Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure.

Abstract

SUMMARY Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.Dopamine is well established in the management of acute or acute on chronic heart failure. 2 The clinical value of dopamine, however, is often limited by alpha adrenoceptor mediated peripheral constriction,34 which increases the load faced by the left ventricle during ejection. Consequently myocardial oxygen demand increases and myocardial ischaemia may be induced in patients with coronary artery disease.5 Dopexamine (Fisons Pharmaceutical Division) is a recently synthesised compound which is structurally related to dopamine (Fig. 1). Like dopamine it can only be administered intravenously. In vitro and in vivo animal experiments show that the drug activates postjunctional dopamine receptors (equipotently with dopamine), has substantial beta2 adrenoceptor agonist activity, has no beta, adrenoceptor agonist activity, and, unlike dopamine, is inactive at Requests for reprints to Dr J R Dawson,

Comparison of the effects of dopamine, dobutamine, and dopexamine upon renal blood flow: a study in normal healthy volunteers.

“…Baroreceptor reflexes are reduced in patients with heart failure (Cohn & Franciosa, 1977) and thus dopexamine should produce less tachycardia in such patients (Brown et al, 1985b). Indeed, there was less tachycardia in patients treated with dopexamine for chronic heart failure (Dawson et al, 1985;Svenson et al,1986)than in our healthy volunteers.…”

Inhibition of Uptake1 by dopexamine hydrochloride in vitro)

“…An afterload-reducing agent and renal vasodilator with positive inotropic activity, dopexamine hydrochloride improves cardiac function in patients with heart failure (Dawson et al, 1985;Svensson et al, 1986) and suspected coronary artery disease (Jaski et al, 1986). Plasma levels typically obtained in man (0.02-0.61M; internal reports and Jaski et al, 1986) and in anaesthetized dogs (0.08-0.4tiM; Dr D Hall, personal communication) with therapeutic-dose infusions of dopexamine hydrochloride, would on the basis of these in vitro studies, be within the concentration range able to produce Uptake, block, and it is suggested that the inotropic response is partially mediated by Uptake, blockade and hence potentiation of endogenous noradrenaline.…”

Inodilation - The Way Ahead in the Early Therapy of Congestive Heart Failure?

“…On the other hand, in an abstract, Clowdus et al [1986] report that in early congestive heart failure (New York Heart Association Cate gories I and II), ibopamine was as effective as hydrochlorothiazide in a placebo-con trolled double-blind trial testing up to 10 months. Goldberg and Rajfer [1985], Dawson et al [1985], and Dei Cas et al [1983].…”