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

A number of long-term clinical trials involving over 40,000 patients have been performed to study the effectiveness of antihypertensive therapy in controlling high blood pressure and in reducing the morbidity and mortality associated with hypertension. Only diuretics and beta blockers have been studied in long-term trials to determine their efficacy in reducing cardiovascular morbidity and mortality. The Hypertension Detection and Follow-Up Program (HDFP), Medical Research Council (MRC) trial, European Working Party on Hypertension in the Elderly (EWPHE) trial, Australian Therapeutic Trial in Mild Hypertension, and the Veterans Administration Cooperative Study all showed a reduction in stroke rate. The EWPHE and HDFP trials were the only studies to show a statistically significant reduction in mortality from myocardial infarction. All of these were diuretic-based; in addition, the MRC trial also used a beta blocker as first-step therapy in 1 cohort. The International Primary Prospective Prevention Study in Hypertension and Heart Attack Primary Prevention in Hypertension (HAPPHY) trials compared beta-blocker and non-beta-blocker or diuretic-based therapies and found no significant difference between the treatment groups in the incidence of stroke or cardiac events. Neither study had a control group, so it was impossible to determine if there was any reduction in stroke or cardiac events. The Metoprolol Atherosclerosis Prevention in Hypertension trial, an extension of the HAPPHY trial, showed that smokers receiving the beta blocker metoprolol had a significantly lower cardiovascular mortality rate than those randomized to a diuretic drug. However, subgroup analysis of the HAPPHY data showed no differences in the effect of beta blockers and diuretics in smokers.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Review of the long-term controlled trials of usefulness of therapy for systemic hypertension. 256 89

Benzothiadiazine diuretic agents and beta-adrenergic receptor-blocking drugs are two of the main groups of drugs used to treat mild hypertension. Recently, questions have been raised about their relative efficacy in preventing morbidity and mortality from vascular disease in addition to their effect on lowering blood pressure. Attention has been focused on the unfavorable metabolic effects of diuretic drugs and the proven value of beta-adrenergic receptor blockade in secondary prevention after myocardial infarction. Four randomized controlled trials comparing drugs in these two classes have been published: the Medical Research Council trial, the International Prospective Primary Prevention Study in Hypertension, the Heart Attack Primary Prevention in Hypertension trial, and the Metoprolol Atherosclerosis Prevention in Hypertension study. These trials, especially that of the Medical Research Council, have raised some questions about the relative efficacy of these two classes of drugs in preventing stroke in smokers and nonsmokers. Overall, there is little evidence of a reduction in morbidity and mortality after myocardial infarction. The predicted advantage of beta-adrenergic receptor blockade over diuretic therapy has not been realized although there are sufficient hints of a differential benefit to encourage the performance of further trials.
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PMID:Diuretic agents and beta-blockers in the treatment of hypertension. 257 61

The haemodynamic effects of enflurane (1.7% and 3.4% expiratory concentrations) were investigated in sheep (n = 6) pretreated with an infusion of metoprolol (0.2 mg X kg-1 X h-1 for 5 days) and in control animals (n = 6). Chloralose was used as basal anaesthetic. A 90 s apnoea period was included in the experiment to evaluate further the possible side-effects of long-term metoprolol treatment in combination with enflurane anaesthesia. MAC 1.0 for enflurane in the sheep was found at 1.45% end-tidal concentration by separate measurements. Before enflurane administration, the only significant differences between the two groups of animals were a lower systemic vascular resistance and a higher stroke volume during metoprolol treatment. Enflurane abolished these discrepancies in a dose-dependent fashion and similar cardiovascular depression was observed in both groups of animals at 3.4% expiratory concentration of enflurane. Metoprolol did not significantly affect the hypertensive response to apnoea during chloralose anaesthesia alone. At enflurane 1.7% expiratory concentration the apnoea response was small and only the metoprolol-treated animals showed a significant increase in left ventricular end-diastolic pressure. We conclude that 5 days of pretreatment with metoprolol in the sheep model does not significantly impair cardiovascular performance during enflurane anaesthesia.
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PMID:Cardiovascular effects of enflurane and asphyxia during long-term beta 1-adrenoceptor blockade. 286 1

The antihypertensive efficacy of a new beta-receptor blocking agent, celiprolol, was compared with that of a well-established antihypertensive drug, metoprolol. Their systemic and forearm hemodynamic effects were investigated using echocardiography and two-dimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive patients completed a double-blind, cross-over, randomized study using celiprolol and metoprolol. Two six-week courses with celiprolol or metoprolol were preceded and followed by a two-week placebo period; the total duration of the study was 18 weeks. In spite of a comparable efficacy in reducing systolic and diastolic blood pressure (about 10% of the basal value), the two drugs showed quite different systemic and regional hemodynamic effects. Celiprolol induced a significant decrease in forearm vascular resistance (from 157 +/- 17 to 113 +/- 13 mm Hg/mL/s, P less than .01) and total peripheral resistance (from 1596 +/- 90 to 1398 +/- 91 dyne.s.cm-5, P less than .05) whereas cardiac output remained unchanged and forearm blood flow increased. Metoprolol reduced cardiac output (from 6.5 +/- 3 to 5.7 +/- 3 L/min, P less than .05), through a reduction in heart rate, since stroke volume was unchanged. Both drugs did not significantly modify cardiac performance, as evaluated by left ventricle fractional shortening and ejection fraction. Thus, the two drugs seem to reduce blood pressure through different hemodynamic mechanisms.
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PMID:Effects of celiprolol on systemic and forearm circulation in hypertensive patients: a double-blind cross-over study versus metoprolol. 288 95

