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Biomedical subjects

J Mehta

Publications and source records attributed to J Mehta.

At least 271 records · Page 15Linked to original sources
PubMed1984

Thromboxane release in coronary artery disease: spontaneous versus pacing-induced angina.

To determine thromboxane A2 release in coronary artery disease, we measured its stable metabolite thromboxane B2 by radioimmunoassay in 20 patients. In 15 patients with stable disease (last angina episode greater than 96 hours before study), coronary venous thromboxane B2 concentrations were lower than in aortic blood (mean 109 +/- 36 vs 194 +/- 40 pg/ml, p less than 0.001). In contrast, in five other patients with spontaneous angina, coronary venous thromboxane B2 concentrations were higher than aortic thromboxane B2 concentrations during the angina episode (mean 1716 +/- 316 vs 875 +/- 388 pg/ml, p less than 0.02). Plasma thromboxane B2 levels were in the normal range (mean 175 +/- 35 pg/ml) in patients with stable angina but significantly (p less than 0.02) higher in patients with spontaneous angina. With atrial pacing to the point of chest pain and/or ECG changes in patients with stable coronary artery disease, aortic thromboxane B2 concentrations increased in 10 of 13 patients (mean 283 +/- 70 pg/ml, p less than 0.02). Coronary venous thromboxane B2 concentrations increased in seven patients at peak pacing rates (mean 223 +/- 76 pg/ml) and in three other patients after termination of pacing. These data indicate that release of thromboxane A2 is much greater during spontaneous angina than with pacing stress in patients with coronary artery disease. Thromboxane A2 released during spontaneous or pacing-induced angina may modulate coronary and systemic vascular tone. Enhanced thromboxane A2 activity may either precede or follow myocardial ischemia and could be a factor in the initiation and propagation of the ischemic episode.

Adult↗
PubMed1984

Effects of diltiazem, dipyridamole, and their combination on hemostasis.

Calcium channel blockers and antiplatelet agents, alone and in combination, have been reported to induce bleeding in patients undergoing surgery. Since diltiazem and dipyridamole influence platelet function in vitro and in vivo, their influence on hemostasis was examined in five normal men given diltiazem, 90 mg by mouth, followed by 60 mg every 6 hr for 48 hr, or dipyridamole, 75 mg by mouth every 8 hr for 48 hr. At 24 hr, the alternate drug was added to the regimen to assess effects of the combination on hemostasis. Platelet aggregation, serum thromboxane B2 and 6-keto-PGF1 alpha concentrations (stable metabolites of thromboxane A2 and prostacyclin), bleeding time, prothrombin time, partial thromboplastin time, and serum diltiazem concentrations were measured. Diltiazem and dipyridamole alone and in combination had no significant effect on bleeding time, prothrombin time, or partial thromboplastin time. Platelet aggregation induced by threshold concentrations of adenosine diphosphate, epinephrine, and calcium ionophore A 23187 were inhibited by diltiazem and dipyridamole alone and in combination. The only change in prostaglandin concentrations was a slight increase in serum 6-keto-PGF1 alpha after diltiazem. Despite influences on platelet function, neither diltiazem nor dipyridamole alone or in combination induced clinically relevant changes in hemostasis.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Prostacyclin release following endoperoxide analogue infusion in the intact dog.

We examined the systemic and coronary hemodynamic responses after infusion of an endoperoxide analogue U 46,619 in anesthetized dogs and related the hemodynamic effects to the release of thromboxane A2 (TXA2) and prostacyclin (PGI2). Immediately after U 46,619 infusion, increases in mean arterial and left ventricular end-diastolic pressures (LVEDP) occurred, whereas coronary and aortic blood flows were unchanged. Calculated vascular resistances in the systemic and coronary vascular beds increased significantly. At 3-5 min after infusion, mean arterial pressure and LVEDP spontaneously decreased and vascular resistances also declined, whereas coronary and aortic blood flows were unchanged. Simultaneously measured plasma TXB2 and 6-keto-PGF1 alpha (stable hydrolysis metabolites of TXA2 and PGI2, respectively) increased in the femoral and coronary arterial blood samples in conjunction with the vasoconstrictor effects. At 3-5 min, plasma 6-keto-PGF1 alpha concentrations showed a further increase, whereas TXB2 concentrations slightly decreased, suggesting release of PGI2 as a possible mechanism of vasodilation. To examine this possibility, nine dogs were treated with cyclooxygenase inhibitors (aspirin or indomethacin) and given U 46,619. In these animals neither vasoconstrictor nor vasodilator effects were observed. Plasma TXB2 and 6-keto-PGF1 alpha concentrations also did not increase after U 46,619. These data show that the vasoconstrictor and platelet aggregatory agent U 46,619 results in PGI2 release in the dog. Release of PGI2 may be a protective and autoregulatory mechanism in the canine systemic and coronary vascular beds.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1984

