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

The circulatory consequences of concurrent slow-calcium channel (nicardipine) and cardioselective beta blockade (metoprolol) were evaluated in 20 patients with angiographically proven coronary artery disease. The rest and exercise haemodynamic impact of intravenous nicardipine (10 mg) or metoprolol (10 mg) alone was determined by randomly allocating 10 patients to each drug; finally all patients were assessed on combination therapy. The plasma levels of nicardipine (17 +/- 3 to 53 +/- 6 ng ml-1) and metoprolol (36 +/- 5 to 97 +/- 16 ng ml-1) achieved at the time of each study were in the established therapeutic range. At rest nicardipine reduced systemic mean arterial pressure and systemic vascular resistance index; cardiac and stroke volume indices increased without change in pulmonary artery occluded pressure. Metoprolol alone reduced systemic blood pressure, heart rate and cardiac index, and increased systemic vascular resistance index. Combination therapy reduced systemic arterial blood pressure and heart rate with relatively modest effects on cardiac index, systemic vascular resistance index and pulmonary artery occluded pressure. During dynamic exercise nicardipine reduced systemic mean and diastolic arterial pressure and stroke work index without change in other haemodynamic variables. Metoprolol reduced exercise systemic arterial pressures, heart rate and cardiac index, and increased systemic vascular resistance index and pulmonary artery occluded pressure. Combination therapy produced changes similar to those at rest; at peak nicardipine pharmacodynamic activity, the cardiac depressant actions of metoprolol were largely offset by the induced reduction in left ventricular afterload.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Haemodynamic analysis of the effects of nicardipine and metoprolol alone and in combination in coronary artery disease. 407 2

The long-term effects of metoprolol monotherapy, 100 mg b.i.d., for 16-18 months, were investigated in 8 previously untreated essentially hypertensive patients (resting blood pressure greater than 155/95 mmHg) and echocardiographic evidence of left ventricular hypertrophy (LVH) (left ventricular mass by Penn Cube formula greater than 215 g). Echocardiographic studies, according to the American Society of Echocardiography recording techniques and measurements criteria, were performed before starting treatment and at the end of follow-up. Metoprolol induced a decrease in systolic and diastolic blood pressure and heart rate, accompanied by a reduction of interventricular septum and posterior wall thickness (from 1.21 cm to 1.10 cm, and from 1.15 cm to 1.06 cm, respectively), left ventricular mass index and mean wall stress. All these changes were significant (p less than 0.01). Cardiac index decreased from 3017 ml/m2 to 2632 ml/m2 (p less than 0.01), mostly because of the reduction in the heart rate. In fact, stroke index, ejection fraction and fractional shortening all slightly increased during treatment in respect to pre-treatment values. Plasma renin activity fell from 1.45 ng/ml/h to 0.81 ng/ml/h (p less than 0.01), whereas both plasma noradrenaline and adrenaline concentration at rest did not change. Results indicate that in essentially hypertensive patients who have already developed LVH as a consequence of the hypertension, a long-term metoprolol therapy can successfully induce a reversal of LVH together with an effective blood pressure control, without noticeable adverse effects of changes in cardiac performance.
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PMID:Left ventricular hypertrophy regression in hypertensive patients treated with metoprolol. 623 55

