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Biomedical subjects

R H Goldman

Publications and source records attributed to R H Goldman.

At least 37 records · Page 2Linked to original sources
PubMed1976

Age-related changes in ouabain pharmacology. Ouabain exhibits a different volume of distribution in adult and young dogs.

To better understand why one must administer much higher doeses of digitalis glycosides to immature than to mature humans and animals, we studied ouabain pharmacokinetics in adult and young dogs. Consistent with reported observations that ouabain-binding, metabolism, and excretion do not change with age, we found no significant differences in the transfer coefficients in a linear two-compartment open model for ouabain pharmacokinetics following a bolus of 0.05 mg/kg. We did find, however, that young dogs had nearly twice the ouabain volumes of distribution per kilogram of body weight as adults (155.4 +/- 1.2 (SE) ml/kg vs. 80 +/- 0.6, P less than 0.0005) and that one could account for this difference with the fact that young dogs had nearly twice the plasma volume 108 +/- 9.8, vs. 68 +/- 7.3, P = 0.001) and interstitial fluid space (318 +/- 35 vs. 190 +/- 6.5, P = 0.006) as the adults. For the same dose per kilogram, left and right ventricular ouabain concentrations were inversely related to the volume of distribution, with the adults having significantly higher tissue levels and incidence of arrhythmias. One must give more ouabain to a young dog to get the same plasma concentration as in an adult because the mass of ouabain in rapid equilibrium with the plasma is diluted in a larger volume of distribution.

Aging↗
PubMed1975

Investigation of the safe withdrawal period for propranolol in patients scheduled for open heart surgery.

The time necessary for dissipation of radioactive labelled propranolol and its metabolites and the cardiac effects of this agent in the hearts of patients undergoing open-heart surgery were studied. Isoprenaline produced chronotropic and inotropic responses in atrial muscle in tissue bath studies which were normal 8 to 12 hours after withdrawing propranolol. After the administration of either 25 or 75 muCi of 14C-labelled propranolol, the myocardial tissue concentration declined to insignificant levels between 24 and 28 hours. We conclude that withdrawal of propranolol therapy 24 to 48 hours before cardiac surgery should be acceptable.

Cardiac Surgical Procedures↗
PubMed1975

Studies on magnesium's mechanism of action in digitalis-induced arrhythmias.

The mechanism by which magnesium affects digitalis-induced arrhythmias was studied in dogs with and without beta-receptor blockade. Digoxin was infused at a rate of 2.5mug/kg/min until ventricular tachycardia developed, then half the animals were given MgSO4, the other half saline. In animals given MgSO4, sinus rhythm was immediately re-established; in animals given saline, ventricular tachycardia persisted. In animals with beta-receptor blockade, MgSO4 was as effective in abolishing ventricular tachycardia as in those without beta-receptor blockade. We found no evidence that magnesium re-activated digoxin-inhibited (Na+, K+)-ATPase, altered myocardial or microsomal digoxin binding, or acted via the autonomic nervous system. Magnesium's direct effect on calcium and potassium fluxes across the myocardial cell membrane may be the mechanism of its antiarrhythmic action in digitalis-toxic arrhythmias.

Animals↗
PubMed1975

Hemodynamics, renal function, plasma renin, and aldosterone in man after 5 to 14 days of bedrest.

Continous bedrest for 5 to 14 days had no significant effect on resting heart rate, blood pressure or cardiac output in six normal men. Head-up tilt induced greater tachycardia in 5 of 6 patients after bed rest than in the control period. Propranolol diminished both the tachycardia and the incidence of hypotension and faintness in upright posture. Body weight, serum electrolytes and resting renal plasma flow, and glomerular filtration rate were unchanged by bedrest. Plasma volume fell, extracellular fluid volume increased, and plasma renin activity was significantly elevated following bedrest. Unusually large increases in plasma renin followed head-up tilt or administration of isoproterenol during bedrest, and after resuming normal activity. During bedrest, plasma aldosterone was often increased in the early morning. We conclude that after bedrest, upright posture evokes strong beta-adrenergic activity, with exaggerated metabolic and circulatory responses which can be reduced or abolished by the beta-adrenergic blocker, propranolol.

Adult↗
PubMed1974

Physiological distribution of digoxin in human heart.

Using the recipient's human heart removed at cardiac transplantation, the distribution of digoxin at both the cellular and subcellular level has been studied. In the presence of diffuse histological myocardial abnormalities tissue digoxin is decreased, but the subcellular distribution, presumably reflecting binding to a possible receptor site, is uniform. When the histological abnormality is focal then digoxin distribution is uniform.These results suggest that in the presence of myocardial ischaemia plasma digoxin concentrations may not reflect total myocardial levels accurately.

Adenosine Triphosphatases↗