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Biomedical subjects

D W Harron

Publications and source records attributed to D W Harron.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effects of tocainide enantiomers on experimental arrhythmias produced by programmed electrical stimulation.

The enantiomers of tocainide, a Class Ib antiarrhythmic agent, have recently been shown to exhibit differences in antiarrhythmic activity and pharmacokinetic characteristics. The present study examined the antiarrhythmic and electrophysiological effects of SR tocainide, S tocainide, and R tocainide on arrhythmias in a conscious canine arrhythmia model and compared the results with placebo. Using up to three extrastimuli, programmed electrical stimulation was performed in conscious dogs, 7-30 days after coronary artery ligation. Each treatment was assessed for its ability to abolish sustained ventricular tachycardia, prevent nonsustained ventricular tachycardia, and protect against death (ventricular fibrillation), in groups of six dogs. In the placebo group, arrhythmias in four of six dogs remained unchanged, and two dogs died. SR tocainide prevented the arrhythmia in three of six dogs (mean effective dose, 21.3 mg/kg), one remained unchanged, and two died. S tocainide prevented the arrhythmia in four of six dogs (mean effective dose, 7.1 mg/kg), one remained unchanged, and one died (p less than 0.05 compared with placebo). R tocainide prevented the arrhythmia in five of six dogs (mean effective dose, 9.0 mg/kg), one remained unchanged, and none died (p less than 0.01 compared with placebo). PR intervals, QRS durations, and corrected QT intervals were unaffected by any treatment and there was no change in effective or functional refractory periods. These results indicate that the enantiomers of tocainide are more effective than the racemic mixture in abolishing ventricular arrhythmias and in preventing death in this model; no additive antiarrhythmic effect occurs with the racemic mixture, and adverse effects may be potentiated.

Animals↗
PubMed1987

Baroreceptor function in man following peripheral alpha 1- and alpha 2-adrenoceptor stimulation.

Methoxamine and alpha-methyl-noradrenaline were administered to six healthy male subjects on separate days as rapid bolus injections until blood pressure increased by approximately 30 mmHg; Valsalva's Manoeuvre was carried out on each occasion. Propranolol (80 mg) or placebo was administered (random order, double-blind, weekly intervals) and the observations were repeated after 2 h. Baroreceptor sensitivity (delta R-R interval ms/mmHg systolic BP) was less (p less than 0.05) with alpha-methyl-noradrenaline than methoxamine. Propranolol abolished the differences in baroreceptor-mediated bradycardia following alpha-methyl-noradrenaline and methoxamine, and shifted the baroreceptor sensitivity regression lines (p less than 0.05) to the left. During the release phase of Valsalva's Manoeuvre baroreceptor sensitivity was increased following propranolol. The smaller baroreceptor-mediated bradycardia response observed with alpha-methyl-noradrenaline does not support the hypothesis that pre-synaptic alpha-adrenoreceptors have a physiological role in the modulation of baroreceptor function in man, and may be due to alpha-methyl-noradrenaline having beta 1-agonist activity.

Adrenergic alpha-Agonists↗
PubMed1987

Computerized evaluation of Valsalva's Maneuver before and during alpha-adrenoceptor blockade with alfuzosin.

Methodological differences exist in the evaluation of Valsalva's Maneuver. Linear and nonlinear mathematical models were described for beat-to-beat changes in blood pressure and R-R intervals occurring during the strain and release phases of Valsalva's Maneuver. This study indicated that the strain phase is linear, whereas the release phase is nonlinear; the release phase consists of a "lag phase," a "breakpoint," and an "overshoot phase." The alpha-adrenoceptor antagonist, alfuzosin, reduced baroreflex-mediated tachycardia during the strain phase and prolonged the "time lag" and "pressure lag" during the release phase; the latter change was due entirely to the reduced systolic pressure that occurred with alfuzosin at the end of the strain phase.

Adrenergic alpha-Antagonists↗
PubMed1987

The assessment in man of the beta-adrenoceptor blocking activity and cardioselectivity of H-I 42 BS, a long acting beta-adrenoceptor blocking drug.

The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man.

Adrenergic beta-Antagonists↗
PubMed1987

Propranolol disposition in patients with hepatosplenic schistosomiasis.