1. The influence of sodium chloride (NaCl)-enrichment of the diet (6% of the dry weight) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of the beta 1-adrenoceptor blocking drug, metoprolol, was studied in stroke-prone spontaneously hypertensive rats. 2. Increased dietary sodium chloride intake produced a marked rise in blood pressure and induced left ventricular and renal hypertrophy. By contrast, the salt alternative did not increase blood pressure and caused remarkably less cardiac and renal hypertrophy than did sodium chloride. 3. Metoprolol treatment at a daily dose of 250 mg kg-1 lowered blood pressure and decreased left ventricular hypertrophy index during the control diet. Sodium chloride-enrichment blocked the antihypertensive effect of metoprolol, while a partial protective effect on left ventricular and renal hypertrophy persisted. In the presence of the salt alternative-enrichment both at the level of 6% and 10.5% (corresponding to a NaCl level of 6%), metoprolol was fully able to exert its beneficial cardiovascular and renal effects. 4. Both salt supplementations, irrespective of metoprolol treatment, induced a 3 to 4 fold increase in the urinary excretion of calcium. There was a linear correlation between the urinary excretions of sodium and calcium. The urinary excretion of magnesium rose by 90% and that of potassium by 110% in the salt alternative group. 6. Our findings suggest that replacement of common salt by a potassium-, and magnesium-enriched salt alternative in the diet produces beneficial cardiovascular effects and improves the antihypertensive efficacy of metoprolol in stroke-prone spontaneously hypertensive rats. Increased intake of potassium and/or magnesium and L-lysine from the salt alternative is involved in the beneficial effects of the salt alternative. The NaCl-induced myocardial and renal hypertrophies appear to be partially mediated by Beta-adrenoceptor activation.
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PMID:Improvement of cardiovascular effects of metoprolol by replacement of common salt with a potassium- and magnesium-enriched salt alternative. 807 82

Tremor has been rarely described as a manifestation of stroke. A 21-year-old left-handed man developed severe action tremor of his distal left upper extremity and hand following a right parieto-occipital intracerebral hemorrhage. Strength of the left upper extremity improved gradually during a 3-month period but a severe action tremor developed. The patient was treated with the cardioselective beta-blocking agent, metoprolol, initially for elevated blood pressure and tachycardia at 25 mg twice daily for approximately 2 months. Metoprolol was then increased at weekly intervals by 25mg twice daily to a total of 100mg twice daily. Tremor intensity decreased clinically and graphically as monitored by a trace test by having the patient attempt to trace a horizontal and vertical axis and scoring the errors. The scores declined weekly from the first week (4,347), second week (3,786), third week (1,088), to the fourth week (484). No adverse cognitive or cardiopulmonary effects were noted. Action tremor should be considered as one of the movement disorders caused by hemorrhagic cerebral infarction. This case responded well to treatment with metoprolol.
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PMID:Metoprolol for action tremor following intracerebral hemorrhage. 808 22

Nine healthy males participated in a double-blind, placebo-controlled, randomized, crossover study to determine the effects of verapamil and metoprolol administered alone and concurrently on blood flow through the hepatic artery and portal and hepatic veins and to detect a possible drug interaction between the two agents. Single oral doses of placebo/placebo, metoprolol (50 mg)/placebo, verapamil (80 mg)/placebo, or verapamil/metoprolol were separated by at least 14 days. Liver blood flow through individual hepatic vessels was measured up to 8 hours after dosage administration using a duplex Doppler ultrasound technique. Cardiac output, heart rate, blood pressure, stroke volume, and total peripheral resistance were measured for 3 hours after drug doses were given. In 5 subjects, pharmacokinetic parameters for total drug as well as S- and R-enantiomers were also measured. Verapamil given alone caused a rapid and intense increase in liver blood flow (hepatic artery = 50%, portal vein = 42%, hepatic vein = 55%) 0.75 to 1 hour after administration because of a decrease in total peripheral resistance and an increase in heart rate, stroke volume, and cardiac output. Metoprolol given alone caused a slow but prolonged decrease in liver blood flow (maximum decrease: hepatic artery = -54%, portal vein = -21%, hepatic vein = -27%) 4 hours after administration because of a decrease in heart rate and cardiac output. When the two agents were given together, a composite of the changes noted after separate administration was noted: a brief peak increase in liver blood flow at 0.33 to 1 hour followed by a slow, prolonged decrease that reached its maximum decline 4 to 5 hours postdose. During the combined phase, metoprolol and its enantiomers had an increased AUC and Cmax, while verapamil and its enantiomers had an increased AUC and t1/2. These pharmacokinetic changes were consistent with the magnitude and time course of liver blood flow changes through the hepatic artery and portal or hepatic veins.
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PMID:Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition. 1080 7