The antihypertensive efficacy of a new beta-blocker, celiprolol, was compared with that of a well established antihypertensive drug, metoprolol. Systemic and forearm haemodynamic effects were investigated using echocardiography and two-dimensional pulsed Doppler flowmetry, respectively. Twenty hypertensive patients completed the double-blind crossover randomized study. Each 6-week active treatment period was both preceded and followed by 2 weeks of placebo treatment such that the total duration of the study was 18 weeks. Despite comparable efficacy in reducing systolic and diastolic blood pressures by approximately 10% of the basal value, the two drugs differed in their systemic and haemodynamic effects. Celiprolol significantly decreased forearm peripheral resistance and total peripheral resistance. Cardiac output remained unchanged and forearm blood flow was increased. Metoprolol reduced cardiac output through a reduction in heart rate, but stroke volume was unaltered. Neither drug significantly modified cardiac performance, as evaluated by left ventricular circumferential fibre shortening and left ventricular ejection fraction. Differences in the systemic and regional haemodynamic effects of the two drugs could account for the different blood pressure response seen in some patients. There was no observable change in left ventricular wall thickness or left ventricular mass. These results confirm previous reports which demonstrate that antihypertensive treatment with beta-blockers does not reduce left ventricular mass in patients with a left ventricle of normal size. It is generally accepted, however, that the ability of beta-blockers to reverse left ventricular hypertrophy is unrelated to the individual pharmacological characteristics of each agent.
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PMID:Long-term reduction of peripheral resistance with celiprolol and effects on left ventricular mass. 290 18

Cardiovascular, sympathoadrenal, and subjective responses to mental stress induced by a color-word conflict test (CWT) were studied in 30 healthy males before and after intravenous administration of either placebo, beta 1-blockade by metoprolol (0.15 mg/kg), or nonselective beta-blockade by propranolol (0.15 mg/kg). CWT responses were reproducible. Mean arterial pressure increased by 20%. A mainly heart rate-dependent 65% increase in cardiac output (thermodilution) was associated with 25% decreases of both systemic (SVR) and calf vascular (CVR) resistances. Arterial plasma epinephrine (Epi) was doubled, and norepinephrine (NE) increased by 50%. Self-evaluated stress score correlated positively with changes in cardiac output and inversely with changes in SVR during CWT. Both metoprolol and propranolol halved heart rate responses; whereas increases in mean arterial pressure, Epi, and NE were uninfluenced. Metoprolol reduced the increase in stroke volume, and propranolol abolished it. SVR and CVR responses were attenuated by metoprolol and abolished by propranolol. The results suggest that mental stress accelerates the heart through neurogenic mechanisms and that peripheral vasodilatation is achieved through the concerted actions of reduced vasoconstrictor activity and elevated circulating Epi.
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PMID:Cardiovascular and sympathoadrenal responses to mental stress: influence of beta-blockade. 320 6

While long term beta-adrenergic blockade, introduced in the convalescent stage of myocardial infarction, may reduce subsequent mortality, the value of early beta-blockade in the acute phase is less certain. Therefore, the influence of beta-blockade on left ventricular performance and eventual infarct size was assessed in 61 consecutive patients with acute myocardial infarction. Metoprolol (15 mg i.v. followed by 200 mg day-1 orally) or placebo was administered in a double-blind, randomised fashion with a median delay of 5.9 hours from onset of symptoms. After 15 days of double blind therapy all patients were started on open treatment with metoprolol. All patients underwent haemodynamic monitoring for 24 hours and serial radionuclide ventriculography and thallium 201 scintigraphy. In the first hour metoprolol produced a decrease in cardiac output (1.3 l min-1; P less than 0.001) due to a reduction in heart rate (15 min-1; P less than 0.001) and a decrease in left ventricular stroke work index (10.7 g m m-2; P less than 0.001) due to a reduction in mean arterial pressure (10 mmHg; P less than 0.001). There was then a gradual attenuation in these changes. While metoprolol produced an increase in pulmonary capillary wedge pressure and in both end-diastolic and end-systolic volumes (P less than 0.05), these changes were confined to patients with a baseline pulmonary capillary wedge pressure below the median of 13 mmHg mercury. There was no significant change in stroke volume or in ejection fraction in response to metoprolol. There was no significant difference between the groups in left ventricular performance, as assessed by radionuclide ventriculography, or in scintigraphic infarct size, either at the end of the 15 days double-blind treatment or after 3 months open treatment with metoprolol. Thus, early intervention with metoprolol in acute myocardial infarction appeared to reduce myocardial oxygen consumption with no adverse haemodynamic effect. However, metoprolol failed to preserve left ventricular function, or to reduce apparent infarct size. These data suggest that the modest reduction in mortality reported in the acute phase studies of beta-blockade in myocardial infarction, is unlikely to be due to infarct reduction. It is more likely to be due to a secondary prevention or to an antiarrhythmic effect.
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PMID:Beta-adrenergic blockade in acute myocardial infarction: a haemodynamic and radionuclide study. 331 55

Spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) were treated with a combination of a beta 1-blocker (Metoprolol) and a calcium antagonist (Felodipine) from 1 to 4 or from 4 to 6 months of age. Cross sections of plastic embedded basal cerebral arteries were measured with a digitizer. The ratio between media thickness and luminal radius (m/r ratio) could then be calculated for a standardized condition assuming a smooth, circular internal elastic membrane. The treatment caused a significant decrease of the m/r ratio in various basal cerebral arteries of young and adult SHR and SHRSP, i.e. the therapy may prevent as well as reverse hypertensive structural changes. Unilateral superior cervical ganglionectomy or preganglionic denervation did not affect the structure of basal cerebral arteries in young SHRSP or normotensive controls. A slight decrease of m/r ratio was indicated in the smallest pial arteries on the sympathectomized side, but the results did not allow any conclusion as to differences in effect between preganglionic denervation and ganglionectomy.
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PMID:Does sympathectomy or antihypertensive treatment affect the morphometry of basal cerebral arteries in spontaneously hypertensive rats? 346 52

In order to evaluate the use of Doppler echocardiography in the assessment of the haemodynamic effects of antihypertensive drugs, the acute haemodynamic response to felodipine and additional administration of metoprolol after 90 min was assessed in 10 hypertensive patients, by using both the Fick method and Doppler blood flow velocimetry in the ascending aorta. Intrabrachial artery pressure was significantly reduced by the treatment. Both the Fick and Doppler estimates of cardiac output (CO) rose significantly with felodipine and reached their highest values after 30 min, 45 +/- 8% (s.e.m.) and 58 +/- 7%, respectively. The felodipine-induced increase of heart rate (HR) persisted for 90 min, but the increase of stroke volume was only transient. Metoprolol brought CO and HR back to control levels. The felodipine- and metoprolol-induced changes of CO and stroke volume (SV) from control were on average not different between the observations with the Fick and the Doppler techniques throughout the study. As for the absolute values (control period), the Doppler measurement under-estimated SV (10 ml) and CO (1.1 l/min) in comparison with the Fick method, and the limits of agreement (mean difference +/- 2 s.d.) between both methods were 42 and -22 ml for stroke volume and 3.4 and -1.2 l/min for CO. In conclusion, despite the poor agreement in absolute results between the two methods, aortic Doppler velocimetry reflects the acute haemodynamic changes induced by felodipine and metoprolol in a group of hypertensive patients. The technique should facilitate the study of haemodynamic effects of drugs in man.
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PMID:The use of Doppler echocardiography to assess the acute haemodynamic response to felodipine and metoprolol in hypertensive patients. 361 65

The interaction of a new slow-calcium blocker (nisoldipine) and the beta-blocker metoprolol was evaluated in 16 patients with stable angina. Haemodynamic parameters were determined in a control rest and exercise period. Patients were then randomised equally to nisoldipine (4-8 micrograms/kg) or metoprolol (10 mg) and the haemodynamics of monotherapy assessed; finally the second drug was administered and the effects of combination determined. At rest nisoldipine reduced systemic blood pressure and vascular resistance (P less than 0.01); heart rate, cardiac and stroke volume indices increased (P less than 0.01) at an unchanged pulmonary artery occluded pressure. Metoprolol alone reduced heart rate (P less than 0.05) and increased the pulmonary artery occluded pressure (P less than 0.05). Combination therapy reduced systemic blood pressure and vascular resistance (P less than 0.01); cardiac index and pulmonary artery occluded pressure increased (P less than 0.01) at an unchanged heart rate. The effect of combination was influenced by the order of administration; an improvement in cardiac performance was particularly evident when nisoldipine was added to metoprolol. The interaction during dynamic exercise was similar to that at rest. Thus these data indicated the haemodynamic safety of concurrent nisoldipine/metoprolol therapy; the addition of nisoldipine to metoprolol appeared to offset in part the cardiodepressant properties of beta-blockade.
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PMID:A haemodynamic study of the effects of combined slow-calcium channel blockade (nisoldipine) and beta-blockade (metoprolol) in coronary heart disease. 379 80


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