[Adrenergic beta receptor blockaders. Selectivity of beta blockaders and their self-stimulating effects].
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Biomedical subjects
Publications and source records attributed to T L Svendsen.
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The cardiovascular and adrenergic responses to cigarette smoking during acute selective and non-selective beta adrenoceptor blockade were studied in seven young healthy volunteers in a double blind cross-over fashion. Heart rate, arterial blood pressure, forearm blood flow and plasma levels of adrenaline and noradrenaline were determined before and during the terminal 5 min period of 15 min smoking test. During smoking, plasma concentrations of adrenaline increased markedly and evenly by approximately 0.3 ng/ml in all three experimental sessions. Plasma concentrations of noradrenaline remained unchanged. Propranolol, a non-selective beta blocker, caused a marked rise in diastolic and mean blood pressure and forearm vascular resistance during smoking. This response was not seen in the control series or after selective beta-1 blockage with atenolol. This difference is attributable to propranolol's blockade of adrenaline's vasodilating effect mediated by beta-2 receptors in the resistance vessels. Furthermore, atenolol attenuated the systolic blood pressure and tachycardiac responses induced by cigarette smoking by comparison with placebo. This study suggests that selective beta-1 blockers are preferable in the management of patients who are habitual smokers.
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A new multivariate stepwise linear regression analysis (Cox's model) with survival time as prognostic endpoint was utilized in 281 patients with acute myocardial infarction. From 18 prognostic factors occurring during the first 5 days in the Coronary Care Unit a new prognostic index was calculated for the chance of survival in the first 36 days after admission. The significant prognostic variables were heart failure, cardiogenic shock, atrioventricular block and age. The total group of patients was classified in 6 subgroups with different mean indices and prognosis. There were 2 large groups of patients with relative bad and good prognosis (with and without heart failure). Over half of the patients had no prognostic variables. There was a trend of overestimating the expected deaths. A definite cardiac cause of death was shown by 23 patients (82%). This prognostic index based on the 4 variables can for the individual patient predict the chance of survival, which can be the basis of an individualized duration of hospital stay.
Injection i.v. of labetalol, a new adrenergic alpha- and beta-blocking agent, decreased arterial blood pressure in 9 hypertensive subjects resting in the supine position, when standing and during supine exercise. Heart rate after labetalol was unchanged in the resting supine position, and it fell in the latter two conditions. Plasma noradrenaline concentration was higher after labetalol in all three experiments as compared to a control study. Plasma adrenaline after labetalol was increased only in the standing position, when the highest plasma noradrenaline concentrations were observed. Blood glucose concentration tended to increase after labetalol, but the difference was not statistically significant. The changes in plasma noradrenaline and blood glucose after labetalol mimic findings observed after alpha-adrenergic receptor blockade. The beta-adrenergic receptor blocking property of labetalol is responsible for the reduced heart rate and it is likely to contribute to the higher plasma noradrenaline concentration observed when standing and during supine exercise.
The effect of adrenergic beta receptor blockade on the elimination rate of ethanol was studied in seven healthy young men. The studies were performed before and after 14 days of propranolol 240 mg/day: the ethanol was given per-orally--0.8 mg/kg b.w. The blood concentration of ethanol, glucose, lactate and glycerol, and the plasma concentration of free fatty acids and triglycerides were followed in samples from the superior vena cava taken every 20 min for four hours. The splanchnic hepatic blood flow was estimated with a single i.v. injection of indocyanine green. The absorption rate, absorption fraction and elimination rate of ethanol were not changed by propranolol. The splanchnic hepatic blood flow was significantly reduced (mean 19 per cent) during beta receptor blockade. The ethanol-induced change in the concentration of glucose, lactate and free fatty acids was affected by propranolol, the time-concentration curves for glucose and lactate being significantly elevated and that for free fatty acids being significantly reduced. The time-concentration curves for glycerol and triglycerides did not differ in the two studies.
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The distensibility of the resistance vessels of skeletal muscle was evaluated in 23 patients with essential arterial hypertension (WSHO grade I--II), and in 14 normotensive control sugjects. Five of the hypertensive patients were well treated for over 2 years and 18 were untreated. The 133Xenon wash-out rate from the anterior tibial muscle during reactive hyperemia was recorded before and during an increase of the vascular transmural pressure, brought about by application of a subatmospheric pressure to the leg. At ambient pressure the 133Xenon wash-out rate did not differ between the normotensive and hypertensive subjects, reflecting equal muscle blood flows. However, when the transmural pressure was augmented the 133Xenon wash-out rate in the normotensive subjects increased about twice as much as in the hypertensive patients. This suggests a decreased distensibility of the resistance vessels in hypertensive patients as compared to normotensive subjects, and supports the concept that structural changes of these vessels take place in arterial hypertension. Since the vascular distensibility was equally reduced in the untreated and well treated hypertensive patients it is indicated that the structural changes in the resistance vessels of the leg muscles do not readily decline during antihypertensive treatment.
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Diphenylhydantoin (DPH) and tolbutamide serum levels were studied in ten volunteers before and after 4 days of disulfiram treatment. The mean DPH half life increased significantly from 11.0 +/- a.2 h to 19.0 +/- 3.3 h, and the mean DPH metabolic clearance rate decreased significantly from 51.2 +/- 17.2 ml/min to 33.9 +/- 12.0 ml/min during medication. No significant changes in the half life or metabolic clearance rate of tolbutamide was observed.
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