Eight Sudanese patients with hepatosplenic schistosomiasis and seven Sudanese controls were administered a single oral dose of long acting (LA), propranolol 160 mg; blood propranolol levels were measured at regular intervals for 12 h using g.l.c. In patients with hepatosplenic schistosomiasis, propranolol blood concentrations were greater (P less than 0.05) at all time intervals, Cmax 63.5 (29-143) ng ml-1 (median and range) than controls Cmax 23 (12-37) ng ml-1. Median AUC0-12 was also greater (P less than 0.05) (533 and 218 ng ml-1 h respectively), tmax were not significantly different. In patients and controls prior to treatment, standing heart rate (77.5 (60-110), 72 (68-74) beats min-1) systolic (120 (105-150), 110 (100-120) mm Hg) and diastolic blood pressure (75 (60-90), 70 (60-80) mm Hg) were not significantly different. However following propranolol administration a reduction (P less than 0.05) occurred in both systolic (median 20 mm Hg) and diastolic (median 12.5 mm Hg) blood pressure in the patients compared with controls. Heart rate was reduced by a median of 10 beats min-1 in both groups. These observations indicate that propranolol bioavailability in patients with hepatosplenic schistosomiasis is increased possibly due to reduced presystemic extraction.

Adolescent↗
PubMed1987

Clinical pharmacokinetics of beta-adrenoceptor antagonists. An update.

The beta-adrenoceptor antagonists have been widely used clinically for over 20 years and their pharmacokinetics have been more thoroughly investigated than any other group of drugs. Their various lipid solubilities are associated with differences in absorption, distribution and excretion. All are adequately absorbed, and some like atenolol, sotalol and nadolol which are poorly lipid-soluble are excreted unchanged in the urine, accumulating in renal failure but cleared normally in liver disease. The more lipid-soluble drugs are subject to variable metabolism in the liver, which may be influenced by age, phenotype, environment, disease and other drugs, leading to more variable plasma concentrations. Their clearance is reduced in liver disease but is generally unchanged in renal dysfunction. All the beta-adrenoceptor antagonists reduce cardiac output and this may reduce hepatic clearance of highly extracted drugs. In addition, the metabolised drugs compete with other drugs for enzymatic biotransformation and the potential for interaction is great, but because of the high therapeutic index of beta-adrenoceptor antagonists, any unexpected clinical effects are more likely to be due to changes in the kinetics of the other drug. Because satisfactory plasma concentration effect relationships have been difficult to establish for most clinical indications, and little dose-related toxicity is seen, plasma beta-adrenoceptor antagonist concentration measurement is usually unnecessary. The investigation of the clinical pharmacokinetics of the beta-adrenoceptor antagonists has added greatly to our theoretical and practical knowledge of pharmacokinetics and made some contribution to their better clinical use.

Adrenergic beta-Antagonists↗
PubMed1987

Propafenone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in the treatment of arrhythmias.

Propafenone is a Class I antiarrhythmic agent with weak beta-adrenoceptor antagonist activity which can be given both intravenously and orally. Dosage must be individualised because of dose-dependent pharmacokinetics, a wide range of clinically effective plasma concentrations (64 to 3271 micrograms/L) after comparable doses, the presence of an active metabolite (5-hydroxy-propafenone) and genetically determined metabolic oxidation. In non-comparative studies propafenone 450 and 900 mg/day orally significantly suppressed premature ventricular complexes and couplets in 96% and 75% of patients, respectively, and abolished ventricular tachycardia in 75% of patients. Efficacy was confirmed in placebo-controlled studies in which propafenone 300 to 900mg daily suppressed premature ventricular complexes (greater than 80%) in 77% of patients; 87% of patients had significant reductions in couplets and abolition of ventricular tachycardia. In patients with ventricular arrhythmias refractory to other antiarrhythmic agents, propafenone 450 to 1200 mg/day suppressed arrhythmias in 63% of patients (in long term therapy 66%). Electrically induced arrhythmias were prevented by intravenously administered propafenone in 12 to 23% of patients. However, long term oral therapy was effective in 77% of patients selected using programmed electrical stimulation. Propafenone was also effective in suppressing atrial and AV nodal/junctional re-entrant tachycardias and Wolff-Parkinson-White tachycardias involving accessory pathways. A limited number of comparisons with other antiarrhythmic drugs indicate that the antiarrhythmic efficacy of propafenone is superior or similar to that of quinidine, disopyramide and tocainide, and comparable to that of lignocaine (lidocaine), flecainide and metoprolol against ventricular arrhythmias and a smaller number of atrial arrhythmias. Cardiovascular side effects indicate a proarrhythmic effect similar to that with other Class I drugs, occasional precipitation of congestive heart failure and conduction abnormalities; the latter two occur more often in patients with underlying ventricular dysfunction. Non-cardiovascular side effects (neurological, gastrointestinal) are well tolerated and generally resolve with continued therapy or dosage reduction. Thus, propafenone is an effective antiarrhythmic agent, and is a useful addition to currently available drugs, although further studies will be required to determine clearly its place in therapy compared with more established antiarrhythmic drugs.