We sought to examine the importance of the cardiac component of the carotid baroreflex (CBR) in control of blood pressure during isometric exercise. Nine subjects performed 4 min of ischaemic isometric calf exercise at 20% of maximum voluntary contraction. Trials were repeated with beta1-adrenergic blockade (metoprolol, 0.15 +/- 0.003 mg kg(-1)) or parasympathetic blockade (glycopyrrolate, 13.6 +/- 1.5 microg kg(-1)). CBR function was determined using rapid pulses of neck pressure and neck suction from +40 to -80 mmHg, while heart rate (HR), mean arterial pressure (MAP) and changes in stroke volume (SV, Modelflow method) were measured. Metoprolol decreased and glycopyrrolate increased HR and cardiac output both at rest and during exercise (P < 0.05), while resting and exercising blood pressure were unchanged. Glycopyrrolate reduced the maximal gain (G(max)) ofthe CBR-HR function curve (-0.58 +/- 0.10 to -0.06 +/- 0.01 beats min(-1) mmHg(-1), P < 0.05), but had no effect on the G(max) of the CBR-MAP function curve. During isometric exercise the CBR-HR curve was shifted upward and rightward in the metoprolol and no drug conditions, while the control of HR was significantly attenuated with glycopyrrolate (P < 0.05). Regardless of drug administration isometric exercise produced an upward and rightward resetting of the CBR control of MAP with no change in G(max). Thus, despite marked reductions in CBR control of HR following parasympathetic blockade, CBR control of blood pressure was well maintained. These data suggest that alterations in vasomotor tone are the primary mechanism by which the CBR modulates blood pressure during low intensity isometric exercise.
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PMID:Cardiac and vasomotor components of the carotid baroreflex control of arterial blood pressure during isometric exercise in humans. 1651 74

To investigate the association between hyperinsulinemia and cardiac hypertrophy, we treated rats with insulin for 7 wk and assessed effects on myocardial growth, vascularization, and fibrosis in relation to the expression of angiotensin II receptors (AT-R). We also characterized insulin signaling pathways believed to promote myocyte growth and interact with proliferative responses mediated by G protein-coupled receptors, and we assessed myocardial insulin receptor substrate-1 (IRS-1) and p110 alpha catalytic and p85 regulatory subunits of phospatidylinositol 3 kinase (PI3K), Akt, MEK, ERK1/2, and S6 kinase-1 (S6K1). Left ventricular (LV) geometry and performance were evaluated echocardiographically. Insulin decreased AT1a-R mRNA expression but increased protein levels and increased AT2-R mRNA and protein levels and phosphorylation of IRS-1 (Ser374/Tyr989), MEK1/2 (Ser218/Ser222), ERK1/2 (Thr202/Tyr204), S6K1 (Thr421/Ser424/Thr389), Akt (Thr308/Thr308), and PI3K p110 alpha but not of p85 (Tyr508). Insulin increased LV mass and relative wall thickness and reduced stroke volume and cardiac output. Histochemical examination demonstrated myocyte hypertrophy and increases in interstitial fibrosis. Metoprolol plus insulin prevented the increase in relative wall thickness, decreased fibrosis, increased LV mass, and improved function seen with insulin alone. Thus our data demonstrate that chronic hyperinsulinemia decreases AT1a-to-AT2 ratio and increases MEK-ERK1/2 and S6K1 pathway activity related to hypertrophy. These changes might be crucial for increased cardiovascular growth and fibrosis and signs of impaired LV function.
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PMID:Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways. 1656 9