Binding characteristics of radioiodinated crystal-induced chemotactic factor to human neutrophils.

The binding of radiolabeled crystal-induced chemotactic factor (CCF) to human neutrophils is characterized. Binding of 125I-CCF to the cells was higher at 4 degrees C than at 24 degrees or 37 degrees C and was found to be independent of CA2+ and Mg2+ ion concentration. The binding showed a pH optimum of 6.0. Tosylamido phenylethyl chloromethyl ketone at 100 mumol/L concentration inhibited 20% of 125I-CCF binding, but phenylmethylsulfonyl fluoride at 200 mumol/L had no effect. Approximately 50% of cell-associated 125I-CCF was released after treatment with proteases. The nonspecific uptake by the cells, as measured by the uptake of 3H-sucrose and 14C-inulin in the presence of CCF, was negligible. After the steady-state binding of 125I-CCF to the cells, approximately 15% of the cell-associated radioactivity at 4 degrees C and 40% to 50% at 24 degrees and 37 degrees C was released into the medium after 60 minutes of incubation in medium alone. Dissociation of the radioactive material was not affected by the presence of tosylamido phenylethyl chloromethyl ketone or phenanthroline in the media. The dissociated material was determined to be degraded 125I-CCF, suggesting that degradation of 125I-CCF occurs after binding to its specific receptor on the human neutrophil.

Calcium↗
PubMed1984

Lipid composition of the peripheral nerves in malnutrition: an experimental study in young rhesus monkeys.

An experimental model of protein calorie malnutrition (PCM) was created in young rhesus monkeys. Ulnar and tibial nerves from six monkeys with PCM, six rehabilitated and 12 control monkeys were studied for lipid composition and activity of myelin marker enzyme. Total lipids, myelin marker lipids and activity of myelin marker enzyme, 2', 3'-cyclic nucleotide 3' - phosphohydrolase were decreased, while esterified cholesterol and free fatty acids were increased in PCM as compared to controls. There was partial recovery in myelin marker lipids and complete restoration of other lipids on nutritional rehabilitation.

Animals↗
PubMed1984

In vitro incorporation of (U-C14)-glucose and (1-C14)-sodium acetate in peripheral nerves of malnourished young rhesus monkeys.

The effect of protein calorie malnutrition (PCM) on synthesis of lipids in peripheral nerves was studied by in vitro incorporation of (U-C14)-glucose and (1-C14)-sodium acetate. Ulnar and tibial nerves obtained from five young rhesus monkeys with PCM, five rehabilitated monkeys, and five control monkeys were incubated for 2 h with the radioactive precursors. Uptake of both radioactive precursors in whole peripheral nerves as well as myelin marker lipids was significantly decreased in animals with PCM. However, uptake returned to normal in rehabilitated monkeys.

Acetates↗
PubMed1983

Systemic, pulmonary, and coronary hemodynamic effects of labetalol in hypertensive subjects.

Long-term therapy with oral labetalol, an alpha- and beta-blocking agent, has been shown to effectively lower blood pressure and heart rate without decreasing cardiac output. We examined the hemodynamic effects of the acute intravenous administration of labetalol in nine hypertensive patients. Labetalol (0.6 +/- 0.1 mg/kg) promptly reduced arterial pressure, heart rate, and systemic vascular resistance without change in stroke volume. Heart rate responses to passive tilt and the Valsalva maneuver were significantly blunted. With isometric exercise, heart rate and mean arterial pressure increased significantly during labetalol therapy but less than in the pre-labetalol phase. In eight patients oral labetalol therapy was continued for six weeks (mean dose 1,050 +/- 105 mg/day), and hemodynamic evaluation was repeated. During oral labetalol therapy, decreases in arterial pressure and heart rate were sustained. Systemic vascular resistance was reduced in five of the eight patients. Hemodynamic responses to tilt, Valsalva maneuver, and handgrip were similar to those during intravenous administration. Coronary blood flow decreased, but coronary as well as pulmonary vascular resistances were unchanged. These data show the efficacy of intravenously administered labetalol in lowering blood pressure and systemic vascular resistance promptly. With long-term oral therapy, decreases in blood pressure are sustained. Labetalol does not appear to have significant effects on pulmonary or coronary vascular resistances.

