UMLS:C0038454 - FACTA Search

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

The goal of these experiments was to evaluate the effects of some drugs affecting noradrenergic (NE) synaptic transmission, commonly prescribed following stroke or traumatic brain injury, on functional recovery. Measurement of recovery from a transient hemiplegia produced by a traumatic unilateral focal contusion in sensorimotor cortex (SMCX) of rats was used to assess the effects of chronic haloperidol (HAL) treatment begun early (1 day) or late (18 days to recovered animals) after injury. Additionally, using the same model, the effects of a single administration of drugs with selective action at NE receptors were also evaluated early or late (30 days) after injury. These drugs were: phenoxybenzamine (PBZ), an alpha 1-NE antagonist; prazosin (PRAZ), an alpha 1-NE antagonist; yohimbine (YOH), an alpha 2-NE antagonist; propranolol (PROP), a beta 1- and 2-NE receptor antagonist; methoxymine (METHOX), an alpha 1-NE agonist; and clonidine (CLON), an alpha 2-NE agonist. The data indicate that drugs with antagonistic effects at alpha 1 NE receptors, including HAL and PRAZ but not PROP, administered early after SMCX contusion retard locomotor recovery. Beneficial effects of enhancing NE transmission by METHOX or YOH were not observed. In animals recovered from beam walk (BW) deficits, a single administration of PBZ or PRAZ (alpha 1 NE antagonists) or CLON (alpha 2 NE agonist) transiently reinstated hemiplegic symptoms. The nonspecific beta NE receptor antagonist PROP had no effect in recovered animals. A single dose of HAL had no effect in recovered animals, but a BW deficit transiently developed in some animals following chronic treatment. The data are discussed with reference to drug contraindications noted in clinical studies of recovery from poststroke aphasia and cognition in demented patients with degenerative brain disease.
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PMID:Norepinephrine and brain damage: alpha noradrenergic pharmacology alters functional recovery after cortical trauma. 216 17

The cardiovascular effects of three single intravenous doses of a beta 1-adrenoceptor partial agonist, xamoterol (0.025, 0.05 and 0.1 mg kg-1) and placebo were studied in six healthy volunteers at rest using a single-blind design. In addition to heart rate and blood pressure measurements, cardiac contractility was measured by means of M-mode echocardiography and systolic time intervals. Ambulatory 24 h Holter-monitoring of the electrocardiogram was performed. Plasma concentrations of xamoterol were measured. Compared to baseline, xamoterol (0.025 mg kg-1) increased heart rate (61 +/- 3-68 +/- 3 beats min-1, means and SEM) and systolic blood pressure (119 +/- 3-138 +/- 5 mm Hg) but decreased pre-ejection period (100 +/- 4-76 +/- 5 msec). Stroke volume (88 +/- 6-104 +/- 10 ml), cardiac output (4.8 +/- 0.4-6.6 +/- 0.61 min-1), velocity of circumferential fibre shortening (1.15 +/- 0.06-1.50 +/- 0.06 circ s-1) were increased by xamoterol. No significant changes were produced by placebo. No dose-dependent effects were seen and maximum effects were produced by 0.025 mg kg-1 xamoterol. Significant effects were observed for 2 h. The areas under the plasma concentration curves (AUC0-12) showed a linear dose response. No adverse effects attributable to xamoterol were seen in haematological, biochemical, urinalysis or electrocardiographic tests. Four volunteers were aware of a more forceful heart beat after xamoterol, but this was mild and transient. It is concluded that xamoterol has a positive inotropic action.
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PMID:The cardiovascular effects of xamoterol, a beta 1-adrenoceptor partial agonist, in healthy volunteers at rest. 242 51

