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Acebutolol (M & B 17,803 A), a new cardioselective beta-adrenergic blocking agent, was given intravenously to 20 selected patients with various cardiac arrhythmias. Cumulative doses ranging from 12.5 to 50 mg were moderately or highly effective in 4 out of 4 patients with sinus tachycardia, 2 out of 3 patients with premature atrial beats, 3 out of 4 patients with premature ventricular beats, 3 out of 5 patients with atrial fibrillation (one was converted to sinus rhythm) and in 2 out of 3 patients with atrial flutter. The drug was ineffective in one patient with atrial tachycardia. Mild systolic hypotension occured in two patients with recent myocardial infarction and there was some aggravation of a preexisting bronchospasm in a patient with congestive heart failure secondary to hyper-thyroidism. It was concluded that acebutolol is a cardioselective beta-blocker which by intravenous route may be useful in the treatment of selected cardiac arrhythmias.

A homogenate from dwarf pea seedlings that had been treated with [(3)H]gibberellin A(1) was separated by Sephadex G-200 into two protein fractions, of high and intermediate molecular weight, with affinity for [(3)H]gibberellin A(1). Neither fraction bound [(3)H]gibberellin A(8), the only metabolite of [(3)H]gibberellin A(1) detected in significant quantity in extracts of pea seedlings. These proteinhormone complexes were noncovalently bound, as evidenced by their rapid disruption in ethanol. Approximate molecular weights of the fractions were 500,000 and 60,000. In experiments designed to detect competition for the binding proteins between [(3)H]gibberellin A(1) and closely related [(3)H]gibberellin molecules, [(3)H]gibberellin A(8) and pseudo [(3)H]gibberellin A(1) were inactive, but keto [(3)H]gibberellin competed favorably. Equilibrium dialysis experiments revealed that both high-molecular-weight and intermediate-molecular-weight protein-hormone complexes could undergo hormone exchange with nonlabeled gibberellin A(1).

The major metabolite produced during incubation of [(3)H]gibberellin A(1) ([(3)H]GA(1)) with barley aleurone layers is an amphoteric, water-soluble compound tentatively called [(3)H]ampho GA(1). Formation of [(3)H]ampho GA(1) in barley aleurones begins after a period of 2.5 hours. As judged by degradation studies as well as Sephadex column chromatography, GA(1) appears to be linked to a peptide; positions C-3 and C-7 were ruled out as conjugation sites.

The relationship between the increase in catecholamine levels of the coronary sinus blood and the amplitude of various cardiac responses to adrenergic nerve stimulation was studied in anesthetized dogs. Plasma catecholamine levels in both coronary sinus and aortic blood were measured by a modification of the radiometric enzymatic assay for tissue catecholamines and were found to be 0.622 plus or minus 0.104 (SE) ng/ml and 0.933 plus or minus 0.116 ng/ml, respectively, under basal conditions. The catecholamine levels in coronary sinus blood increased linearly during right cardioaccelerator nerve stimulation up to a frequency of 10 Hz. At this frequency, maximum values were observed in both coronary sinus blood catecholamine levels and cardiac responses. The correlation between the response in heart rate, mean coronary blood flow, and dP/dt of left ventricular pressure and the increase in endogenous catecholamine levels of coronary sinus blood was significant, but the relationship was nonlinear. The present experimental design may prove to be a reliable means of studying the role of the sympathetic nervous system in the regulation of cardiovascular function in vivo.

Uptake and metabolism of 1,2-[(3)H]gibberellin A(1) ([(3)H]GA(1), I) and its 3-hydroxy epimer ([(3)H]pseudoGA(1), II) by barley (Hordeum vulgare L.) half-seeds were measured after 24 hours of incubation, in the presence or absence of abscisic acid in the media. Uptake of both compounds was enhanced by abscisic acid, and abscisic acid enhanced the extent of metabolism of [(3)H]GA(1). However, [(3)H]pseudoGA(1) was not metabolized, even in the presence of abscisic acid. The significance of the stereo-chemistry of the 3-hydroxyl position is discussed.

When barley aleurone layers were incubated with (3)H-Gibberellin A1 ((3)H-GA1), the hormone was converted to (3)H-GA-X (not identified), (3)H-GA8 and two other compounds tentatively identified as (3)H-GA1-glucoside, and (3)H-GA8-glucoside. Uptake and metabolism of the (3)H-GA1 were markedly enhanced by simultaneous treatment with abscisic acid (ABA). Uptake of (3)H-GA1 from the medium containing ABA was linear over a 24-h period, whereas in the absence of ABA, uptake of (3)H-GA1 leveled off after 5 h. After 24 h, aleurones treated with (3)H-GA1 and (3)H-GA1 plus ABA, had taken up 9 and 24%, respectively, of the original (3)H-GA1 provided. Metabolism of (3)H-GA1 proceeded at a linear rate in the presence of ABA. The amount of (3)H-GA1-metabolites which had accumulated by the end of a 24-h incubation appeared to be linearly correlated to the logarithm of the ABA concentration. Gibberellins A8 and-A8-glucoside did not reverse GA1-enhanced synthesis of α-amylase.

The serum levels of digoxin resulting from the oral administration of 0.25 mg. of Lanoxin and Rougoxin preparations were studied in 12 healthy volunteers by means of a double-blind crossover design. No differences between the two brands could be demonstrated with respect to disintegration time, content uniformity, peak serum levels and cumulative areas under the curve for an eight-hour period.