Hemodynamic and antianginal effects during rest and exercise of intravenous isradipine, a new dihydropyridine calcium antagonist

In an open randomized study, hemodynamic and antianginal effects of nifedipine and the new dihydropyridine derivative isradipine were compared in patients with stable, angiographically confirmed coronary heart disease. Right heart hemodynamics, systemic arterial blood pressure, ECG, and drug plasma concentrations were measured before medication at rest and exercise, after infusions of increasing doses at rest, and again after treatment at rest and exercise. A linear relationship between serum concentrations and cumulated dosages was obtained for both drugs. At rest, both drugs significantly increased cardiac output and heart rate. The reduction of arterial blood pressure was significantly greater after isradipine (systolic from 148±3 to 104±3 mmHg; diastolic from 90±4 to 58±2 mmHg) than after nifedipine (systolic 149±6 to 125±4 mmHg; diastolic 92±4 to 76±3 mmHg). The minimal effective plasma level of isradipine regarding blood pressure reduction was estimated at 5 ng/ml (nifedipine: 10–25 ng/ml). During exercise both medications significantly reduced mean pulmonary artery pressure (isradipine: 40±3 to 20±1 mmHg, nifedipine: 37±4 to 22±1 mmHg), pulmonary artery wedge pressure (isradipine: 23±3 to 10±1 mmHg, nifedipine 24±3 to 14±1 mmHg), and diastolic arterial pressure (isradipine: 103±3 to 73±4 mmHg, nifedipine: 99±3 to 91±2 mmHg), whereas systolic pressure was reduced by only isradipine (189±4 to 147±5 mmHg). Neither medication significantly changed electrocardiographic ST depression during exercise. There was a high rate of painless ST depression (nifedipine 1/8, isradipine 4/8) during the drug dosing and increased ST depression during exercise. This phenomenon can be explained by either coronary steal or by ST depression of unknown origin after dihydropyridine treatment.