The maximal increases in heart rate produced by intravenous xamoterol in anaesthetized cats and rats are less than that of (-)-isoprenaline. In cats, blood pressure was slightly raised, while in rats, supramaximal cardiac-stimulant doses produced reductions in blood pressure. In anaesthetized guinea pigs, cardiac-stimulant effects of xamoterol were evident only after treatment with hexamethonium. In all three species cardiovascular responses to xamoterol were antagonized by beta-adrenoceptor antagonists. Thus, xamoterol is a partial agonist which displays beta 1-adrenoceptor selectivity. In cats, infusions of xamoterol elicited beta-adrenoceptor-mediated increases in heart rate, blood pressure, and cardiac output, while calculated total peripheral resistance was little affected and, unexpectedly, stroke volume was reduced. These cardiovascular effects were unaffected by hexamethonium or captopril. Both xamoterol and (-)-isoprenaline elevated left ventricular dP/dtmax and reduced central venous pressure. When cat heart rate was paced over a range (175-250 beats/min) corresponding to the beta-receptor-mediated chronotropic effects, an inverse relationship between rate and stroke volume was observed. The rate-induced reduction in stroke volume offers the best explanation for the decrease in stroke volume produced by xamoterol. In general, the effects of beta-adrenoceptor agonists on stroke volume in the anaesthetized cat appear to represent a balance between a rate-related reduction and a drug-induced elevation of this parameter.
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PMID:Cardiovascular actions of xamoterol (ICI 118,587) in anaesthetized cats, rats, and guinea pigs. 242 70

Pharmacological and radio-ligand binding studies have recently indicated the existence of beta 2-adrenoceptors in the human heart. Their physiological role, however, remains to be elucidated. The present study investigated in 17 normal, young volunteers the effect on resting left ventricular (LV) function of two types of beta-blockers; a predominant beta 1-adrenoceptor antagonist (atenolol, 50 mg once daily) and ICI 118,551 (20 mg t.i.d.), a new, predominant beta 2-antagonist. LV function was assessed using M-mode echocardiograms and systolic time intervals. Atenolol, ICI 118,551, and placebo were given according to a randomized, double-blind, cross-over protocol. As compared with placebo, both drugs caused a decrease in resting heart rate, but the reduction by ICI 118,551 was less pronounced. Systolic blood pressure was only reduced by atenolol 8 mm Hg on average. Cardiac output was decreased to the same extent following treatment with atenolol (-20%) as after ICI 118,551 (-17%). These decreases in cardiac output were related to the beta-blocker-induced bradycardia, since stroke volumes were not affected during either selective beta 1- or beta 2-blockade. In addition, all other echocardiographic variables reflecting LV pump function, such as fractional shortening, velocity of diameter change and of displacements, pre-ejection period, and the ratio of PEP/LVET, were not different from placebo. We conclude that in normal young subjects, global LV pump function is not affected by beta 1- or by beta 2-blockade, despite the negative chronotropic effect of both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of beta 1- versus beta 2-adrenoceptor blockade on left ventricular function in humans. 242 84

Acebutolol is a relatively new beta-adrenoceptor blocking antagonist, possessing both beta 1-adrenoceptor selectivity and partial agonist activity (PAA). Its acute (24 h, 400 mg, twice daily) and long-term effects (3 weeks) on systemic and renal hemodynamics, body fluid volumes, hormones, and beta-adrenoceptor density on lymphocytes were studied in a single-blind placebo-controlled trial, in 10 hypertensive patients. The initial response to acebutolol (1-2 h) was a fall in heart rate (HR) (-9.6 +/- 2.7%), cardiac output (-16.0 +/- 3%), and stroke volume (SV) (-10.7 +/- 0.2%), and an increase in systemic vascular resistance (SVR) (18.0 +/- 3.9%). Mean arterial pressure (MAP) began to fall 2-3 h after dosing in parallel with a decrease in SVR. At the end of the acute study, MAP and SVR were decreased by 18.1 +/- 2.7% and 15.6 +/- 5.6%, respectively. By that time, HR and SV had returned to control values despite blockade of beta-adrenoceptors. After 3 weeks of treatment (mean dose of acebutolol 480 mg twice daily), the fall in MAP was 10.1 +/- 2.7% and HR was decreased by 13.0 +/- 2.3%. Renal blood flow and glomerular filtration rate did not change. Acute and long-term treatment had no effect on the density of lymphocyte-membrane beta-adrenoceptors. This could be explained by acebutolol's beta 1 selectivity or, alternatively, this could be due to the drug's PAA.
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PMID:Acute and long-term effects of acebutolol on systemic and renal hemodynamics, body fluid volumes, catecholamines, active renin, aldosterone, and lymphocyte beta-adrenoceptor density. 245 44

