Effect of repeated plasma exchange on steady state kinetics of digoxin and digitoxin.

The effect of repeated plasma exchanges on the steady state kinetics of digoxin (3 patients) and digitoxin (4 patients) was investigated in 7 patients. Plasma exchange was performed 3 times a week for 4 weeks up to 12 exchanges using a hollow fiber membrane. In each exchange, 4000 ml plasma were filtered within 1 to 2 h and replaced by an albumin containing (20 g/l) physiological electrolyte solution. Digoxin and digitoxin concentrations in blood and filtered plasma were measured by radioimmunoassay. The effects due to the amount eliminated by plasma exchange were distinguished from the effects due to hypoalbuminemia. The eliminative effect was confined to the plasma compartment. It resulted in a marginal decrease in the elimination half-life from 1.6 to 1.59 days for digoxin and 4.3 to 4.2 days for digitoxin. Theoretically, it can be calculated that the hypoalbuminemia caused an increase in the volume of distribution from 451 to 497 l (digoxin) and 35 to 50 l (digitoxin) and a further decrease in the elimination half-life from 4.2 to 4.1 days in the case of digitoxin (not digoxin). If given within 2 h prior to plasma exchange, 13 to 50% of the digitoxin dose (not digoxin) was eliminated. Alteration of digoxin and digitoxin dosage during repeated plasma exchanges is not recommended, but drugs should be given after, not before plasma exchange.

Hypotensive action of calcium antagonists as related to plasma noradrenaline and reactivity to noradrenaline.

From animal experiments it has been suggested that calcium antagonists owe their antihypertensive potency to a diminished sensitivity of the resistance vessels to circulating noradrenaline. We studied the effects of two calcium antagonists, nifedipine and verapamil, on blood pressure, reactivity to exogenous noradrenaline and plasma noradrenaline concentration in 10 patients with essential hypertension. In a cross-over comparison the patients were treated with nifedipine and verapamil for four weeks each. Both calcium antagonists led to a similar drop in arterial pressure. Resting plasma noradrenaline did not change during either treatment whereas a slight increase (P less than 0.05) in stimulated noradrenaline levels was observed during nifedipine treatment. The hypotensive effect of nifedipine was associated with a marked reduction (P less than 0.01) in the pressor effect of noradrenaline whereas no change in pressor response could be found during verapamil treatment. The results obtained suggest that an impairment of the pressor response to noradrenaline is not a general prerequisite for the antihypertensive action of calcium antagonists.

Potassium chloride versus voltage clamp contractures in ventricular muscle.

In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.