Arrhythmias, Cardiac↗
PubMed1986

Experimental evidence for the antiarrhythmic action of indoramin.

The effects of indoramin on cardiac conduction and its antifibrillatory action were investigated and compared with those of mexiletine (class I antiarrhythmic agent), sotalol, and prazosin. In isolated guinea pig atria, indoramin 1 microgram/ml reduced spontaneous rate by 31 +/- 1.0% (mean +/- SE, n = 6) and maximal driving frequency by 25 +/- 1.2% (n = 4). Mexiletine 3 micrograms/ml reduced maximal driving frequency by 35 +/- 1.4% (n = 4) but reduced spontaneous rate by only 13 +/- 2.0% (n = 4). In isolated, perfused, electrically driven (2.5 Hz) guinea pig hearts, indoramin 1 microgram/ml increased the ST interval by 22 +/- 1.9% (n = 6) with no effect on the QRS interval. Higher concentrations (3 micrograms/ml) also increased the QRS interval by 21 +/- 4.0%. In anaesthetized cats, indoramin 6 mg/kg i.v. (infused over 30 min) reduced systolic blood pressure by 36 +/- 3.6% (n = 6) and heart rate by 35 +/- 2.2%, and increased the ST interval by 31 +/- 5.3% and the effective refractory period by 45 +/- 3.2% but had little or no effect on the QRS interval (12 +/- 2.9%) and diastolic electrical stimulation threshold (7 +/- 6.8%). Indoramin 10 mg/kg increased the QRS interval and diastolic electrical stimulation threshold by 20 +/- 2.8 and 23 +/- 2.5%, respectively. Analogous experiments with mexiletine 15 mg/kg showed little changes in cycle length (7 +/- 1.3%), effective refractory period (21 +/- 2.8%), and the ST interval (6 +/- 2.5%); however, there was a marked increase in diastolic threshold (91 +/- 8.9%). Sotalol 15 mg/kg had a cardiac profile similar to that of indoramin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Dose independent pharmacokinetics of mexiletine in healthy volunteers.

In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

Administration, Oral↗
PubMed1985

Antifibrillatory properties of alinidine after coronary artery occlusion in rats.

Ligation of the left anterior descending coronary artery was performed in open-chest anaesthetized rats and mortality as well as changes in ECG were evaluated for 30 min thereafter. Saline or drugs were administered 15 min prior to ligation. In the control group, following a 4 min lag period ventricular arrhythmias as single ectopic beats, ventricular tachycardia and ventricular fibrillation (VF) appeared, reaching a maximum between 10 and 20 min and disappearing after 30 min. Mortality (40% in the control group) coincided with the period of maximal arrhythmias, with VF more common in animals that died than in those surviving. Alinidine, a drug which reduces sino-atrial rate specifically but has no conventional antiarrhythmic properties, reduced mortality and VF. By means of order statistics the quantity 'risk of death' was used for evaluation of drug effects, considering incidence of death and VF as well as duration of VF. This quantity was reduced in correlation with the dose of alinidine (1-6 mg/kg i.v.) and in correlation with the reduction of heart rate. Mexiletine, an antiarrhythmic drug with membrane-depressant properties, also reduced the 'risk of death' dose dependently (1-10 mg/kg i.v.), but there was no correlation with a decrease in heart rate. It is suggested that alinidine reduced 'risk of death' by means of a reduced oxygen demand due to a decrease in heart rate.

Animals↗
PubMed1985

Indoramin-prolongation of repolarization time, a mechanism of bradycardia in man?

The effect of indoramin, a selective alpha 1-adrenoceptor antagonist, on ECG time intervals in normal man was studied. Significant prolongation of QTc was observed after indoramin 100 mg, with no change in QRS duration. In addition, the slope of the RR/QT relationship was changed by indoramin 100 mg. These results suggest that indoramin may have Class III antiarrhythmic activity. If such activity were to affect the SA node, it may explain at least in part the observed lack of reflex tachycardia after indoramin administration.

Adult↗
PubMed1985

Human pharmacokinetic and pharmacodynamic studies on Ro31-1118, a new beta-adrenoceptor antagonist.