The pharmacological profile of nebivolol (N), a chemically novel beta-adrenergic antagonist, was assessed in investigations on isolated tissues, awake spontaneously hypertensive rats (SHR), closed-chest anesthetized dogs, and humans. In vitro, N was found to be a potent antagonist of beta 1-adrenergic receptors (A2 value, 5.8 X 10(-9) M) and only a weak beta 2-adrenergic antagonist (A2 value, 1.7 X 10(-6) M). The selectivity for the beta 1-adrenergic receptor was higher for N than for any of the reference compounds. In dogs--similarly with atenolol--N was more potent in blocking the isoprenaline (I)-induced increases in left ventricular performance than the I-induced decrease in arterial pressure. In dogs, as compared with propranolol, N (0.025 and 0.01 mg.kg-1 i.v.) increased cardiac output and stroke volume, lowered systemic vascular resistance, and had no significant effect on the variables related to left ventricular contraction. In contrast to other beta-adrenergic antagonists, N acutely lowered arterial blood pressure in SHR (1.25 mg.kg-1 i.p.) and in hypertensive patients (1 oral dose of 5 mg) for several hours. In healthy volunteers N (5 mg) lowered systemic vascular resistance during daily oral treatment and did not negatively affect left ventricular function. In conclusion, N is a potent and selective beta 1-adrenergic blocking agent with an interesting hemodynamic profile. In hypertensive subjects and SHR, a single dose lowers arterial blood pressure for substantial periods of time.
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PMID:Pharmacological and hemodynamic profile of nebivolol, a chemically novel, potent, and selective beta 1-adrenergic antagonist. 245 41

The hemodynamic and myocardial effects of chronic treatment (5 months) with converting enzyme inhibitor (CEI, enalapril, group T1, n = 10) or a beta 1 blocker (atenolol, group T2, n = 13) of normotensive mature male Wistar rats were studied and compared to untreated younger rats (group C0, 11 months old, n = 14) and to untreated age-matched controls (group C1, 16 months old, n = 14). Heart rate was significantly decreased in T2 rats but unchanged in the T1 group. There was a significant decrease in systolic and diastolic arterial blood pressure (BP) in both treated groups (systolic T1:90 +/- 17, T2: 87 +/- 10, vs. C1: 102 +/- 11 mm Hg, and diastolic T1: 60 +/- 17, T2: 59 +/- 9, vs. C1: 73 +/- 13 mm Hg). Cardiac output was unchanged by therapy but stroke volume was significantly increased in the T2 group (0.24 +/- 0.03 vs. 0.19 +/- 0.04 cm3 in C1). Total peripheral resistance was significantly decreased in T1 and T2 groups. Left ventricular weight to body weight ratio (LVW/BW) was significantly decreased in T1 (1.74 +/- 0.11 vs. 2.02 +/- 0.22 in C1) but unchanged in T2 (1.90 +/- 0.15 vs. 2.02 +/- 0.22). The left ventricular passive pressure-volume curve was significantly rightward shifted by beta-blocker therapy (T2) but unchanged by CEI (T1). This corresponds to a decrease of chamber stiffness k in the T2 group compared to C1 and T1 groups. A significant fibrosis was seen in group T2 (mean collagen fiber thickness of 3.03 +/- 0.24 vs. 2.8 +/- 0.15 micron) but not in the T1 group (2.94 +/- 0.14 vs. 2.8 +/- 0.15 micron). Thus, despite the similar decrease in BP induced by the CEI and the beta blocker, the cardiac effects of the two drugs were opposite: CEI decreased LVW/BW with no change in the left ventricular pressure-volume curve and myocardial fibrosis whereas beta blocker did not change the LVW/BW, but induced a left ventricular dilation associated with a decrease in chamber stiffness and an increase in subendocardial fibrosis.
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PMID:Long-term cardiac effects of hypotensive agents in normotensive mature rats: comparison of beta-blocking agent and converting enzyme inhibition. 247 16

