The Acute Hemodynamic Effects of Diazoxide in Man

Abstract

sor effect lasts about 5 hours (range = 2 to 24 hours). In animals,5 and in man6-8 diazoxide may cause salt and water retention that can be eliminated by the addition of a diuretic benzothiadiazine. Materials and MethodsAll patients studied were from the Moore Clinic of the Johns Hopkins Hospital, Baltimore. Observations were made on 14 Negro subjects who were divided into three groups. The first group was composed of five hypertensive patients with an average age of 48 years, and an average mean arterial blood pressure of 132 mm. Hg. There were three women and two men. The second group was composed of five normotensive subjects with an average age of 46 years and an average mean arterial pressure of 110 mm. Hg. There were two women and three men. The third group contained four hypertensive patients whose average age was 41 years and average mean arterial pressure 131 mm. Hg. The groups did not differ in average body surface area or hypertensive classification (except the normotensive subjects).9 None of the 14 patients had received hypotensive drugs for the preceding 2 weeks.On the day of the acute study, each patient was in a fasting state. No sedative was given. Measurements of right atrial pressure, systemic arterial pressure, cardiac output, and heart rate were made with the patient in the supine position. A small catheter was introduced through the basilic vein and advanced until its tip was lying free within the right atrium. A Cournand needle was placed in a brachial artery. Pressures were recorded from the right atrium and brachial artery with Statham strain gages. Mean pressures were obtained by electrical integration. Pressure recordings were made immediately before cardiac output determinations. The catheter in the right atrium was filled with indocyanine green dye connected through a three-way stopcock to a dye reservoir and injection system. The needle in the brachial artery was connected through a short, small-bore, polyethylene tubing to the euvette of a Gilford densitometer. Dye solutions were made up before the study and a small amount of blood was added so that the dye in the injectate would be bound to plasma. Approximately 2.8 mg. of dye were used for each injection.

Sympathetic and parasympathetic components of reflex cardiostimulation during vasodilator treatment of hypertension.

“…In our patients it caused a 24% reduction of mean arterial pressure in the face of a 25% increase in cardiac output, and this compares with other studies (Bhatia & Frohlich, 1973;Hamby, Jankowski, Pouget, Dunea & Gannt, 1968;Rubin, Zitowitz & Hausler, 1963;Wilson & Okun, 1963). The compensatory rise in cardiac output could not be prevented by propranolol.…”

Comparison of effects of tolmesoxide (RX71107), diazoxide, hydrallazine, prazosin, glyceryl trinitrate and sodium nitroprusside on forearm arteries and dorsal hand veins of man.

“…Diazoxide has a balanced action on arterial and venous beds and the acute circulatory effects would be expected to be somewhere between the two extremes. The reported effects resemble those of hydrallazine more than glyceryl trinitrate: both peripheral resistance and arterial pressure fall; right atrial pressure is unchanged, but heart rate and cardiac output rise (Wilson & Okun, 1963). The effects of long term administration of drugs may differ from those of acute administration.…”

“…Nevertheless, the clinical effects of the dilator drugs studied correlate well with their acute circulatory actions and hence with their pattern of activity in arteries and veins. Diazoxide and hydrallazine are effective in the treatment of hypertension and lower arterial pressure without reducing cardiac output (Wilson & Okun, 1963;Judson, Hollander & Wilkins, 1957); they do not cause postural hypotension. Hydrallazine frequently provokes angina when given intravenously to patients with ischaemic heart disease (Judson et al, 1956); this probably results from the disproportionately large increase in heart rate relative to the fall in arterial pressure which, in the absence of venodilatation to reduce ventricular volume, would be expected to cause an increase in left ventricular work and oxygen requirements.…”

Diazoxide disposition and effect on vascular resistance and compliance in dogs.

“…Ogilvie and Mikulic" observed that diazoxide reduced both pre-and postcapillary resistance of the gracilis muscle vascular bed. In hypertensive man, diazoxide reduced arterial pressure and increased cardiac output with an unaltered or increased right atrial pressure 8 and without and hypertensive patients, 10 ' u forearm venous tone or distensibility was unaltered after bolus doses of diazoxide. However, Collier et al 11 observed an equal dilator effect in forearm arterial vessels and hand veins previously constricted with noradrenaline, during infusion of diazoxide into the brachial arteries of normal volunteers.…”