The pharmacokinetic and pharmacodynamic effects of Ro31-1118 were examined in groups of healthy volunteers. In three subjects given 10 mg of [14C]-Ro31-1118 orally, peak levels of radioactivity (84 +/- 5 ng/ml) were 16 times those of the parent drug (approximately 5 ng/ml). Very little parent drug was recovered in the urine, although recovery of total radioactivity was nearly 80% in the urine by day 5. In five subjects studied after both oral and intravenous administration of 20 mg Ro31-1118 the average bioavailability was 57% (range 41-73%). Following intravenous infusion the apparent volume of distribution for the five subjects averaged 590 1 (range 510-700 1). The elimination half-life averaged 18 h (range 17-26 h). In eight subjects who received 40, 80, 160 and 320 mg of Ro31-1118 orally there was a linear relationship between dose and plasma concentration (r = 0.999) and between dose and AUC (r = 0.996). Ro31-1118 had no effect on resting heart rate whereas atenolol reduced resting heart rate up to 6 h after all doses. The maximum reduction of an exercise tachycardia after Ro31-1118 (320 mg) was 23.13 +/- 0.7% and compared with atenolol (100 mg) was 28.2 +/- 1.25%. At 24 h the percentage reduction after Ro31-1118 was 21.5 +/- 1.7%, while after atenolol the percentage inhibition had decreased to 11.1 +/- 1.6%. In three subjects Ro31-1118 (160 mg) orally had no effect on resting heart rate, forearm blood flow and systolic blood pressure, while atenolol (50 mg) reduced all three parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1985

Comparative effects of adimolol, labetalol and propranolol on heart rate and blood pressure in man.

The cardiovascular effects of adimolol, a new, potent, long acting beta-adrenoceptor blocking drug were investigated in three studies. In the first study blood pressure and heart rate were measured in five male volunteers before and at 2, 4, 6, 8, 24, 32, 48, 72 and 96 h after single oral doses of adimolol. All doses of adimolol reduced supine, standing and exercise heart rates in a dose dependent manner. The maximum effect ranged from 18% following 25 mg to 29% following 600 mg and all doses showed an effect at 96 h (range 3.5-17.2%). In the second study the effects of adimolol, 25 and 400 mg, labetalol, 200 and 800 mg, propranolol 40 mg and placebo were compared on supine and standing heart rate and blood pressure and on exercise heart rate before and at 2, 4, 6 and 8 h after single oral doses. The exercise heart rate was significantly reduced at all times following adimolol 25 and 400 mg, labetalol 800 mg and propranolol 40 mg. At 2 h all the drugs significantly reduced standing systolic blood pressure. In the third study, 4 h after single oral doses of adimolol 400 mg, labetalol 400 mg and propranolol 40 mg six subjects received serial 4 min infusions of phenylephrine. The blood pressure was measured after each infusion. Labetalol 400 mg significantly shifted the blood pressure dose-response curve to the right. There was no difference between propranolol 40 mg and adimolol 400 mg. These studies show that adimolol is a potent, long acting beta-adrenoceptor blocking drug without evidence of alpha-adrenoceptor blockade in man.

Adrenergic beta-Antagonists↗
PubMed1985

Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

ICI 118,551, 5 to 80 mg orally, did not significantly alter resting heart rate or blood pressure. In doses less than 40 mg the reduction in exercise tachycardia was under 10 beats/min. ICI 118,551, 10 to 40 mg, did not appear to reduce the maximum rise in systolic pressure with isoprenaline but did attenuate the changes in diastolic pressure, forearm blood flow and finger tremor. It also attenuated the isoprenaline-induced changes in serum glucose, insulin and potassium. On these observed changes, the effect of ICI 118,551 20 mg was similar to that of 40 mg and of propranolol 10 mg, but greater than that of atenolol 25 mg. An isoprenaline tachycardia was attenuated by all doses of ICI 118,551 studied. After atropine (0.04 mg/kg) ICI 118,551 20 mg still significantly reduced the effects of isoprenaline suggesting that functional beta 2-adrenoceptors may be present in the human heart. In doses less than 40 mg, ICI 118,551 appears to be a selective and competitive antagonist of beta 2-adrenoceptors in man.

Adrenergic beta-Antagonists↗
PubMed1985

Effects of azepexole and clonidine on baroreceptor mediated reflex bradycardia and physiological tremor in man.