Adult↗
PubMed1983

Effects of verapamil on platelet aggregation, ATP release and thromboxane generation.

We examined the effects of verapamil on platelet function. Verapamil (0.5 micrograms/ml) in this study inhibited platelet aggregation induced by threshold amounts of ADP, AA, and epinephrine. With higher concentrations of aggregating stimuli, verapamil caused a dose-dependent inhibition of aggregation. Verapamil reduced the extent of epinephrine-induced primary wave, but not that by ADP. Ristocetin-induced aggregation was not affected at any concentration of verapamil. Platelet ATP release induced by AA and ADP was also inhibited. In vitro platelet TXA2 generation was inhibited by verapamil in concentrations lower than those required for inhibition of aggregation.

Adenosine Triphosphate↗
PubMed1983

Heterologous receptor population for a chemotactic factor F-Met-Leu-Phe on the human neutrophil. Effect of pH and temperature.

Association kinetics of a chemotactic factor [3H]FMLP to its specific receptors on human neutrophils and the modulation of kinetic constants by pH and temperature were studied. The half-time for [3H]FMLP association to its specific receptors as calculated by a least-square fit equation was 27 min at 4 degrees C, 13 min at 24 degrees C, and 5 min at 37 degrees C. The Scatchard plot of [3H]FMLP binding to its specific receptors was found to be nonlinear, suggesting a heterogeneity of [3H]FMLP receptors and/or functional negative cooperativity. The computer analysis of the data showed two populations of FMLP receptors on human neutrophils with Kd (dissociation constant) values of 0.17 +/- SD 0.1 nM and 0.94 +/- SD 0.1 nM at 4 degrees C, and 0.17 +/- SD 0.02 nM and 1.1 +/- SD 0.2 nM at 37 degrees C. The optimum [3H]FMLP binding at 37 degrees C was observed at pH 7.5. There was essentially no difference in Kd values at pH 6.0, 7.5, or 8.5. Our results suggest the presence of two populations of [3H]FMLP receptors on human neutrophils in support of previous observations of other investigators. Our data also demonstrate that association constants between [3H]FMLP and its specific receptors on human neutrophils are not affected by changes in pH or temperature; maximal binding, however, is dependent on pH.

Humans↗
PubMed1983

Clinical outcome after treatment of rest angina with calcium blockers: comparative experience during the initial year of therapy with diltiazem, nifedipine, and verapamil.

The clinical outcome after the initial year of therapy with either diltiazem (D), nifedipine (N), or verapamil (V) was examined in 45 patients with rest angina. Age, frequency of angina, duration of symptoms, and ejection fraction were similar in all three treatment groups. Coronary artery disease was present in 60% of patients (5 of 13 given D, 8 of 16 given N, and 14 of 16 given V). Coronary spasm was suspected (ST elevation with angina) or documented (angiographically) in 35 (78%) patients. Twenty-nine (64%) patients had greater than 50% decrease in angina without a coronary event (9 taking D, 11 taking N, and 9 taking V). Coronary events (sudden death, infarction, and hospitalization for unacceptable angina control or bypass surgery) occurred in 13 (29%) patients (two taking D, four taking N, and seven taking V). To achieve these responses, 20 (44%) patients required additional antianginal drugs (long-acting nitrates, beta blockers, or other calcium blockers). Four of these 20 patients were taking D, nine were taking N, and seven were taking V. Seventeen (38%) patients experienced a side effect (none taking D, 6 taking N, and 11 taking V). Although rest angina can be controlled in the majority of patients during the initial year of treatment with calcium blockers, additional therapy is often required. Furthermore, the clinical course of patients presenting with rest angina remains unpredictable, even during calcium blocker treatment. Morbid events continue to occur, related in part to the extent of coronary artery disease.

