA) reactive substances. The chemiluminescent activity due to oxygen-derived free radicals (superoxide anion, hydrogen peroxide, hydroxyl radical) and superoxide dismutase (SOD)-inhibitable (superoxide anion) in nonsmokers were 1215.1 +/- 91.1 and 849.3 +/- 72.3 mV min/10(6) PMN leucocytes respectively. There was a significant increase in the oxygen-derived free radicals and SOD-inhibitable chemiluminescence in smokers. The values of blood and serum MDA were 171.7 +/- 6.1 and 222.2 +/- 5.6 nmoles/l respectively in nonsmokers. There was an increase in both blood and serum MDA in smokers. These results suggest that the increased generation of oxygen free radicals by PMN leucocytes might be responsible for an enhanced risk of various diseases related to cigarette smoking.

Adult↗
PubMed1990

Effect of oxygen free radicals, hypoxia and pH on the release of liver lysosomal enzymes.

We investigated the effect of acidic environment, hypoxia and oxygen free radicals on the release of beta-glucuronidase from rat liver lysosomes. A lysosomal enriched fraction from the homogenate of rat liver was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of beta-glucuronidase activity was measured from the lysosomes. The lysosomal fraction was exposed to various pH (8.0, 7.4, 6.5, 6.0, 5.5) and pO2 (454, 172, 96, 57,34 mm Hg) separately or to a combination of low pH (5.5, 6.5) and low pO2 (34, 57 mm Hg). The changes in pH or pO2 separately did not cause any increase in the release of beta-glucuronidase activity. The presence of oxygen free radicals at each pH or pO2 resulted in about a 3-fold increase in the release of beta-glucuronidase. A combination of very low pO2 and pH (pO2 (mm Hg)/pH; 34/5.5, 34/6.5) resulted in an increased release of beta-glucuronidase from lysosomes. Oxygen free radicals in the presence of both low pO2 and pH resulted in a further increase in the release of beta-glucuronidase. These data indicate that oxygen free radicals and not the alterations in pH and/or pO2 are primarily responsible for the disruption of lysosomes.

Animals↗
PubMed1990

Surgical treatment of major intracardiac lesions associated with discordant atrioventricular connexion.

Thirteen patients with a discordant atrioventricular connexion underwent repair of major associated intracardiac defects. Of the patients, 10 had a discordant ventriculoarterial connexion while 3 had double outlet from the morphologically right ventricle. A ventricular septal defect was the most frequently encountered lesion, present alone or in combination with other lesions in all patients. The other major lesions were pulmonary stenosis in 8, Ebstein's malformation of the left atrioventricular valve in 2, and calcific aortic valve disease in one. The operations performed were closure of the ventricular septal defect in 4 patients, closure of the ventricular septal defect with pulmonary valvotomy in 3 patients (one of whom subsequently underwent replacement of the left atrioventricular valve). Modified Fontan's procedure was performed in 6 patients, one of whom also had replacement of the aortic valve. There was no operative death, although there was one early death on the 40th postoperative day due to septicemia. There has been no late death after an average follow-up of 1.2 years. There was one case of surgically induced complete heart block. All other patients are in normal sinus rhythm in New York Heart Association functional class I or II. Elective repair of major intracardiac anomalies in association with a discordant atrioventricular connexion can now be accomplished safely. The modified Fontan's procedure is a viable alternative in certain cases to the placement of an external valved conduit for relief of pulmonary outflow tract obstruction.

Adolescent↗
PubMed1990

Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters.

Polymorphonuclear (PMN) leukocyte activation is known to result in the production and release of oxygen free radicals and hypochlorous acid. Various clinical conditions are associated with PMN leukocyte stimulation. The present investigation deals with the effects of stimulated PMN leukocytes in the absence and in the presence of scavengers of oxygen free radicals (superoxide dismutase, catalase), hypochlorous acid quencher (methionine), and myeloperoxidase inhibitor (azide) on cardiac function and contractility; blood lactate, gases, and pH levels, blood and cardiac tissue malondialdehyde; and PMN leukocyte chemiluminescence activity in anesthetized dogs. Opsonised zymosan was used for stimulation of PMN leukocytes, and the effects were observed for 2 hours. The dogs were divided into four groups: group I, zymosan; group II, superoxide dismutase + catalase + zymosan; group III, methionine + zymosan; group IV, azide + methionine + zymosan. Zymosan produced a decrease in cardiac function and in indices of myocardial contractility and an increase in systemic and pulmonary vascular resistance. There was a decrease in blood pH and in PMN leukocyte chemiluminescense and an increase in the blood lactate and malondialdehyde. Superoxide dismutase plus catalase and methionine reduced the effect of zymosan on cardiac function and contractility and on blood malondialdehyde, lactate, and pH. The combination of azide and methionine did not prevent the deleterious effects of zymosan on cardiac function and contractility. Cardiac tissue malondialdehyde levels were lower in groups III and IV than in groups I and II which had values similar to each other. Methionine was superior to superoxide dismutase plus catalase in the prevention of the deleterious effects of PMN leukocyte stimulation on the various measured parameters. These results suggest that oxygen free radicals and hypochlorous acid are cardiac depressants and increase systemic and pulmonary vascular resistance in addition to causing tissue damage. Clinical situations with PMN stimulation may result in cardiac depression. The oxygen free radical scavenger and hypochlorous acid quencher may be beneficial in the counteraction of the deleterious effects of PMN leukocyte stimulation on the hemodynamic parameters and cellular integrity.

