Penbutolol (Hoe 893d) in primary hypertension. Blood pressure effects, tolerance and plasma concentrations.

Penbutolol (Hoe 893d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I-II. The dose (50-100mg) needed to achieve the therapeutic goal, i.e. supine diastolic BP less than 95 mm Hg, was titrated individually. On a daily dose of penbutolol 83 +/- 19 mg (mean +/- SD) blood pressure (BP, mean +/- SD) fell from 180 +/- 21/112 +/- 8 mmHg on placebo to 154 +/- 25/94 +/- 14 mmHg. 18 patients who reached the therapeutic goal (responders) continued in a double blind, cross-over study versus placebo, during which the supine BP fell on average 20/10 mmHg on the same dose of penbutolol, and 2/1 mmHg on placebo. Plasma concentrations (mean +/- SD) of free 0.10 +/- 0.07 microgram/ml) and total (2.02 +/- 1.39 microgram/ml) penbutolol did not differ between responders and nonresponders, and were not correlated with the fall in BP. Side effects were mild and mostly well tolerated. One patient developed dermatitis and another an elevation of liver enzymes.

Quantitative evaluation of postectopic beats in the normal and failing human heart using indices derived from catheter-tip manometer readings.

Postextrasystolic potentiation was studied by means of a catheter-tip manometer in patients with and without cardiomyopathy. The results imply that the enhancement of the left ventricular contraction is increased in patients with cardiomyopathy.

Haemodynamic effects of the antiarrhythmic quaternary ammonium compound QX-572 in man.

The haemodynamic effects of N, N-bis(phenyl-carbamoylmethyl) dimethylammonium chloride (QX-572) in man were studied. A controlled study was performed to rule out a possible influence of the catheterization procedure as such on the results. Ten patients with mild to moderate aortic regurgitation were studied: based on clinical data the patients were divided into 2 groups of 5. Randomly it was decided that one group should constitute a control group receiving saline while the second group received QX-572 , MG/KG BODY WEIGHT. In both groups the administration was performed as a slow intravenous infusion during 30 minutes. Heart rate, pressures in brachial artery and right atrium, cardiac output, stroke volume, and systemic vascular resistance were determined before, during, and up to 30 minutes after completion of placebo or QX-572. These variable remained stable in the control group while QX-572 produced an increase in heart rate most pronounced at the end of the infusion period. A transient decrease in systolic and mean brachial artery pressure during the infusion, and during the same period a decrease in right atrial pressure. Cardiac output and systemic vascular resistance were unchanged by QX-572 but they were not measured during the infusion when the changes in pressures were most pronounced. QX-572 was thought to act as a peripheral vasodilator during the infusion. Left ventricular contractility was studied by means of pressure curves obtained from a catheter tip manometer placed in the left ventricle. The first derivative of the isovolumic left ventricular pressure at the highest level (45mmHg) common to all patients was used (dp/dt-45). No significant difference could be observed when comparing mean changes of dp/dt-45 for the two groups. In the control group there was a slight but significant increase in dp/dt-45 during the time of observation. In the QX-572 group the results varied between individuals. Two of the patients differed from all other patients in the control and QX-572 groups showing a decrease in dp/dt-45 which, when most pronounced at the end of the infusion period, was -31 and -28 per cent of the preinfusion levels, respectively. This decrease probably reflects reduction of contractility. It was concluded that QX-572 in a dose of 8 mg/kg body weight did not have any major haemodynamic drawbacks.