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Dynamics of circulating catecholamines (CA) were studied at rest (heart rate = 104 +/- 3 beats/min) and during mild treadmill exercise (heart rate = 168 +/- 5 beats/min) in 60 dogs. Plasma epinephrine (E) and norepinephrine (NE) removal from circulation and release into circulation were estimated from plasma CA arteriovenous differences across the regional vascular beds studied (pulmonary, myocardial, hepatosplanchnic, renal, and skeletal muscle vascular beds) and from regional blood flows. Regional plasma E fractional extraction (PEFE) was used as an index of NE removal from plasma. Arterial plasma CA increased significantly from rest to exercise (P less than 0.05). A significant PEFE was observed at rest and exercise across all studied vascular beds but the pulmonary bed. When plasma flow was taken into account, the largest contributors to plasma CA removal were the hepatosplanchnic vascular bed at rest and skeletal muscle vascular beds during exercise. At rest, the hepatosplanchnic vascular bed was a major contributor to the plasma NE pool. During exercise, main contributors to NE release into plasma were skeletal muscle vascular beds. Circulating CA kinetics did not appear to vary from rest to exercise. Clearance and apparent distribution space were estimated to be, respectively, 1.5 l/min and 2 liters for circulating E and 2 l/min and 5 liters for NE at rest and exercise. Circulating E and NE half times were estimated to be approximately 1 and 1.8 min, respectively.

Coronary sinus catecholamine overflow was measured in open-chest dogs, anesthetized with sodium thiopental and alpha-chloralose, during left sympathetic stimulation. Uniform ventricular tachycardias were induced in 9 out of 16 dogs during either left stellate ganglion or left ventrolateral cardiac nerve stimulations. Significant increases in norepinephrine (8.1 ng/mL, plasma) and epinephrine (0.19 ng/mL, plasma) overflows were obtained after 30 and 90 s of stimulation, respectively. Maximum norepinephrine overflow was significantly higher in dogs with ventricular tachycardia than in those without it (16.0 vs. 7.4 ng/mL, p less than 0.05). This suggests that the induction of ventricular tachycardia in the normal myocardium is related to the amount of local secretion of norepinephrine during nerve stimulation.

Correlations between the concentration of endogenous catecholamines in coronary sinus blood and various physiological responses to adrenergic stimulation were studied in anesthetized dogs. Plasma catecholamine levels both in coronary sinus and aortic blood were measured by means of a modification of the radiometric-enzymatic assay for tissue catecholamines, and found to be 0.769 +/- 0.110(S.E.) and 0.972 +/-0.127(S.E.) ng/ml, respectively, under basal conditions. Circulating catecholamine levels increased after the intracoronary injection of 6-hydroxydopamine, which has an indirect sympathomimetic action. Both the increment in catecholamine release from the heart and the intensity of physiological response were dose-related. A frequency-dependent increase in coronary sinus blood catecholamine levels occurred during right cardioaccelerator nerve stimulation. Maximum values were observed with a stimulation frequency of 10 Hz, at which maximum physiological responses were obtained. A highly significant correlation was found between endogenous catecholamine levels in coronary sinus blood and the dp/dt of left ventricular pressure (r = 0.750, p less than 0.001), as well as mean coronary blood flow (r =0.706, p less than 0.001). The present preparation may prove to be a reliable means of studying the role of the sympathetic system in regulating cardiac function.

