The effects of nifedipine, a calcium antagonist, on platelet function.

Platelet function was studied before and 1 hour after ingestion of 20 mg nifedipine, a new calcium antagonist, in 20 patients with coronary heart disease. Platelet counts remained unchanged. Platelet adhesiveness, measured as retention in glass bead columns with Hellem's method for native blood, did not drop significantly eigher when 0.9 or 3.6 ml of blood was used. Platelet aggregation, which is dependent on extracellular calcium, was induced in citrated platelet-rich plasma. The mean maximal rate of primary aggregation, initiated with three different concentrations of adenosine diphosphate, was reduced by 20% to 26%. The rate of irreversible collagen-induced aggregation was on average 23% lower after nifedipine. The mean bleeding time was 36 seconds, or 12%, longer after ingestion of the drug. The moderate, but significant reduction of platelet aggregation and prolongation of the bleeding time by nifedipine may be mediated through inhibition of calcium transport across the platelet membrane.

Prolonged ventricular refractoriness and action potential duration after beta-adrenoreceptor blockade in the dog heart in situ.

We studied the effects of three different beta-adrenoreceptor-blocking drugs (atenolol, acebutolol, and propranolol) on the duration of monophasic action potentials and refractoriness of the right ventricular myocardium in closed-chest dogs. Pentobarbital anesthesia, which is known to increase the sympathetic tone, was used. Monophasic action potential recordings were obtained by the suction electrode technique, and refractoriness was measured by means of programmed electrical stimulation. A stepwise decrease in stimulation intervals from 350 to 300, 260, and 230 ms caused a progressive decrease in refractoriness as well as in the duration of the monophasic action potential. Intravenous injections of atenolol 0.5 mg/kg, acebutolol 2.0 mg/kg, and propranolol 0.5 mg/kg after pretreatment with atropine each increased the times for 50 and 90% repolarization of the monophasic action potential at each stimulation interval. The effective and the functional refractory periods paralleled the changes in the action potential duration in all experiments. We conclude that beta-adrenoreceptor blockade in the presence of adrenergic receptor stimulation prolongs ventricular refractoriness and action potential duration, and that the presence or absence of cardiac selectivity or slight intrinsic sympathomimetic activity plays no role in this process. These results suggest that if the antiarrhythmic action of beta-blocking drugs is due to prolongation of ventricular refractoriness, all types of these drugs may be expected to be equally effective as therapeutic agents.

Polymorphic acetylation of sulphadimidine in normal and uraemic man.

After oral administration of sulphadimidine (mean dose 3.33 g) to 21 volunteers it was possible to distinguish fast and slow acetylators by calculating the acetylated fraction (%acSDD) in a single serum sample obtained at any time between 1/2-24 h. There was a close correlation between %acSDD in serum and in urine collected from 0-8 h. Two groups of patients with chronic renal failure were studied. Four of the first 8 patients studied would have been designated as slow acetylators from their low %acSDD in 0-8 h urine, but as fast acetylators from their %acSDD in serum 6 h after drug administration. The next 18 patients were given a smaller dose of SDD (2 g) and they showed complete intra-individual correlation between %acSDD in 0-24 h urine and in a serum sample obtained at 24 h. The patients could be divided into 2 sub-groups on the basis of %acSDD in serum and urine, thus demonstrating the ability of this procedure to distinguish fast and slow acetylators, even in advanced chronic renal failure.

Maintenance therapy with a new retard tablet preparation of procainamide.

The procainamide plasma concentration was followed during maintenance therapy with a new procainamide retard tablet preparation in 23 hospitalized patients suffering from acute or chronic coronary heart disease with complicating ventricular arrhythmias. After initial individually adjusted treatment with Pronestyl every third hour, either orally or intramuscularly, for at least eight dose intervals, the retard tablets were given at 6 hour intervals for 2 to 12 days, or more. In 19 patients with no major fluctuations in their circulatory or renal state, adequate and relatively stable plasma procainamide concentration was obtained upon a constant dose of the retard preparation. On an average, the difference from minimum to maximum concentration was 55 per cent within the 6 hour dose intervals. In four patients with unstable circulation and/or renal function, procainamide therapy had to be disrupted in two because of severe side effects and toxic concentrations, and the dose was adjusted in the remaining two. It is concluded that the formulation of procainamide tablet preparations has simplified procainamide therapy within and outside hospital and improved our possibilities to perform short-and long-term studies on the risk/ benefit ratio of procainamide treatment in patients with severe ventricular arrhythmias.

Verapamil in the treatment of atrial tachycardia with block.

Atrial tachycardia (A-T) with block is easily converted as a rule to sinus rhythm by DC shock, but the recurrence rate is high. So far drug treatment of this arrhythmia has been unsatisfactory. There is no drug of choice in the treatment of A-T with block. We report on the effect of verapamil on this arrhythmia in 14 patients. Ten of them reverted to sinus rhythm, but A-T with block later recurred in 4. The best effect was found in patients with no or only minimal heart enlargement and in patients with short duration of the arrhythmia. The effect of verapamil on A-T with block may support the concept of this arrhythmia being due to atrioventricular (A-V) nodal reentry, as the main effect of verapamil is a prolongation of the effective refractory period of the A-V node.

Effects of N-acetylprocainamide as compared with procainamide in isolated rat atria.

The actions of procainamide and its major metabolite N-acetylprocainamide were tested and compared on isolated rat atria. While procainamide exerted a negative chronotropic and iontropic effect, N-acetylprocainamide had the opposite effect. It is suggested that a N-acetylprocainamide-induced increase in myocardial work can counteract the negative inotropic action of procainamide and thus to some extent explain the variable results with the latter compound on myocardial performance reported from in vivo experiments. Procainamide increased the refractory period and reduced the excitability of isolated rat atria. N-acetylprocainamide, on the other hand, caused negligible effects on these parameters.