Comparison of Haemodynamic Responses to Cilnidipine and Nicardipine in an Experimental Model of Acute Congestive Heart Failure

Abstract

1. The haemodynamic effects of cilnidipine, a new calcium channel blocker, were examined in a canine model of acute congestive heart failure and were compared with those of nicardipine at equihypotensive doses. 2. The model was prepared by injections of saponin into coronary arteries of anaesthetized open-chest dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF) and left ventricular dP/dt markedly decreased, while left ventricular end-diastolic pressure (LVEDP), right atrial pressure and systemic vascular resistance (SVR) increased. Cilnidipine (0.3, 1.0 and 3.0 micrograms/kg per min), nicardipine (0.3, 1.0 and 3.0 micrograms/kg per min) or the respective vehicle was given i.v. after accomplishment of heart failure. 3. These drugs both produced a comparable reduction in aortic pressure and an increase in AoF associated with profound decreases in LVEDP, SVR and coronary vascular resistance. In contrast, administration of nicardipine was associated with significant increases in heart rate and cardiac contractility but that of cilnidipine was not. 4. These results indicate that cilnidipine as well as nicardipine can exert beneficial haemodynamic effects in a model of acute heart failure probably through lessening afterload and cilnidipine may moderate reflex-induced sympathetic stimulation.

A Two‐for‐One Bargain: Using Cilnidipine to Treat Hypertension and Its Comorbidities

“…10 They reported similar reductions in aortic pressure, left ventricular end-diastolic pressure, right atrial pressure, and coronary vascular resistance. 10 However, nicardipine increased heart rate and cardiac contractility, which was not seen with cilnidipine. Cilnidipine appeared to have moderate reflex-induced sympathetic stimulation.…”

“…However, nicardipine increased heart rate and cardiac contractility, which was not seen with cilnidipine. Cilnidipine appeared to have moderate reflex‐induced sympathetic stimulation . These results with cilnidipine may be related to a potent inhibitory action on the N‐type calcium channels by blunting the reflex‐induced sympathetic stimulation …”

“…Several studies have shown that cilnidipine blocks N‐type channels more potently than other CCBs by inhibiting the release of norepinephrine at the nerve endings and displays 10 times more potent coronary vasodilator action compared with other CCBs . Noguchi and colleagues studied open‐chest dogs using an acute heart failure model and compared nicardipine at equilhypotensive doses with cilnidipine . They reported similar reductions in aortic pressure, left ventricular end‐diastolic pressure, right atrial pressure, and coronary vascular resistance .…”

“…Noguchi and colleagues studied open‐chest dogs using an acute heart failure model and compared nicardipine at equilhypotensive doses with cilnidipine . They reported similar reductions in aortic pressure, left ventricular end‐diastolic pressure, right atrial pressure, and coronary vascular resistance . However, nicardipine increased heart rate and cardiac contractility, which was not seen with cilnidipine.…”

Why are calcium antagonists still being used in heart failure in the era of calcium sensitizers?

“…Cilnidipine led to vasodilatation without inducing reflex tachycardia, acting on the L and N channels (neuronal) 49 . Cilnidipine produced hemodynamic improvement without leading to sympathetic stimulation in experimental models, probably because of its N-channel blocking activity 50,51 . Bay y 5959 is another drug with antagonistic (it increases the inactivation ratio) and calcium agonistic effects (it increases the mean time for the opening of calcium channels).…”