Animals↗
PubMed1990

Effects of diltiazem on the functional recovery of the myocardium at organ and cellular level during prolonged hypothermic ischemic cardiac arrest.

The effectiveness of diltiazem on the functional recovery of the heart, calcium (Ca++) uptake and binding, Ca++ ATPase of cardiac sarcoplasmic reticulum (SR), and MB fraction of creatine kinase (MBCK) of coronary sinus blood was investigated after one and a half hours of reperfusion following three hours of ischemic cardiac arrest. The dogs were divided into three groups: group I, sham bypass; group II, cold crystalloid cardioplegia; and group III, cold crystalloid cardioplegia with diltiazem. There was a decrease in aortic pressures left ventricular pressure development (dp/dt), left ventricular work index (LVWI), total systemic vascular resistance (TSVR), and left ventricular systolic pressure (LVSP) in the sham bypass group. There was a decrease in cardiac index (CI), LVWI, and mean right atrial pressure (mRAP) and an increase in TSVR and pulmonary vascular resistance (PVR) in group II as compared with group I. Although there was a tendency for a decrease in the indices of myocardial contractility in group II, they were not significantly different from those in group I. The indices of myocardial contractility, CI, and LVWI in group III were slightly higher than in group II, but they were not significantly different from each other. The values for calcium uptake by SR in groups II and III were similar but significantly lower than those in group I. Calcium binding in group III was significantly lower than that in group I. Calcium ATPase of SR in the three groups were similar. Although MBCK increased in all the groups, the increases were not significantly different among the three groups. The results of this study indicate that cold crystalloid cardioplegia with diltiazem was not better than cold crystalloid alone in preserving the cardiac contractility and cellular function during prolonged ischemic cardiac arrest. However, the cardiac function in terms of cardiac index was better preserved with diltiazem.

Adenosine Triphosphatases↗
PubMed1989

Organization of clathrin coat structures.

Clathrin (8S), when purified, polymerizes under low-pH conditions (0.1 M MES, pH 6.0-6.2) into a heterogeneous population of baskets with sedimentation coefficients ranging from 150 to 400 S. Several groups of proteins of molecular masses 180, 110, 100, 50, and 47 kDa (based on sodium dodecyl sulfate gel electrophoresis) present in the isolated coated vesicles are involved in polymerizing clathrin under physiological conditions to a homogeneous population of baskets [Zaremba, S., & Keen, J. H. (1983) J. Cell Biol. 97, 1339; Ahle, S., & Ungewickell, E. (1986) EMBO J. 5, 3143]. We now report that in 0.1 M MES, pH 6.0, where pure clathrin polymerizes by itself, the above proteins (together known as associated proteins or APs) induce polymerization of clathrin into three distinct sizes of baskets with sedimentation coefficients of 150, 220, and 300 S. Low ratios of clathrin to APs give rise to smaller sizes, whereas higher ratios give rise to predominantly the larger sizes. The smaller size baskets (150S) are intermediates in the polymerization of clathrin to larger size baskets (300S) as inferred from the dissociation of larger size baskets into smaller size baskets and the formation of larger size baskets from smaller size baskets upon the addition of pure clathrin.

Adaptor Proteins, Vesicular Transport↗
PubMed1989

Effect of oxygen free radicals on cardiovascular function at organ and cellular levels.

Oxygen free radicals (OFR) have been implicated as a causative factor of cell damage in several pathologic conditions. It is possible that OFR could have effects on cardiac function and contractility. The present investigation deals with the effects of OFR in the absence and in the presence of scavangers of OFR (superoxide dismutase and catalase) on cardiac function, index of cardiac contractility, serum creatine kinase (CK), and blood lactate, PO2 and pH in the anesthetized dogs. The hemodynamic measurements and collection of blood samples for measurement of CK, lactate, PO2 and pH were made before and at various intervals after administration of OFR for 1 hour. Xanthine and xanthine oxidase were used to generate OFR. OFR produced a decrease in cardiac function and indices of myocardial contractility and an increase in the serum CK. OFR produced an increase in the systemic and pulmonary vascular resistance. Although there was a tendency for an increase in the blood lactate, the increase was not significant. The blood PO2 and pH were not affected. Superoxide dismutase (SOD), alone or in combination with catalase, tended to protect cardiac function against the deleterious effects of OFR. Scavangers of OFR prevented the OFR-induced rise in serum CK. Although the protective effect of SOD plus catalase was slightly better than SOD alone, the results were not significantly different from each other. These results suggest that OFR are cardiac depressant and increase the peripheral vascular resistance besides causing cellular damage. Scavangers of OFR may be beneficial in counteracting the deleterious effects of OFR on hemodynamic parameters and cellular integrity.

