To compare the negative inotropic effects of the four
dihydropyridine-
calcium-channel-blockers nifedipine (NIF),
isradipine (ISR),
nisoldipine (NIS) and
felodipine (FEL) in man, the drugs were infused within 30 min intravenously in an equihypotensive dosage (NIF 2 mg, ISR 0.5 mg, NIS 0.5 mg, FEL 0.6 mg; 10 patients in each group) in patients with
coronary heart disease. As a control, an additional 10 patients received isotonic
saline solution following an identical protocol. The afterload reduction was submaximal (reduction of peripheral resistance: NIF -23 +/- 9%, ISR -24 +/- 10%, NIS -28 +/- 6%, FEL -27 +/- 6%; no significant difference for group comparison) with a similar kinetic and a steady state of the afterload reduction after one-half of the infusion period to achieve a comparable sympathetic reflex activation. Preload parameters (PAP, LVEDP) were unchanged in all groups. A reflex
tachycardia occurred in all treatment groups after 15 min of
drug infusion. Due to its negative chronotropic properties, the reflex
tachycardia was significantly attenuated after
isradipine as compared to the other drugs (heart-rate changes: NIF +13 +/- 7%, p < 0.01; ISR +4 +/- 7%, not significant; NIS +20 +/- 10%, p < 0.01; FEL +17 +/- 12%, p < 0.01). Because of the baroreflex and sympathetic reflex activation the left-ventricular dp/dtmax increased after
isradipine (+14 +/- 10%, p < 0.01) and
nisoldipine (+16 +/- 13%, p < 0.01). The lack of a significant dp/dtmax increase in spite of a comparable afterload reduction after
felodipine (+5 +/- 8%, not significant) or
nifedipine (-3 +/- 6%, not significant) must be a consequence of the cardiodepressive properties of these drugs. Therefore, in an equihypotensive dosage, the strongest negative inotropic effects were observed after
nifedipine, lesser effects after
felodipine (p < 0.03), and the weakest cardiodepressive effects after
isradipine (p < 0.01) and
nisoldipine (p < 0.01). For clinical applications the lesser cardiodepressive properties of the new
dihydropyridine-derivatives should be advantageous in patients with already reduced left-ventricular performance or for use in combination with other negative inotropic drugs, e.g., betablockers.