Adult↗
PubMed1983

The significance of platelet-vessel wall prostaglandin equilibrium during exercise-induced stress.

Alterations in platelet-generated thromboxane A2 (TXA2) and vessel wall-generated prostacyclin (PGI2) have been associated with myocardial ischemia. To examine TXA2-PGI2 equilibrium at rest and during exercise stress, we studied 13 normal subjects and 15 coronary artery disease patients. Plasma TXB2 and 6-keto-PGF1 alpha were measured as stable metabolites of TXA2 and PGI2, respectively, by radioimmunoassay. In normal subjects, plasma TXB2 levels increased 24% during exercise from 135 +/- 30 to 168 +/- 42 pg/ml (p = NS). Plasma 6-keto-PGF1 alpha levels increased 224% from 54 +/- 17 to 175 +/- 57 pg/ml (p less than 0.05). In coronary artery disease patients, although resting plasma TXB2 levels (mean 136 +/- 43 pg/ml) were comparable to levels in normal subjects, a greater increase (82%) occurred during exercise (mean 248 +/- 70 pg/ml; p less than 0.02 compared to resting levels). Resting plasma 6-keto-PGF1 alpha levels (mean 94 +/- 28 pg/ml) were also similar to normal subjects but increased only by 43% during exercise (mean 134 +/- 53 pg/ml; p = NS compared to resting levels). These data suggest that: in normal subjects TXA2 and PGI2 increase during exercise, PGI2 increasing more than TXA2, and although coronary disease patients have resting TXA2 and PGI2 levels in the normal range, TXA2 levels increase more than PGI2 levels during exercise. These observations may have a bearing on the mechanism of exercise-induced angina pectoris in certain coronary artery disease patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Effect of different amounts of arachidonic acid on vessel wall-generated PGI2 and TXA2.

It has been suggested that low concentrations of AA may have vasoprotective and high concentrations vaso-damaging effects. To relate these effects to vascular generation of PGI2 and TXA2, we incubated human umbilical vein rings with AA (0, 0.01, 0.1, 1 and 2 mM) and examined the supernates for 6-keto-PGF1 alpha and TXB2. Low concentrations of AA (0.01 and 0.1 mM) caused preferential and maximal PGI2 release, whereas higher concentrations (1 and 2 mM) resulted in marked and preferential increase in TXA2 release. Disequilibrium in vascular PGI2 and TXA2 release towards the latter may relate to vaso-damaging effects of high concentrations of AA.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Stimulation of vessel wall prostacyclin by selective thromboxane synthetase inhibitor OKY 1581.

Human umbilical veins have been shown to produce small amounts of TXA2 in addition to PGI2. We measured relative TXA2 and PGI2 production by umbilical veins in the presence of selective TXA2 synthetase inhibitor OKY 1581. OKY 1581 treatment resulted in inhibition of TXA2 but a marked increase in PGI2 release, which may relate to diversion of cyclic endoperoxides to PGI2 pathway or to removal of a feedback control at the level of AA mobilization.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Increased plasma concentrations of prostacyclin metabolite 6-keto-PGF1 alpha in essential hypertension. Influence of therapy with labetalol.

To evaluate the role of the vasoactive prostaglandins prostacyclin and thromboxane A2 in essential hypertension, the stable metabolites 6-keto-PGF1 alpha and thromboxane B2, respectively, were measured in plasma before and after therapy in 7 patients. During the placebo phase, plasma 6-keto-PGF1 alpha levels were significantly greater than normal. Plasma thromboxane B2 levels were not statistically different from those in normal subjects. After intravenous administration of labetalol to the point of blood pressure reduction, neither plasma 6-keto-PGF1 alpha nor thromboxane B2 values changed. With prolonged oral labetalol therapy and concurrent regulation of blood pressure, a significant decrease in plasma 6-keto-PGF1 alpha levels occurred while thromboxane B2 values remained unaltered. Elevation of plasma 6-keto-PGF1 alpha in untreated hypertensive subjects suggests that enhanced vessel wall prostacyclin synthesis may be a protective mechanism to prevent organ damage. As blood pressure is controlled this increase is no longer needed, and prostacyclin generation returns to normal.

Administration, Oral↗