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Biomedical subjects

J Mehta

Publications and source records attributed to J Mehta.

At least 343 records · Page 19Linked to original sources

Precipitation of heart failure following sudden withdrawal of hydralazine.

Sudden withdrawal of oral therapy with hydralazine for reduction of afterload in a patient precipitated severe congestive heart failure. Signs of metabolic encephalopathy evolved due to low cardiac output. Reinstitution of therapy with hydralazine resulted in prompt improvement in cardiac and neurologic status. This case underscores the need for careful follow-up of such patients and argues against sudden withdrawal of vasodilator therapy.

Administration, Oral↗

Chemotactic factor-induced superoxide radical generation by human neutrophils: requirement for proteinase (esterase) activity.

The requirement for proteinase (esterase) activity in the generation of O2- by human peripheral neutrophils was investigated. Neutrophils were activated by exposure to the chemotactic peptide FMLP and superoxide generation was assessed by ferricytochrome C reduction. Inhibition of O2- generation was observed by pretreating cells with the chloromethyl ketone derivatives of tosyl-phenylalanine (TPCK, ID50 2.2 X 10(-5)M) and tosyl-lysine (TLCK, ID50 1.9 X 10(-4)M). Dose-dependent inhibition was also noted with synthetic proteinase substrates, especially those of chymotrypsin-like specificity, phenylalanine and tryptophan methyl esters (ID50S approximately 1.5 X 10(-4)M), as compared to derivatives of basic amino acids, arginine and acetyl-lysine methyl esters, which caused negligible inhibition at 10(-3M. The inhibition of O2- generation demonstrated by TryME was time- and temperature-dependent and reversible with washing of the cells, whereas the inhibition seen with TPCK was irreversible. DFP at high concentrations, 10(-3)M or greater, caused moderate inhibition of O2- generation that was unaffected by exogenous serine and almost completely reversible by washing the cells. TPCK and TryME, at concentrations that caused marked inhibition of O2- generation, had no effect on the fmlp-induced calcium-45 uptake by the cells. These studies suggest that intact proteinase function is required for O2- generation and that this step follows the calcium influx in the activation sequence induced by FMLP.

Calcium↗

Effect of altered lymphocyte function on immunologic disorders in NZB/NZW mice. III. Acceleration of disease by thymosin.

Administration of thymosin fraction V to NZB/NZW F1 mice, an animal model for human SLE, accelerated the appearance of proteinuria and anti-nDNA antibodies, increased deposition of immunoglobulins in kidneys, and significantly shortened survivals. Although the addition of thymosin to in vitro cultures of spleen and lymph node cells from thymosin-treated mice increased DNA synthesis in response to stimulation with Con A, in vivo treatment with thymosin did not affect the Con A response. There was no effect on in vitro responses to PHA or LPS, or on IgM antibody formation to SRBC (T cell dependent) or SSS III (T cell independent) immunizations. Antibodies to thymosin or contamination of our thymosin preparations with nucleic acids could not be demonstrated. The acceleration of autoimmune disease produced by thymosin treatment could not be explained by alteration of the T and B cell functions studied.

Animals↗

Non-parenteral combined afterload and preload reduction therapy in congestive heart failure.

It has been shown that hydralazine is beneficial in chronic heart failure by virtue of its afterload reducing effect. Nitroglycerin paste results in venodilation and fall in left ventricular filling pressure (LVFP). Thirteen patients with chronic heart failure were given a combination of oral hydralazine and nitroglycerin paste. With oral hydralazine (75 to 100 mg every 8 h), left ventricular stroke work increased and LVFP slightly fell. Following addition of 2% nitroglycerin paste, an additional decline in mean pulmonary artery and LVFP was observed without significant changes in heart rate and arterial pressure. There were no untoward side effects from either therapy. Eight patients followed for three to eight months (mean five months) reported subjective improvement in shortness of breath and other symptoms related to ventricular dysfunction. This study shows that in certain patients with chronic heart failure, hydralazine and nitroglycerin paste combination produces salutary clinical effects on long term probably through afterload and preload reduction, respectively.

