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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of propafenone on the pharmacokinetics and pharmacodynamics of propranolol were evaluated in 12 healthy male subjects. Both propafenone and propranolol were each administered alone for one week followed by concomitant administration for an additional week. Blood samples, obtained at steady-state, were analyzed for propafenone and its two metabolites as well as for propranolol and 4-hydroxypropranolol. Left ventricular function, exercise performance and electrocardiographic intervals were assessed. Coadministration of propranolol did not produce any significant change in propafenone kinetics including peak plasma concentration (Cmax), time to peak plasma concentration (Tmax), elimination rate constant (t1/2), mean steady-state plasma concentration (Css), or area under the concentration vs time curves. However, concomitant propafenone administration significantly increased Cmax (83%), Tmax (55%), t1/2 (30%), and Css (213%) which were accompanied by significant decreases in plasma levels of 4-hydroxy-propranolol. Propafenone and propranolol significantly reduced supine systolic and diastolic blood pressure by 2.5 to 15.4%. The combination did not reduce diastolic blood pressure further (64.0 +/- 2.8 to 59.7 +/- 1.7 mmHg) nor did it produce a supplemental reduction in heart rate (12% reduction with propranolol, 10% reduction with concomitant administration). Propranolol, but not propafenone, significantly decreased end-diastolic volume index (13%), stroke volume index (15%), and velocity of circumferential fiber shortening (19%). The combination did not cause any further changes in echocardiographic measurements. Electrocardiographic intervals were not altered by either drug use alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interaction between propranolol and propafenone in healthy volunteers. 275 20

The effects of nifedipine and propranolol on cardiac function both at rest and at peak exercise were compared in 22 hypertensive patients whose diastolic blood pressures remained in excess of 95 mm Hg despite diuretic therapy. In this double-blind, placebo-controlled study, left ventricular systolic and diastolic function at rest and at peak exercise during bicycle ergometry was assessed by first-pass radionuclide angiography using the Baird Scinticor before and after treatment with either nifedipine or propranolol. Both agents effectively reduced blood pressure in the supine and upright positions and at peak exercise. Nifedipine was associated with a significant increase in cardiac output and stroke volume at rest and at peak exercise, while propranolol decreased cardiac output at rest and at peak exercise. Systemic vascular resistance decreased with nifedipine treatment at rest and at peak exercise, but increased significantly with propranolol. Nifedipine increased ejection fraction in patients at rest and also increased maximal oxygen consumption at peak exercise, while propranolol decreased maximal oxygen consumption at peak exercise. At rest and at peak exercise, nifedipine increased peak filling rate, but time to peak filling rate was not affected by either drug. The fraction of total diastolic filling at the midpoint of diastole was significantly increased by nifedipine therapy at rest but was not affected by propranolol therapy. Nifedipine significantly decreased atrial filling volume while propranolol had no effect. Propranolol therapy did not result in any improvement in left ventricular function. In contrast, nifedipine improved left ventricular systolic and diastolic function at rest and peak exercise. Future selection of an antihypertensive agent should include consideration of the impact of therapy on left ventricular function.
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PMID:Nifedipine, but not propranolol, improves left ventricular systolic and diastolic function in patients with hypertension. 278 71

A model of patent ductus arteriosus in premature lambs was created to study the relative importance of beta-adrenoreceptor stimulation and increased myocardial contractility. In 39 fetal lambs (133 +/- 2, +/- SD days gestation, term 145 days), the ductus arteriosus was infiltrated with formalin, and a snare was placed around it to regulate its patency. One day later, the lambs were delivered, given sheep surfactant, paralyzed, and mechanically ventilated. Microsphere measurements of left ventricular output were made between 4 and 6 h after delivery. When the ductus was opened, there was no change in heart rate, but there were significant increases in left ventricular output, stroke volume, left ventricular end-diastolic pressure, and peak dP/dt. The increase in peak dP/dt due to opening the ductus was greater than that due to an increase in left ventricular end-diastolic pressure alone and was accompanied by an increase in norepinephrine secretion from the left ventricle. Propranolol (1 mg/kg) was used to evaluate the effect of beta-adrenergic tone on left ventricular output and contractility. The left atrium was paced in both control and propranolol-treated lambs. When the ductus was closed, propranolol significantly decreased stroke volume and peak dP/dt without changing left ventricular end-diastolic pressure or systemic vascular resistance. During a saline volume load (50 ml/kg over a 3-min period), propranolol-treated lambs had a reduced stroke volume and peak dP/dt despite similar values of left ventricular end-diastolic pressure and resistance as those of control lambs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of beta-adrenoreceptor stimulation and contractile state in the preterm lamb's response to altered ductus arteriosus patency. 283 17

