Biomedical subjects

A M Feldman

Publications and source records attributed to A M Feldman.

At least 127 records · Page 7Linked to original sources

PubMed1988

Evaluation of a new inotropic agent, OPC-8212, in patients with dilated cardiomyopathy and heart failure.

OPC-8212 is a new positive inotrope with a unique mechanism of action. To assess its clinical utility we administered 60 mg/day for 30 days to 10 patients with overt congestive heart failure, who had substantial limitations in exercise performance despite treatment with conventional therapy. Patients were evaluated by simultaneous respiratory gas exchange and radionuclide ventriculography measurements during graded maximal exercise testing. Improvement was demonstrated in both peak oxygen uptake and radionuclide-determined cardiac index after 30 days of treatment with OPC-8212. These changes were not associated with alterations in heart rate at rest or during peak exercise. Furthermore OPC-8212 significantly decreased ventricular ectopy in our patients. However, two patients had possible hematologic toxicity with prolonged use. The results of the present phase II study suggest that a larger randomized double-blind placebo study to evaluate the safety and clinical efficacy of this drug is warranted.

Adult↗

PubMed1988

Pharmacodynamics and tolerance of oral sustained release ritodrine.

A new oral sustained release formulation of ritodrine was tested for patient tolerance in this open study. The doses tested were 120 mg/day, 240 mg/day, and 360 mg/day. No objective toxicity was seen at any level. Doses of 120 mg/day and 240 mg/day were well-tolerated. Of the subjects who received the 360 mg/day dose, most tolerated it well.

Administration, Oral↗

PubMed1988

Congestive cardiomyopathy in patients on continuous ambulatory peritoneal dialysis.

We present a report of cardiac dilatation and symptomatic congestive heart failure in two patients receiving treatment with continuous ambulatory peritoneal dialysis (CAPD). Both patients had previous partial parathyroidectomies and persistent hypocalcemia prior to the development of a congestive cardiomyopathy. The hypocalcemia was unresponsive to treatment with activated vitamin D therapy; however, intravenous replenishment of the ionized serum calcium level was accompanied by improvement in cardiac functional parameters. In one of the two patients, chronic calcium repletion with high dialysate calcium was associated with significant improvement in cardiac symptoms and a decrease in left ventricular dilatation. These observations suggest that partial parathyroidectomy and associated hypocalcemia place patients on CAPD at increased risk of cardiac dysfunction.

Adult↗

PubMed1988

Increase of the 40,000-mol wt pertussis toxin substrate (G protein) in the failing human heart.

Human heart failure is associated with a diminished contractile response to beta-adrenergic agonists. We hypothesized that alterations in the activity of a guanine nucleotide-binding regulatory protein (G protein) might be partially responsible for this abnormality. We therefore measured the activity of G proteins in failing human myocardium utilizing bacterial toxin-catalyzed ADP ribosylation. The activity of a 40,000-mol wt pertussis toxin substrate (alpha G40) was increased by 36% in failing human hearts when compared with nonfailing controls. In contrast, there was no change in the level of the stimulatory regulatory subunit (Gs). The increased activity in alpha G40 was associated with a 30% decrease in basal as well as 5'-guanylyl imidodiphosphate-stimulated adenylate cyclase activity. These data suggest that increased alpha G40 activity is a new marker for failing myocardium and may account at least in part for the diminished responsiveness to beta 1-adrenergic agonists in the failing human heart.

Adenosine Diphosphate Ribose↗

PubMed1987

NAD+-mediated stimulation of adenylate cyclase in cardiac membranes.

NAD+ significantly enhances adenylate cyclase activity in crude cardiac membrane preparations. This increase is dose-dependent, does not occur in the presence of nicotinamide, ADP-ribose or NADP+, and can be effected by a 30 min pre-incubation period with NAD+. Time course studies are consistent with an enzymatically mediated modification that used NAD+ as substrate. Furthermore, inhibition of NAD+-mediated activation by arginine suggests that this modulation of cardiac adenylate cyclase is analogous to that catalyzed by endogenous ADP-ribosyl transferases.

Adenosine Diphosphate Ribose↗

PubMed1987

Negative inotropic effects of furosemide in the isolated rabbit heart: a prostaglandin-mediated event.

Furosemide is an effective diuretic that initiates a rapid diuresis and peripheral vasodilatation through renal adenylate cyclase inhibition and prostaglandin synthesis. Recently, it has been shown to be associated with activation of the neurohumoral vasoconstrictor mechanism and a further compromise of left ventricular function in patients with heart failure. The present study was performed to investigate the direct effects of furosemide on myocardial performance in the isolated perfused rabbit heart. Furosemide (10(-3) M) caused a significant decrease in developed pressure as well as a similar fall in coronary perfusion pressure. Furosemide also decreased myocardial contractility when the coronary perfusion pressure was kept constant. The change in developed pressure but not the decrease in coronary perfusion pressure could be blocked by treatment with indomethacin. Furosemide did not antagonize rabbit cardiac membrane adenylate cyclase. Therefore, furosemide has a direct inhibitory effect on cardiac contractility that is related to prostaglandin synthesis.

Adenylyl Cyclases↗

PubMed1987

Functional and metabolic consequences of vitamin B-6 deficiency in the rat heart.

The cardiac functional and metabolic consequences of pyridoxine deficiency were studied in rats maintained on a pyridoxine-deficient diet for 10 weeks. Because food intake was diminished in the pyridoxine-deficient rats, a second group of animals was fed a diet restricted to the intake of the pyridoxine-deficient animals. The inotropic response (developed pressure) to an isoproterenol or Ca2+ concentration response curve was measured simultaneously with high energy phosphate levels using a modified Langendorf apparatus and 31P nuclear magnetic resonance spectroscopy. The inotropic response to Ca2+ and isoproterenol was significantly decreased relative to controls in both the food-deprived and the pyridoxine-deficient groups. Developed pressure after adrenergic stimulation was significantly less in the pyridoxine-deficient than in the food-deprived animals. Phosphocreatine and ATP levels were maintained and did not differ among the control, pyridoxine-deficient, and food-deprived groups during isoproterenol and Ca2+ stress, implying that the diminished inotropy was not due to an abnormality in generation of high energy phosphate levels.

Adenosine Triphosphate↗

PubMed1986