Adult↗

Differences in platelet aggregation in coronary sinus and aortic blood in patients with coronary artery disease: effect of propranolol.

Platelet aggregation was studied in aortic and coronary sinus blood samples obtained from 18 patients with coronary artery disease (CAD). Using epinephrine and ADP as aggregating agents, platelet aggregation was lower in coronary venous blood than in aortic blood. In nine patients on long-term propranolol therapy, platelet aggregation was lower in both aortic and coronary venous blood compared to the nine patients not taking propranolol. Four other subjects without angiographic evidence of coronary disease exhibited no difference in platelet aggregation in aortic and coronary sinus blood. These data suggest that platelet aggregation is lower in the coronary venous blood of certain patients with coronary disease and chronic propranolol treatment may reduce aggregation in both aortic and coronary sinus blood.

Adult↗

Platelet aggregation studies in coronary artery disease. Past 4. Effect of aspirin.

We evaluated platelet aggregation in vitro in blood samples drawn simultaneously from aorta and coronary sinus. Platelet aggregation was significantly lower in the coronary venous blood than in the aortic blood in patients with coronary artery disease. Lower platelet counts were also observed in coronary venous blood. No such differences were seen in subjects with normal coronary arteries. Oral administration of aspirin eliminated the differences in platelet aggregation and counts across the myocardial vascular bed. These observations suggest that platelet sequestration in the myocardial vasculature may be related to the presence of disease in the coronary arteries.

Adult↗

Haemodynamic effects of hydrallazine and of hydrallazine plus glyceryl trinitrate paste in heart failure.

In a study designed to investigate potential non-parenteral treatment for chronic heart failure, hydrallazine, 225 to 300 mg per day, was given orally to 9 patients. There was no significant change in heart rate or mean arterial pressure as cardiac output increased. Left ventricular stroke work increased significantly and pulmonary artery wedge pressure fell. Systemic and pulmonary vascular resistances fell. With the addition of 2 per cent glyceryl trinitrate paste, there was a further decline in mean pulmonary arterial and wedge pressures, without a significant change in heart rate, arterial pressures, cardiac output, or systemic or pulmonary vascular resistance. There were no untoward effects from either form of treatment. All patients reported relief of shortness of breath and other symptoms related to ventricular dysfunction. This study supports the suggestion that oral hydrallazine is effective in increasing cardiac output and decreasing pulmonary congestion. Furthermore, the addition of topical glyceryl trinitrate provides a greater reduction of pulmonary pressures, probably through its predominant venodilator action. In some selected patients with heart failure, oral hydrallazine and topical glyceryl trinitrate in combination produce beneficial clinical and haemodynamic effects, probably through afterload and preload reduction, respectively.

Adult↗

In vivo validation of a thermodilution method to determine regional left ventricular blood flow in patients with coronary disease.

Several methods have been used to measure left ventricular regional blood flow in humans. However, limitations and lack of validation in patients are major problems. A continuous thermodilution technique to measure regional left ventricular blood flow in patients with coronary disease was validated in vivo. This technique permits simultaneous assessment of venous blood flow draining predominantly from the anterior wall and of the total left ventricular effluent. Thermodilution measurements with simultaneous electromagnetic flowmeter recordings from anterior descending vein grafts were compared in patients with occluded or subtotally occluded anterior descending coronary arteries. The thermodilution method yielded values for both absolute anterior regional blood flow and changes in anterior regional flow that compared closely to anterior descending bypass graft flow measured independently. The multithermistor technique may be useful in monitoring flow effects of regional coronary disease over time, as well as in studies of agents purported to alter regional blood flow.

Blood Flow Velocity↗

Effect of sublingual nitroglycerin on regional flow in patients with and without coronary disease.