The effects of oral administration of azepexole 10 mg, clonidine 300 micrograms and placebo on baroreceptor mediated reflex bradycardia and physiological tremor were investigated in six healthy volunteers. Both azepexole and clonidine reduced (P less than 0.05) systolic (120.5 +/-2.5 to 105.0 +/- 3.3 mm Hg; 115.8 +/- 2.6 to 104.7 +/- 2.8 mm Hg respectively) and diastolic (52.5 +/- 2.6 to 47.2 +/- 1.4 mmHg; 53.7 +/- 1.6 to 49.0 +/- 1.5 mmHg respectively) pressure when compared to placebo and to pre-treatment values. This reduction in pressure was not accompanied by a change in heart rate. Both azepexole and clonidine enhanced (P less than 0.05) baroreflex sensitivity to increases in systolic arterial pressure with phenylephrine. Clonidine facilitated (P less than 0.05) baroreflex sensitivity during the strain phase of the Valsalva manoeuvre, whereas azepexole reduced it (P less than 0.05). Neither clonidine nor azepexole altered finger tremor when compared to placebo or pre-treatment values. Azepexole produced (P less than 0.05) sedation compared to placebo but not when compared to pre-treatment values. Clonidine caused significant increases in sedation when compared to both placebo and to pre-treatment values. The differences between azepexole and clonidine may be due to the greater specificity of azepexole for the alpha 2-adrenoceptor than clonidine.

Adrenergic alpha-Agonists↗
PubMed1985

Comparison of the haemodynamic effects of bucindolol, propranolol and pindolol in healthy volunteers.

The effects of single oral doses of bucindolol (50, 100, 200 and 400 mg), pindolol (10 mg), propranolol (160 mg) and placebo on arterial pressure and heart rate in the supine and standing positions and exercise heart rate were compared in 12 healthy male volunteers. Supine heart rate was significantly greater after all four doses of bucindolol and pindolol in comparison to propranolol. Bucindolol had no significant effect on standing heart rate which was significantly reduced by pindolol and propranolol. Bucindolol, pindolol and propranolol significantly reduced an exercise tachycardia for at least 24 h after drug administration. Supine systolic pressure was not affected by any treatment but supine diastolic pressure was significantly reduced by bucindolol (200 and 400 mg) and by pindolol. All doses of bucindolol, propranolol and pindolol significantly reduced standing systolic blood pressure. There was a significant linear trend for reductions in standing systolic blood pressure and increasing doses of bucindolol. Standing diastolic blood pressure was significantly reduced by bucindolol 200 and 400 mg. Faintness and light headedness occurred in 6 of 12 subjects after 200 mg bucindolol and in 8 of 10 subjects after 400 bucindolol. After bucindolol, analysis of plasma samples demonstrated the presence of bucindolol, 5-hydroxy and 6-hydroxy bucindolol and indolyl-t-butylamine. These observations indicate that in man, bucindolol is a beta-adrenoceptor blocking drug with hypotensive activity and probably partial agonist activity. It is unlikely that the hypotensive effects result from blockade of beta-adrenoceptors or from the drug's partial agonist activity.

Adrenergic beta-Antagonists↗
PubMed1985

Effect of 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1 H-imidazo(4,5 h))isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimental cardiac arrhythmias in dogs.

The effects of intravenously administered 8-(3-diethylaminopropyl)-6,6-dimethyl-(2-phenyl-1H-imidazo (4,5H))-isoquinoline-7,9-(6H)-dione dihydrochloride (AR-LH31) on experimentally induced ventricular tachycardia were studied in dogs. Ventricular tachycardia was produced in 6 anaesthetised dogs by the intravenous injection of ouabain (66.7 +/- 4.9 mg/kg). AR-LH31 administered by increasing bolus injections every 5 min completely suppressed the ventricular tachycardia with a return to sinus rhythm in 1 out of 6 dogs, with a partial return of sinus beats in a second dog. There was no return to sinus rhythm in the 4 remaining dogs after doses ranging from 1.75 to 15.75 mg/kg. Observations were made in 9 conscious dogs 22-24 hours after ligation of the anterior descending branch of the left coronary artery when a ventricular tachycardia was present. The administration of AR-LH31 by bolus intravenous injection in 4 dogs did not abolish the arrhythmia in any dog but increased the number of sinus beats. In 3 out of 4 dogs after a cumulative dose of 7.75 mg/kg, 60% of ventricular beats were of sinus origin. The effects of larger doses could not be studied be cause of adverse effects. In 5 dogs the administration of AR-LH31 by constant intravenous infusion at 16 mg/kg/h restored sinus rhythm in all dogs after a mean dose of 9.9 +/- 0.9 mg/kg. These studies indicate that AR-LH31 has anti-arrhythmic activity in dogs and highlight the importance of the method of administration in determining the effects of a drug.

Animals↗