Direct injection of amiodarone (10-1000 micrograms) into the sinus node artery of the isolated blood-perfused dog atrium produced dose-dependent negative inotropic and chronotropic responses that were unaffected by atropine. Intraarterial amiodarone also had a negative inotropic action on isolated left ventricular muscle preparations electrically paced at 1.5 to 2.0 Hz. A continuous infusion of 100 micrograms/min of amiodarone significantly suppressed the positive chronotropic effect of norepinephrine whether expressed in percent change or in absolute values; its positive inotropic effect expressed in percent change was not suppressed but rather enhanced by amiodarone. Calcium chloride induced positive chronotropic and inotropic effects expressed in percent change were, respectively, slightly suppressed and enhanced by amiodarone. Intravenous injection of amiodarone (5 mg/kg) decreased the heart rate and blood pressure of the support dog and produced a negative inotropic response in the isolated left ventricular muscle preparation perfused with arterial blood from the support dog. These results suggest first, that amiodarone has direct negative inotropic and chronotropic effects that are not mediated by cholinergic mechanisms and second, that it has a depressive action on norepinephrine and calcium-induced positive chronotropic effects and an enhancing action on their positive inotropic effects.

Various biochemical, pharmacologic, and physiologic techniques were used to evaluate the sympathetic tone and reactivity in labile and sustained hypertension in humans. The results of these studies suggest the existence of an important subgroup of hypertensive patients characterized by increased basal sympathetic tone and reactivity to standing. Such abnormalities could be the result of various dysfunctions, involving the activity of central and peripheral cardiovascular sympathetic fibers, the presynaptic modulation of sympathetic fibers (including the interaction with the parasympathetic system), the inactivation of circulating norepinephrine, and the sensitivity of the efferent cells. The increase in circulating norepinephrine in a group of hypertensive patients seems to reflect a functional increase in the sympathetic tone as shown by the presence of hyperkinetic cardiac functions in hyperadrenergic patients (elevated catecholamine levels), while cardiac functions are normal in normoadrenergic patients (catecholamine levels within normal range). Moreover, the better hypotensive response, combined with normalization of the basal and reactive circulating norepinephrine levels following beta-blockade in hyperadrenergic hypertensive patients, strongly supports the participation of the sympathetic system in the maintenance of hypertension in those patients. The identification and characterization of this subpopulation of patients may be helpful in the development of more rational therapeutic approaches and could eventually permit us to devise better predictors of outcome in hypertension.

The purpose of this study was to describe plasma atriopeptin concentrations at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) performed with or without nonspecific beta-adrenergic blockade (1 mg/kg iv propranolol) in 10 mongrel dogs [19 +/- 2 (SE) kg]. A small (20%) but significant (P less than 0.05) increase in plasma atriopeptin concentration was observed from rest (43 +/- 5 pg/ml) to exercise (52 +/- 6 pg/ml) without beta-blockade. Propranolol significantly reduced heart rate at rest (89 +/- 7 vs. 104 +/- 7 beats/min) and during exercise (96 +/- 10 vs. 176 +/- 11 beats/min), and this was associated with a larger increase in plasma atriopeptin concentration during exercise (rest 46 +/- 6 pg/ml; exercise 171 +/- 22 pg/ml). Exercise under beta-blockade is associated with an increased preload of the heart. These results further support the hypothesis that atriopeptin release during exercise is under the control of atrial stretch. The higher plasma atriopeptin concentration observed during exercise under beta-blockade may contribute to the reduction of the response of plasma renin activity (1.0 +/- 0.1 vs. 3.0 +/- 0.6 ng.ml-1.h-1) and aldosterone concentration (87 +/- 36 vs. 138 +/- 25 pg/ml). Vasopressin concentration was lower at rest and during exercise under propranolol (3.5 +/- 1.3 vs. 4.9 +/- 0.9 and 6.1 +/- 2.2 vs. 9.9 +/- 1.5 pg/ml, respectively), which might reflect a dissociation between activity of the renin-angiotensin system and vasopressin release.