Cardiac hemodynamics and myocardial contractility were examined in patients with acute myocardial infarction during urgent aorto-coronary shunting with and without beta-adrenergic blockers. The beta-blockers were shown to have a protective effect, as reflected in a smaller myocardial strain owing to a decrease in heart rate, stroke and cardiac outputs, and pulmonary arterial blood pressure. Propranolol proved the most effective agent, whereas visken produced the smallest effect.
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PMID:[Contractile function of the myocardium and central hemodynamics in acute myocardial infarct patients after a single intravenous injection of adrenergic beta receptor blockaders]. 287 2

We studied the cardiovascular profile of the new cardioselective beta-adrenoceptor antagonist bisoprolol in the conscious pig and compared this profile with that of propranolol. Acute i.v. administration of bisoprolol (16-1024 micrograms.kg-1) did not affect mean arterial blood pressure but caused dose-related decreases in cardiac output (from 8 to 17%; p less than 0.05) due to a negative chronotropic action (heart rate reduction ranging from 9 to 21%; p less than 0.05) as stroke volume was unaffected. Max LVdP/dt decreased (ranging from 18 to 27%; p less than 0.05) while left ventricular end-diastolic blood pressure (from 8.6 +/- 0.6 to 15 +/- 0.2 mmHg; p less than 0.05) and systemic vascular resistance (from 8 to 18%; p less than 0.05) increased. Propranolol in a dose-range from 25-300 micrograms.kg-1 produced strikingly similar changes. Bisoprolol was more effective in antagonizing the isoproterenol-induced responses of max LVdP/dt than those on either heart rate or diastolic arterial blood pressure, whereas propranolol caused equi-effective inhibitions of the responses of heart rate and max LVdP/dt. However, with propranolol also the inhibition of the diastolic arterial blood pressure was less marked than for the other parameters. Propranolol proved to be the more potent beta-adrenoceptor antagonist, as the isoproterenol dose ratios of all 3 parameters during beta-adrenoceptors blockade with propranolol exceeded those obtained with bisoprolol.
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PMID:Systemic haemodynamic and beta-adrenoceptor antagonistic effects of bisoprolol in conscious pigs: a comparison with propranolol. 289 11

Migraine is associated with increased platelet activity and an incidence of cerebrovascular ischemic events. Because cerebrovascular events might result from platelet aggregation, enhancing platelet activity further in the treatment of migraine is not desirable. beta-Adrenoceptor blockers effective in migraine prophylaxis include propranolol (nonselective) and metoprolol (beta 1-selective), but it is uncertain how beta-receptor subtype selectivity might influence platelet behavior in migraine. In 29 patients, comparable clinical responses were obtained with therapeutic doses during 1 month of treatment with propranolol, metoprolol, and the beta 2-selective Li 32-468. Propranolol increased and metoprolol decreased platelet aggregation and ATP release, and the effect of Li 32-468 could be related to that of propranolol. These actions can be largely explained in terms of what is known of platelet beta-receptors and therefore can be generalized to other effective beta-blockers. Since altered platelet activity does not account for the efficacy of these agents in migraine, the actions of beta-blockers on platelets should be considered as side effects. Those beta-blockers inhibiting platelet activity should be preferred in migraine treatment, assuming equal efficacy, which implies the use of beta 1-selective blockers.
Stroke 1988 Jun
PMID:Platelet activity and selective beta-blockade in migraine prophylaxis. 289 33

Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.
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PMID:Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations. 291 May 41

Decreased maximal O2 uptake (VO2max) and stimulation of the sympathetic nervous system have been previously shown to occur at high altitude. We hypothesized that tachycardia mediated by beta-adrenergic stimulation acted to defend VO2max at high altitude. Propranolol treatment beginning before high-altitude (4,300 m) ascent reduced heart rate during maximal and submaximal exercise in six healthy men treated with propranolol (80 mg three times daily) compared with five healthy subjects receiving placebo (lactose). Compared with sea-level values, the VO2max fell on day 2 at high altitude, but the magnitude of fall was similar in the placebo and propranolol treatment groups (26 +/- 6 vs. 32 +/- 5%, P = NS) and VO2max remained similar at high altitude in both groups once treatment was discontinued. During 30 min of submaximal (80% of VO2max) exercise, propranolol-treated subjects maintained O2 uptake levels that were as large as those in placebo subjects. The maintenance of maximal or submaximal levels of O2 uptake in propranolol-treated subjects at 4,300 m could not be attributed to increased minute ventilation, arterial O2 saturation, or hemoglobin concentration. Rather, it appeared that propranolol-treated subjects maintained O2 uptake by transporting a greater proportion of the O2 uptake with each heartbeat. Thus, contrary to our hypothesis, beta-adrenergic blockade did not impair maximal or submaximal O2 uptake at high altitude due perhaps to compensatory mechanisms acting to maintain stroke volume and cardiac output.
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PMID:Propranolol does not impair exercise oxygen uptake in normal men at high altitude. 302 76

Tobacco smoking is a powerful risk predictor for coronary disease. In the recent Medical Research Council (MRC) Hypertension Trial, which this article discusses, it also proved to be an important predictor of stroke. The MRC trial had two active treatment groups, one of which received bendrofluazide and the other propranolol. The main positive result of the trial was a 45% reduction in stroke events in the actively treated groups. Propranolol appeared to be much less effective than bendrofluazide in the prevention of stroke in smokers, although both active drugs were equally effective in nonsmokers. Possible explanations for this lack of efficacy in smokers are discussed. Coronary events were not reduced by treatment, although there was a trend toward their reduction in nonsmoking men treated with propranolol. The lack of effect of propranolol in reducing coronary morbidity and mortality rates was a surprise in view of the positive results from trials with both short-term and long-term treatment with beta-adrenergic blockade after myocardial infarction.
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PMID:The Medical Research Council Hypertension Trial: the smoking patient. 333 95

1. To clarify whether the bradycardic agent UL-FS 49 exhibits a positive inotropic effect even in the absence of improvement in regional myocardial function of an underperfused myocardial area, this study was undertaken in dogs with unimpaired coronary flow. 2. We also investigated the haemodynamic and functional effects of the negative chronotropic and inotropic beta-adrenoceptor blocker propranolol. 3. UL-FS 49 did not depress total or regional myocardial performance. Moreover, an increase in positive left ventricular dp/dt max at rest suggests a positive inotropic effect of UL-FS 49. 4. Propranolol, in contrast to UL-FS 49, led to a marked reduction in positive dp/dt max, stroke volume and systolic wall thickening at rest and during exercise. Additionally, propranolol decreased the exercise values of cardiac output, left ventricular work and left ventricular power to a far greater extent than UL-FS 49. 5. In contrast to propranolol, the selective bradycardic agent UL-FS 49 did not decrease total or regional ventricular performance and caused less reduction in cardiodynamic parameters during exercise. 6. These results suggest that patients with moderate coronary insufficiency or patients with coronary vessel disease and mild left ventricular failure may attain a higher exercise limit under selective bradycardia with UL-FS 49 in comparison to that possible with a beta-adrenoceptor antagonist, such as propranolol.
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PMID:Comparison of the haemodynamic effects of the selective bradycardic agent UL-FS 49, with those of propranolol during treadmill exercise in dogs. 340 44


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