Lowering elevated blood pressure (BP) with drug therapy reduces the risk for catastrophic fatal and nonfatal cardiovascular events such as stroke and myocardial infarction. Given the heterogeneity of hypertension as a disease, the marked variability in an individual patient's BP response, and low response rates with monotherapy, expert groups such as the Joint National Committee (JNC) emphasize the value of combination antihypertensive regimens, noting that combinations, usually of different classes, have additive antihypertensive effects. Metoprolol succinate extended-release tablet is a beta-1 (cardio-selective) adrenoceptor-blocking agent formulated to provide controlled and predictable release of metoprolol. Hydrochlorothiazide (HCT) is a well-established diuretic and antihypertensive agent, which promotes natruresis by acting on the distal renal tubule. The pharmacokinetics, efficacy, and safety/tolerability of the antihypertensive combination tablet, metoprolol extended release hydrochlorothiazide, essentially reflect the well-described independent characteristics of each of the component agents. Not only is the combination product more effective than monotherapy with the individual components but the combination product allows a low-dose multidrug regimen as an alternative to high-dose monotherapy, thereby, minimizing the likelihood of dose-related side-effects.
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PMID:Metoprolol succinate extended release/hydrochlorothiazide combination tablets. 1770 35

The purpose of this investigation was to determine whether cardiovascular adaptations characteristic of long-term endurance exercise compensate more effectively during cardioselective beta(1)-adrenergic receptor blockade-induced reductions in sympathoadrenergic-stimulated contractility. Endurance-trained (ET) athletes (n = 8) and average-trained (AT; n = 8) subjects performed submaximal cycling exercise at moderate [45% maximum oxygen uptake (Vo(2max))] and heavy (70% Vo(2max)) workloads, with and without metoprolol. Cardiac output (Qc), heart rate (HR), and systolic blood pressure were recorded at rest and during exercise. Cardiac work was calculated from the triple product of HR, stroke volume, and systolic blood pressure, and myocardial efficiency is represented as cardiac work for a given total body oxygen consumption. Metoprolol reduced Qc at 45% Vo(2max) (P = 0.004) and 70% Vo(2max) (P = 0.022) in ET subjects, but did not alter Qc in the AT subjects. In ET subjects at 45% Vo(2max), metoprolol-induced reductions in Qc were a result of decreases in HR (P < 0.05) and the absence of a compensatory increase in stroke volume (P > 0.05). The cardiac work and calculated cardiac efficiency were reduced with metoprolol in ET subjects at both exercise intensities and in the AT subjects during the high-intensity workload (P < 0.01). The cardiac work and the calculated cardiac efficiency were not affected by metoprolol in the AT subjects during the 45% Vo(2max) exercise. Therefore, in AT subjects, beta-blockade reduced the amount of pressure generation necessary to produce the same amount of work during moderate-intensity exercise. In patients with heart disease receiving metoprolol, a decrease in the generation of cardiac pressure necessary to perform a given amount of work during mild-to-moderate exercise would prove to be beneficial.
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PMID:The effects of aerobic fitness and beta1-adrenergic receptor blockade on cardiac work during dynamic exercise. 1903 91

Coronary artery disease, stroke, and peripheral vascular disease are known as "atherothrombotic" manifestations of atherosclerosis. These devastating conditions remain the major contributor of mortality and disability in a modern Western world, with estimated direct and indirect cost for 403.1 billion dollars in the United States alone. The application of current evidence-based therapy including the administration of low-dose aspirin and standard of care with clopidogrel proved to exhibit absolute mortality reduction in the randomized clinical trials International Study for Infarct Survival and Clopidogrel and Metoprolol in Myocardial Infarction Trial among patients after acute vascular events. However, these established antiplatelet medications have certain shortcomings including lack of efficacy in some patients, significant response variability, and potential "resistance." Therefore, intelligent development of novel oral antiplatelet agents is difficult to underestimate. In this review, we will focus on the developmental efforts with regard to the experimental agents such as adenosine diphosphate receptor blockers (prasugrel, ticagrelor, and cangrelor) and platelet glycoprotein VI adhesion antagonist [ProCorde GmbH 15 (PR-15)].
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PMID:Novel antiplatelet agents in development: prasugrel, ticagrelor, and cangrelor and beyond. 1926 62


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