1. The effects of DA2 agonist, quinpirole (50 micrograms/kg, i.v.) and a DA2 antagonist, domperidone (50 micrograms/kg, i.v.) on the release of adrenal catecholamines were evaluated in the anaesthetized and vagotomized dog. 2. Stimulations (5 V pulses of 2 ms duration for 3 min) of the splanchnic nerve at frequencies of 1, 3 and 5 Hz were applied randomly before and after injection of the drug. 3. The results show that quinpirole reduces significantly the release of adrenaline at 1 and 3 Hz but not at 5 Hz, while the release of noradrenaline is reduced at 1 Hz but not at 3 and 5 Hz. Inversely, domperidone potentiates significantly the release of both catecholamines at 3 and 5 Hz, but not at 1 Hz. 4. There was no change in basal release of adrenal catecholamines, adrenal blood flow or heart rate after both drug treatments. 5. The mean arterial pressure was not affected by domperidone treatment but there was a significant reduction in basal mean arterial pressure after the injection of quinpirole. 6. There was no change in any of these parameters during electrical stimulation. 7. Therefore, these results strongly suggest that DA2 dopamine receptors are present at the level of the adrenal medulla and that their activation could mediate an inhibitory modulation on the adrenal catecholamines release within a certain range of electrical stimulation.

Plasma catecholamine (CA; picograms per millilitre) concentrations were measured simultaneously with heart rate (HR, beats per minute) during short-duration exercise, and with plasma glucose, lactate, and free fatty acid (FFA) concentrations (millimoles per litre) during long-duration exercise, in control dogs (N-dogs) and in sympathectomized dogs (S-dogs) with 6-hydroxydopamine (50 mg X kg-1). At rest, higher plasma CA in S-dogs (690 +/- 90 vs. 320 +/- 60) was associated with higher HR (126 +/- 3 vs. 90 +/- 5), plasma glucose (6.4 +/- 0.2 vs. 5.1 +/- 0.2), lactate (2.9 +/- 0.2 vs. 1.6 +/- 0.2), and FFA concentrations (1.08 +/- 0.11 vs. 0.81 +/- 0.11). During short-duration exercise a normal HR response in S-dogs (226 +/- 9 vs. 228 +/- 8) was dependent upon larger than normal plasma CA values (4280 +/- 680 vs. 1990 +/- 360). Metabolic adjustments to long-duration exercise were impaired in S-dogs as evidenced by the higher plasma glucose and lactate concentrations (8.2 +/- 0.5 and 5.5 +/- 0.3 vs. 6.4 +/- 0.4 and 4.6 +/- 0.3) and the lower plasma FFA concentration (0.66 +/- 0.16 vs. 1.20 +/- 0.09). These occurred despite a normal plasma CA response in S-dogs (6850 +/- 1450 vs. 8740 +/- 1680). Following chemical sympathectomy the adrenal medulla can compensate to ensure an adequate heart rate response to short-duration exercise, but not to ensure adequate metabolic adjustments to prolonged exercise.

To investigate ventricular tachycardias produced in healthy canine myocardium by stimulation of sympathetic ganglia or cardiac nerves, we simultaneously recorded a surface ECG and 63 ventricular electrograms in anesthetized open-chest dogs. Isochronal and isopotential maps were generated off-line by computer. Ventricular tachycardia with uniform beat-to-beat morphology was induced in 13 or 22 dogs by electrical stimulation of the left stellate ganglion (five experiments), the left middle cervical ganglion (four experiments), the left caudal pole cardiopulmonary nerve (two experiments), or the ventrolateral cardiac nerve (eight experiments). It was not inducible by stimulation of the right-sided major cardiopulmonary nerves or ganglia. In most instances the earliest measured electrical excitation occurred on the posterior aspect of the ventricles. Isochronal maps demonstrated a radial spread of the impulse away from the area of earliest excitation. Changes in the region of earliest excitation and (or) activation pattern were accompanied by changes in QRS morphology. The potential gradients measured between areas displaying positive and negative T waves on the anterior and left lateral aspects of the ventricles were significantly increased by ventrolateral cardiac nerve stimulation. However, the ventricular regions where these potential gradients existed differed from the regions of earliest excitation during ventricular tachycardia. These results demonstrate that the thoracic autonomic nervous system can induce repetitive ventricular excitation originating from consistent loci.

