Problem of measuring the positive inotropic property of a vasodilating drug: an illustration using felodipine.

Abstract

A study was undertaken to determine the presence or absence in patients of positive inotropic activity in a vasodilator drug that improves cardiac output by virtue of that vasodilatation. Felodipine is a dihydropyridine calcium antagonist that has a positive inotropic effect at low concentration in the dog in vivo. In nine patients undergoing coronary angiography in whom heart rate was kept constant by atrial pacing the solvent for the intravenous administration of the drug was infused followed by the active solution. Haemodynamic variables were measured with the Mills combined left ventricular cathetertip manometer and aortic electromagnetic blood velocity transducer. Reflex positive inotropic effects were blocked with the beta adrenergic blocking drug atenolol. An index of contractility was used to assess inotropic effects--the maximum rate of rise of left ventricular pressure measured by cathetertip micromanometry; this was an isovolumic event and therefore not sensitive to arterial pressure change, and it was unaffected by changes in left ventricular end diastolic pressure. In all patients peripheral vasodilatation was observed in the plasma felodipine concentration range of 2-40 nmol.litre-1. In eight patients this was accompanied by an 11-36% increase in maximum rate of rise of left ventricular pressure, indicating a small positive inotropic effect. Felodipine appears to show both agonist and antagonist properties in man as well as in the dog.