The pyridazoline derivative UDCG 115 BS (pimobendane) is a new, noncatecholamine, nonglycoside inotropic compound with potent vasodilative properties which exerts its stimulatory myocardial effect by increasing the Ca2+ affinity of cardiac contractile proteins and thus improving Ca2+ utilization. The aim of this study was to characterize and quantify the hemodynamic profile of oral UDCG 115 BS in 25 patients suffering from idiopathic congestive cardiomyopathy (NYHA III) and compare these effects with the action of the beta 1-receptor agonist dobutamine. UDCG 115 BS 5 mg p.o. increased cardiac output, cardiac index, and stroke volume index by approximately 60%. With only minor changes in heart rate, ventricular filling pressures decreased by 40%. A decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressures (-35%) were also observed. The effects of 5 mg UDCG 115 BS were comparable to those that occurred with the optimal dose of dobutamine, whereas 10 mg UDCG 115 BS induced significantly more pronounced hemodynamic changes. The effects of UDCG lasted for at least 12 h. No major side effects were observed. Continuous treatment with 10 mg UDCG 115 BS/day for greater than 5 days resulted in a significantly improved response in beta-adrenoceptor stimulation as well as a drop in endogenous plasma catecholamines to nearly normal values. We therefore conclude that UDCG 115 BS, with its unique receptor-independent mechanism of action, may represent a new therapeutic approach in the management of patients with congestive heart failure (CHF).
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PMID:Cardiovascular profile of UDCG 115 BS-pimobendane and reversibility of catecholamine subsensitivity in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy. 247 21

The pyridazoline derivative UD-CG 115 BS (pimobendan) is a noncatecholamine, nonglycoside new inotropic compound with potent vasodilator properties that exerts stimulatory myocardial effects by increasing the Ca2+ affinity of cardiac contractile proteins, thus improving Ca2+ utilization. The aim of the present study was to characterize and quantify the hemodynamic effects of oral UD-CG 115 BS in 25 patients with idiopathic congestive cardiomyopathy (NYHA stage III) and compare these to the action of the beta 1-receptor agonist dobutamine. UD-CG 115 BS 5 mg p.o. increased cardiac output, cardiac index, and stroke volume index by approximately 60%. With only minor changes in heart rate, ventricular filling pressures decreased (-40%) and there was a decline in pulmonary and systemic vascular resistance (-50%), as well as in systolic, diastolic, and mean pulmonary artery pressure (-35%). The effects of 5 mg UD-CG 115 BS were comparable to the optimal dose of dobutamine, while 10 mg induced significantly more pronounced hemodynamic changes. The effects of UD-CG 115 BS lasted for at least 12 h. No major side effects were observed. A continuous treatment with 10 mg of UD-CG 115 BS/day over a period of 5 days resulted in a significantly improved response to beta-adrenoceptor stimulation while endogenous plasma catecholamines fell down to nearly normal values. It is concluded that UD-CG 115 BS, with its unique receptor independent mechanism of action, may represent a new therapeutic approach for management of congestive heart failure patients.
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PMID:Clinical efficacy of pimobendan (UD-CG 115 BS) in patients with chronic congestive heart failure. 247 88

The known properties of xamoterol, a partial beta 1-agonist, provide a basis to pharmacologically modulate cardiac responses to variations in sympathetic tone. Haemodynamic variables were assessed at rest and on exercise before and after intravenous xamoterol (0.2 mg kg-1), in 30 patients with mild to moderate cardiac failure. Xamoterol produced significant improvements in resting cardiac index (2.51 +/- 0.15 to 2.80 +/- 0.14 l min-1 m-2; P less than 0.001), stroke volume (62 +/- 4 to 75 +/- 5 mljbeat-1; P less than 0.001) and stroke work index (42.4 +/- 3.6 to 47.7 +/- 3.9 gm beat-1 m-2; P less than 0.01). This occurred despite a significant reduction in heart rate (78 +/- 3 to 74 +/- 2 beats min-1; P less than 0.05). There were also significant reductions in systemic vascular resistance (1990 +/- 141 to 1669 +/- 112 dynes s-1 cm-5; P less than 0.01) and double product (1146 +/- 46 to 1051 +/- 41 mmHg min-1 x 10(-1); P less than 0.05), with no significant changes in systolic blood pressure, pulmonary wedge pressure or ejection fraction. Xamoterol significantly attenuated the heart rate response to exercise (112 +/- 4 to 97 +/- 3 beats min-1; P less than 0.001), with no impairment in the expected exercise induced increase in cardiac index. This was due to the significant increase in stroke volume from 81 +/- 6 to 95 +/- 7 ml beat-1 (P less than 0.001). There were no significant changes in resting or exercise noradrenaline levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The acute effects of intravenous xamoterol ('Corwin', I.C.I. 118, 587) on resting and exercise haemodynamics in patients with mild to moderate heart failure. 256 33

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