Circulating catecholamine (CA) levels in the aortic blood did not change significantly in anesthetized dogs during a period of 60 min following the rapid intravenous injection of ouabain at a dose of 10 microgram/kg, but they did increase significantly after administration of a dose of 75 microgram/kg. After bilateral cervical vagotomy, the high dose of ouabain caused a greater and earlier elevation in circulating CA levels than in intact animals along with an increased cardiac index and a lower peripheral resistance. These findings suggest the existence of a vagal inhibitory mechanism upon liberation of CA following the administration of ouabain. Although ventricular arrhythmias did occur before the increase in circulating CA, preinjection CA levels were significantly higher in animals presenting ventricular fibrillation, suggesting that a high background adrenergic tone facilitates the production of ventricular arrhythmias by ouabain. Moreover, ventricular tachycardia occurred earlier in vagotomized dogs, in which the immediate elevation of circulating CA could have been a precipitating factor for this type of arrhythmia.

Vectorcardiograms (VCGs) of 44 patients with a Wolff-Parkinson-White (WPW) syndrome have been analyzed with the aim to correlate the QRS loop patterns with specific preexcitation sites. The VCG QRS loops were analyzed to determine whether conduction abnormalities and myocardial infarction (MI)-like patterns observed in the WPW syndrome could be related to specific preexcitation sites identified by surgery as well as by body surface potential mapping (BSPM). Left bundle branch block pattern was observed with anteroseptal (AS) preexcitation, anterior MI pattern was seen with lateral right ventricle (LRV) preexcitation, left anterior fascicular block was observed with posterior right ventricle (PRV) preexcitation, inferoposterior and strictly posterior MI pattern was found with posteroseptal (PS) and posterior left ventricle (PLV) preexcitation, right bundle branch block was seen in lateral left ventricle (LLV) preexcitation, and right bundle branch block was observed with left posterior fascicular block in anterior left ventricle (ALV) preexcitation. These VCG criteria seem to identify accurately the preexcitation sites as observed by delta wave BSPM and at surgery investigations. Consequently, they could be useful in localizing the preexcitation site in cases of ambiguous delta vector orientation.

Anterograde and retrograde pathways are the two major components of the reentry circuit in patients with paroxysmal supraventricular reentrant tachycardias. Therefore, the capacity of each pathway to maintain 1:1 conduction would be expected to determine the cycle length (CL) of the tachycardia. In this study, the possible relationship between the CL of reentrant tachycardia and the maximum capacities of anterograde and retrograde conduction in the maintenance of a 1:1 response during atrial and ventricular pacing were examined. This relationship was analyzed in 26 patients with orthodromic reentrant tachycardia due to Wolff-Parkinson-White syndrome (group 1) and compared with that in 26 patients with atrioventricular nodal reentrant tachycardia (group 2). There were no statistically significant differences between the two groups in the shortest tachycardia CLs (mean +/- SD, 325 +/- 44 versus 329 +/- 52 ms); in the shortest ventricular pacing CLs with 1:1 response (314 +/- 63 versus 319 +/- 38 ms); nor in the CLs that produced retrograde atrioventricular block (306 +/- 62 versus 301 +/- 37 ms). In contrast, the longest atrial pacing CL that produced Wenckebach's phenomenon and the shortest atrial pacing CL with 1:1 response were significantly shorter for group 1 than for group 2 patients (290 +/- 38 versus 390 +/- 88 ms, P less than 0.001) and (305 +/- 38 versus 406 +/- 90 ms, P less than 0.001), respectively. It was concluded that the CL of orthodromic tachycardia can best be predicted from the shortest atrial pacing CL that maintains 1:1 anterograde conduction via the normal pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the relationship between the effects of lidocaine on excitation patterns and its effects on the incidence of arrhythmias, the left anterior descending coronary artery was occluded for 6-min periods separated by 30 min of reperfusion, under control conditions and after injection of lidocaine, at a dose of either 2.5, 5.0, or 10.0 mg/kg i.v., in 29 open-chest anesthetized pigs. Sixty-three unipolar electrograms and a surface lead electrocardiogram were continuously recorded during atrial pacing and spontaneous ventricular arrhythmias. Ventricular fibrillation (VF) occurred only in four of a total of 45 control occlusions. VF occurred in two of five pigs following injection of lidocaine 2.5 mg/kg, in 15 or 17 pigs following injection of a 5 mg/kg dose, and in all three preparations following injection of a 10 mg/kg dose. Just prior to VF during occlusions preceded by injections of lidocaine 5 mg/kg, activation time of ischemic myocardium in atrial-paced beats was delayed by only 30 +/- 17 ms beyond preocclusion values, compared with 18 +/- 11 ms at a similar time during control occlusions and 33 +/- 18 ms at the end of control occlusions (mean +/- SD; n = 8). As ventricular tachycardia (VT) developed in the presence of lidocaine, conduction was further slowed or blocked in ischemic areas, and slowed in nonischemic regions; at the transition from VT to VF, excitation patterns displayed circus movement involving nonischemic regions.