We evaluated the effects of sublingual nitroglycerin on indices of regional coronary flow and coronary resistance (CR) in 12 selected patients with coronary artery disease (CAD) and eight with normal coronary arteries (NCA), using continuous thermodilution. Resting total left ventricular flow, reflected by coronary sinus flow (CSF), and anterior regional flow, reflected by great cardiac vein flow (GCVF), in NCA and CAD patient groups, were similar. However, in a subgroup of six patients, with CAD limited to the anterior descending artery, GCVF was lower and anterior regional CR (CRANT) higher than the NCA subjects. Nitroglycerin reduced the systolic pressure-heart rate product similarly in both patient groups. CSF and GCVF in NCA subjects declined 15% and 17%, respectively, as total CR (CRT) and CRANT increased. In the CAD subgroup, consisting of patients with CAD limited to the anterior descending, GCVF increased 48% as CRANT declined 50%, and CSF was unchanged. In the other CAD subgroup of patients with CAD in the right and/or circumflex arteries, GCVF declined 32% and CRANT increased 46% as CSF was minimally increased. These data imply that sublingual nitroglycerin reduces both CSF and GCVF in NCA patients as oxygen demands decrease. In certain CAD patients, however, nitroglycerin alters regional coronary venous blood flow, suggesting a redistribution of flow from normally perfused to hypoperfused regions.

Administration, Oral↗

Platelet aggregation in aortic and coronary venous blood in patients with and without coronary disease. 3. Role of tachycardia stress and propranolol.

We studied 16 patients with coronary artery disease (CAD) to evaluate platelet aggregation in blood samples withdrawn simultaneously from the aorta and coronary sinus. At rest, mean platelet aggregation in coronary venous blood was significantly lower than that in aortic blood. Platelet counts in coronary venous blood were also lower than in the aortic blood in each of the six CAD patients in whom counts were done. Platelet aggregation was lower in seven patients who were taking propranolol than in the remaining nine who were not taking propranolol. During tachycardia stress, platelet aggregation increased in all patients, but the magnitude of increase was greater in patients not taking propranolol. In four other patients without CAD, platelet aggregation and counts were also studied in the same fashion and were similar in both the aortic and coronary venous blood. These data suggest that in certain CAD patients, platelet consumption or destruction within atherosclerotic vasculature may occur. Propranolol may reduce platelet aggregation at rest and modify excessive aggregation during tachycardia stress in certain CAD patients.

Aorta↗

Myocardial damage after repetitive direct current shock in the dog: correlation between left ventricular end-diastolic pressure and extent of myocardial necrosis.

Acute myocardial necrosis was produced in 27 anesthetized dogs by repetitive DC 75 joule shock delivered with one electrode in the left ventricular cavity and the other on the left chest wall. A total of 1 shock/kg body weight delivered at 10 sec intervals resulted in discrete anterior wall necrosis of 7% to 31% (mean, 17.6%) of the mass of left ventricular myocardium. After some transient bradycardia, normal sinus rhythm was restored. Depression of left ventricular function 15 min after shock (rise in LVEDP from 4.0 +/- 1.5 to 17 +/- 2 mm Hg and fall in cardiac output from 2.29 +/- 0.24 to 1.82 +/- 0.12 L/min) recovered only slightly during the ensuing 2 hr. A significant correlation (r=0.85) was observed between the LVEDP at 2 hr after shock and the extent of necrosis determined histochemically and histologically at the time of sacrifice 3 hr after shock. Thus, in this form of acute myocardial damage, pump dysfunction is closely related to the area of necrosis.

Animals↗

Dissociation of the neutrophill functions of exocytosis and chemotaxis.

The peptide Gly-His-Gly is shown to be chemotactic for human neutrophils in vitro and for rabbit neutrophils in vivo but to be unable to induce lysosomal enzyme release from human neutrophils at sublytic concentrations. The failure of this chemotactic peptide to elicit lysosomal enzyme release provides evidence that interactions with a chemotactic receptor does not necessarily activate chemotaxis and exocytosis in the human neutrophil, thus suggesting that the presumed common pathway of exocytosis and chemotaxis may be divergent at the cell receptor and/or postreceptor level.

Albumins↗