Animals↗
PubMed1989

Role of oxygen free radicals and pH on the release of cardiac lysosomal enzymes.

We investigated the effect of exogenous oxygen free radicals and various pH on the release of lysosomal hydrolases from dog myocardial lysosomes. A lysosomal enriched fraction from the homogenate of dog heart was prepared, using differential centrifugation technique. Exogenous oxygen free radicals were generated using xanthine-xanthine oxidase system. The release of lysosomal hydrolases was measured from the lysosomal enriched fraction. There was about 3-fold increase in the release of cathepsin D and beta-N-acetylglucosaminidase activities in the preparations treated with xanthine-xanthine oxidase as compared to those without such treatment. The presence of superoxide dismutase, an oxygen free radical scavenger, prevented the release of cathepsin D and beta-N-acetylglucosaminidase from the lysosomes. Sonication and lubrol treatments, which are known to cause membrane disruption, also induced the release of these enzymes from lysosomal enriched fraction. However, this release was not prevented by superoxide dismutase. The changes in pH (4.5, 5.5, 6.0, 6.5, 7.4, 8.0) alone did not cause any increase in the enzyme release. The presence of oxygen free radicals at each pH resulted in a similar increase in the release of cathepsin D and beta-N-acetylglucosaminidase. These studies suggest that oxygen free radicals and not the alterations in pH are primarily responsible for the release of lysosomal hydrolases. Oxygen free radicals, in addition to their direct myocardial damaging effect, may also be responsible for the cardiac damage through the release of lysosomal enzymes.

Acetylglucosaminidase↗
PubMed1989

Increased production of oxygen free radicals by polymorphonuclear leukocytes in heart failure due to aortic stenosis.

Oxygen free radicals have been linked to a wide variety of cellular damage in biological systems. Polymorphonuclear (PMN) leukocytes stimulation is one of the known sources for oxygen free radicals. It has been suggested that oxygen free radicals depress the excitation-contraction coupling in cardiac muscle. It is possible that a decrease in the myocardial contractility in heart failure might be due to an increased oxygen-free-radical-producing activity of PMN leukocytes. The authors studied, therefore, the release of oxygen free radicals, as measured by luminol-dependent chemiluminescence activity, from the PMN leukocytes in dogs with heart failure due to aortic stenosis. Hemodynamics and phagocytic activity of PMN leukocytes were studied in 6 control dogs and 6 dogs with aortic stenosis of six to nine months' duration. There was a significant decrease in the index of myocardial contractility and an increase in the left ventricular end-diastolic pressure in dogs with aortic stenosis, suggesting left ventricular failure in these dogs. Although there was a tendency for a decrease in the cardiac index in dogs with aortic stenosis, the decrease was not significant. Phagocytic activity of PMN leukocytes in blood was studied in control dogs and dogs with aortic stenosis. Phagocytosis was initiated by addition of opsonized zymosan and chemiluminescence was monitored by use of a luminometer. The peak chemiluminescence activity of the PMN leukocytes in blood of dogs with heart failure was about threefold greater than that in the blood from control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Experimental atherosclerosis and oxygen free radicals.

Oxygen free radicals are known to produce cellular injury by peroxidation of phospholipids in the cell membrane. These free radicals might damage the endothelial cell and thus set the stage for atherosclerosis. The authors studied the effect of high-cholesterol diets on the genesis of atherosclerosis and lipid peroxidation products, malondialdehyde (MDA) in rabbits. The animals were divided into four groups each comprising 5 rabbits, on the basis of their diets. Group I, control diet; group II, cholesterol; group III, coconut oil; group IV, a mixture of cholesterol, coconut oil, and cholic acid. Rabbits were sacrificed five months after being on the respective diets. Blood samples were obtained for the measurements of total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglycerides, and MDA at the end of the protocol. The aortas were removed from different animals for the identification of atherosclerotic plaques. Plaques were detected in all the animals in group II and group IV. The serum total cholesterol, LDL-C, and VLDL-C were significantly higher in animals of group II and IV than in those of group I. The values for serum total cholesterol, HDL-C, LDL-C, and VLDL-C in group III were not significantly different from those in group I. The blood MDA and serum triglycerides were also higher in animals of group II and IV than in those of group I. There were, however, no significant differences in these parameters in group III as compared with those in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