Isoarea maps during the PQRST sequence were computed in 22 healthy subjects and 48 patients with Wolff-Parkinson-White (WPW) syndrome. Thirty-eight patients with WPW were on no medication and 10 were treated with class I, II, or III antiarrhythmic drugs. Seventeen isoarea maps were recorded before and 17 were recorded after accessory pathway ablation. One patient had intermittent preexcitation. Body surface maps from all healthy subjects were similar, although the magnitudes of the maxima and minima showed significant variability. In all patients with WPW who were on no medication and in those on class I and II agents, PQRST maps were normal. Two patients taking amiodarone had abnormal PQRST maps, as did patients early after surgery. In the patient with intermittent preexcitation, PQRST maps were very similar during normal and preexcited beats. In conclusion, our results support the theory that the PQRST time integral reflects intrinsic recovery properties of the heart and is independent of the activation sequence.

We investigated the possibility that the prolongation of the ventricular effective refractory period (VERP) by amiodarone might be mediated, at least in part, by inhibition of thyroid influence on the heart. VERP values were measured in vitro in isolated septal preparations obtained from control, thyroidectomized and thyroxine (tetraiodothyronine; T4)- or triiodothyronine (T3)-treated rats. Differences in thyroid influence on the heart between these groups were assessed by changes in the myosin isozyme (V1, V2, V3) pattern. VERP measurements were also done in similar groups treated with amiodarone for 7 days (50 mg/kg/day i.p.). VERP tended to be increased by thyroidectomy and was significantly reduced by T4 or T3 treatment when compared with the control group. Amiodarone treatment significantly prolonged VERP in control (33.4 +/- 1.9 to 45.0 +/- 4.5 msec), thyroidectomized (39.9 +/- 1.7 to 48.3 +/- 2.8 msec), T4-treated (26.2 +/- 1.0 to 37.4 +/- 1.3 msec) and T3-treated rats (25.6 +/- 1.1 to 34.3 +/- 1.3 msec). However, the magnitudes of the VERP prolongation by amiodarone were not significantly different among the four groups. The action of amiodarone on action potential duration was similar to its action on VERP. The myocardial concentrations of amiodarone and desethylamiodarone were not significantly different among the four groups. Amiodarone treatment produced a significant reduction of serum T3 levels in the control and in the T4-treated groups and an increase in reverse T3 levels. Thus, the class III action of amiodarone was not affected, in the present model, by experimental modification of thyroid influence on the heart.

In 35 subjects with typical or atypical angina and/or documented myocardial infarction (MI), body surface potential maps (BSPMs), ECG, VCG and rest Thallium-201 (T1-201) have been compared to left ventriculography (LVG). BSPMs were recorded with 26 ECGs, and BSPM abnormalities for MI cases were considered to be areas of normally positive potentials that have become negative. Subjects with MI were classified according to the segmental localization and degree of asynergy on LVG. Moderate anterolateral and apical asynergy were found to correlate with BSPM diagnosis of anterolateral MI and ischemia, severe anterolateral and apical asynergy with BSPM diagnosis of anterolateral MI and ischemia, and moderate diaphragmatic and/or posterobasal asynergy with BSPM diagnosis of posterior MI. Simultaneous anterior and posterior asynergy were found for BSPM diagnosis of anterior with posterior MI. Subjects with no LVG asynergy had normal BSPMs. BSPM diagnosis had the highest correlation coefficient with the LVG diagnosis (r = 0.88). ECG and VCG showed similar results with r = 0.65 and 0.71 respectively, while T1-201 had r = 0.55. The examination of our BSPMs, as well as the ECG, VCG and T1-201, did not permit to detect apical damage in presence of anterior MI, and posterobasal damage in the presence of inferoposterior MI. It is concluded that BSPMs are slightly superior to ECG and VCG for diagnosis of MI.

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.

Both verapamil and diltiazem are used to control ventricular response during atrial fibrillation (AF). Their effect on the maintenance of AF is not known. The effects of the intravenous and oral administration of verapamil and diltiazem were investigated in 35 patients, 18 with (group I) and 17 without (group II) documented paroxysmal AF. Programmed electrical stimulation, either extra-stimuli or burst atrial pacing, was used to induce AF. In group I, the mean values of the duration of AF before and after the intravenous and oral administration of the calcium antagonists were 31 +/- 12, 112 +/- 49 and 69 +/- 25 minutes, respectively. For group II, the values were 5 +/- 3.4, 39 +/- 13 and 14 +/- 7 minutes, respectively. The differences were statistically highly significant (p less than 0.001), after both oral and intravenous administration compared with the baseline value in both groups. The data suggest that both intravenously and orally administered calcium antagonists enhance sustenance of electrically induced AF, especially in patients with spontaneous arrhythmia. Thus, in patients with paroxysmal AF, verapamil or diltiazem should be administered cautiously, because these drugs may prolong the duration of arrhythmia. Further studies are warranted to investigate the role of calcium antagonists in spontaneously occurring paroxysmal AF.

Amiodarone is a potent class III antiarrhythmic agent that has a slow onset of action in patients (ca. 20 days). To determine if myocardial accumulation of desethylamiodarone (DEA), its main metabolite, influences its antiarrhythmic activity, three groups of six Wistar rats were given amiodarone, 50 mg/kg/day i.p. (A groups), and three groups received the same dose of amiodarone in combination with 80 mg/kg/day of phenobarbital to induce hepatic biotransformation (AP groups). After 3, 7 or 21 days, the rats were sacrificed and the ventricular effective refractory period (VERP) was determined by the extrastimulus technique in endocardial preparations superfused in the tissue bath. Control measurements of VERP were done in untreated rats. Myocardial concentrations of DEA measured by high-performance liquid chromatography were significantly higher in the AP groups than in the A groups (7.5 +/- 0.83 vs. 2.27 +/- 0.11 micrograms/g at 3 days, 6.09 +/- 0.70 vs. 2.82 +/- 0.30 micrograms/g at 7 days and 11.93 +/- 1.22 vs. 4.79 +/- 1.84 micrograms/g at 21 days: mean +/- S.E.). Control VERP value was 33.4 +/- 1.2 msec and was increased by 9, 35 and 42% after 3, 7 and 21 days in the A groups, and by 9, 38 and 39% in the AP groups. After 7 days of DEA administration yielding myocardial concentrations similar to those obtained after amiodarone treatment, there was a slight but nonsignificant prolongation of the VERP (12%). Thus, the prolongation of VERP after amiodarone administration did not appear to depend on myocardial DEA accumulation, suggesting that the slow onset of amiodarone class III action may not be related to DEA disposition.

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.