Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In animals without myocardial infarction the new beta-sympathicolytic agent atenolol (4-[2'-hydroxy-3'-iso-propylaminopropoxy]-phenyl acetamide, ICI 66 082) dose-dependently decreased heart rate, systolic aortic pressure and cardiac output. Coronary mean flow, coronary resistance, stroke volume, left ventricular enddiastolic pressure and total peripheral vascular resistance did not change significantly. Atenolol significantly reduced myocardial contractility, expressed by (dp/dtmax), Vpm, t-(dp/dtmax) and pre-ejection period. Furthermore, the comparative studies in animals with myocardial infarction and concomitant reduced cardial efficiency revealed, that atenolol has neither a positive intrinsic activity as has practolol nor a negative intrinsic activity as has propranolol. The dose-contractility relation of atenolol resembles that of practolol: in low dosages a strong decrease is achieved, in higher dosages no further reduction of the contractility parameters is observed. Because of the strong negative inotropic and blood pressure lowering effect it is suggested to use atenolol only with great caution in patients with reduced cardiac efficiency.
 ...
PMID:[The effect of atenolol on contractility and hemodynamics of the infarcted heart in comparison to propranolol and practolol (author's transl)]. 124 85

The diameters of pial arterioles of mice were monitored in vivo with an image-splitting technique and television microscopy. Concentrations of leukotriene C4 as low as 10(-7) M constricted the arterioles. The leukotriene C4-D4 receptor blocker ICI 198615 (10(-8) M) inhibited the response. Endothelial injury by helium-neon laser/Evans blue technique eliminated the constriction and unmasked a slight but consistent relaxation that was not inhibited by 10(-8) M ICI 198615. Since leukotrienes are produced by the brain and enter the cerebrospinal fluid in ischemia, head trauma, and subarachnoid hemorrhage, the possibility that leukotrienes C4 and D4 contribute to decreases in cerebral blood flow during these conditions should be considered. However, the present data makes such a possibility far less likely because the endothelium is frequently injured in these conditions, and therefore the ability of leukotrienes to constrict vessels would be severely curtailed.
Stroke 1990 Nov
PMID:Leukotriene constriction of mouse pial arterioles in vivo is endothelium-dependent and receptor-mediated. 217 72

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)
 ...
PMID:Influence of beta 1- versus beta 2-adrenoceptor blockade on left ventricular function in humans. 242 84

1. A bicycle exercise test was used to investigate functional capability and haemodynamics in 30 patients with heart failure (13 NYHA Class II, 17 Class III), before and after i.v. xamoterol (Corwin, Carwin, Corwil, Xamtol, ICI 118,587) 0.2 mg kg-1. 2. Resting heart rate fell from 78 to 74 beats min-1 (P less than 0.05) and cardiac index rose from 2.5 to 2.8 l min-1 m-2 (P less than 0.001) after xamoterol. Blood pressure fell slightly, and systemic vascular resistance was reduced. Stroke work index improved and double product decreased. There were no changes in pulmonary artery wedge pressure ejection fraction or plasma noradrenaline concentrations. 3. On exercise, xamoterol produced a considerable reduction in heart rate increase, improved stroke volume and left ventricular stroke index and lowered double product. Exercise duration increased by 10%, but this did not quite achieve statistical significance. 4. These results are consistent with the concept that a beta 1-partial adrenoceptor agonist with the level of intrinsic sympathomimetic activity (43%) of xamoterol provides moderate inotropic support at rest, and protects the heart against overstimulation on exercise, when sympathetic drive is high. 5. Reduction of double product on exercise implies a lowered oxygen demand, which could be of considerable importance in patients with ischaemic heart disease.
 ...
PMID:Effects of xamoterol on resting and exercise haemodynamics in patients with chronic heart failure. 257 50

The effects of acute intravenous administration of ICI 118,587 (Corwin), a partial beta 1 agonist, were studied in nine patients with dilated cardiomyopathy and symptomatic congestive heart failure. Hemodynamic and metabolic parameters were measured using Swan-Ganz, arterial, and coronary sinus catheters. Repeated doses of Corwin produced no significant change in left ventricular performance, while a trend towards decreased blood pressure and stroke work was seen. No change occurred in coronary sinus blood flow, transmyocardial lactate extraction, or catecholamine release. One patient had significant depression of left ventricular function with hypotension. Thus, acute infusion of Corwin produced no beneficial inotropic responses, but rather produced features suggestive of further myocardial depression.
 ...
PMID:Acute hemodynamic and metabolic effects of ICI 118,587 (Corwin), a selective partial beta 1 agonist, in patients with dilated cardiomyopathy. 286 73

ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous administration of four sequential doses (0.5, 0.5, 1.0 and 2.0 mg) of ICI 141,292 was examined. HR decreased 7% (P less than 0.05) following ICI 141,292 1 mg with no further decrease following the succeeding doses. Cardiac output decreased 5.2% (P less than 0.05) following a cumulative dose of 4 mg. No significant changes were observed in mean arterial blood pressure, stroke volume or total peripheral resistance whereas an increase in supine resting mean pulmonary arterial pressure of 3.4 mm Hg (P less than 0.05) could be demonstrated. ICI 141,292 seems to be a potent (at least five times as potent as atenolol) beta 1-adrenoceptor blocking agent possessing moderate intrinsic sympathomimetic activity.
 ...
PMID:Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease. 288 Jun 3

Central hemodynamic responses evoked by standardized hemorrhage (exsanguination of 20 ml x kg bwt-1) were followed during 2 h in cats with intact and blocked vascular beta 2-adrenoceptors using the 'selective' beta 2-blocker, ICI 118, 551. In the first 10 min after bleeding blood pressure and cardiac output (CO) decreased and total peripheral resistance (TPR) increased by the same amount in the 'intact' and beta 2-blocked animals. Whereas blood pressure later on reached approximately the same hypotension level in both groups, other hemodynamic variables were distinctly different. In the 'intact' animals there was a gradual, partial recovery of stroke volume (SV) and CO in the face of a restoration to control of TPR. In the beta 2-blocked animals TPR continued to increase in the face of a maintained low CO and declining SV. The lower SV in the latter group was ascribed to abolition of beta 2-adrenergic restoration of plasma volume via absorption of tissue fluid into the circulation. The gradual decline of TPR in the 'intact' animals was attributed to beta 2-adrenergic dilator interaction with constrictor influences on the resistance vessels. It is concluded that beta-adrenergic vascular control mechanisms help to improve nutritional tissue blood flow during hemorrhage by increasing plasma volume, and hence venous return and CO, and by decreasing TPR. These reflex, beta 2-adrenergic circulatory events are similar to those aimed at in current shock therapy by transfusion and vasodilator treatment.
 ...
PMID:Influences on central hemodynamics in hemorrhage of beta 2-adrenergic vascular control mechanisms. 613 20

The haemodynamic effects at induction of anaesthesia with ICI 35 868 (1.5 mg/kg) are reported in ten patients with severe aortic or mitral valve disease. The average decrease of mean arterial pressure was 19.1% (p less than 0.01), heart rate decreased by 10% (p less than 0.01). Cardiac index and stroke volume index were both little changed but there were significant reductions in rate pressure product and left ventricular stroke work index (p less than 0.01).
 ...
PMID:The cardiorespiratory effects of ICI 35 868 in patients with valvular heart disease. 633 54

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows sinus node rate. Its effects on haemodynamic function have been studied in pentobarbitone anaesthetized dogs, in comparison with zatebradine, atenolol and nitrendipine. 2. ZD7288 lowered heart rate in the dose-range 0.02 to 1.0 mg kg-1 i.v. from 152 to 77 beats min-1. Myocardial contractile function (measured as both dPLV/dtmax and right ventricular free wall developed force) decreased along with rate. Stroke volume increased as rate decreased. Cardiac output decreased at doses in excess of 0.2 mg kg-1, i.v. 3. These haemodynamic changes were reversed when heart rate reduction was reversed by atrial pacing and are, therefore, considered to be indirect consequences of heart rate changes induced by ZD7288. 4. The effects of zatebradine paralleled those of ZD7288 (heart rate reduced from 149 to 60.5 beats min-1 over the dose-range 0.02 to 1.0 mg kg-1, i.v.), except that dPLV/dtmax did not decrease with heart rate and increased during arial pacing. 5. Neither ZD7288 nor zatebradine had significant effects on atrio-ventricular conduction at intrinsic heart rates, but both significantly and dose-dependently prolonged the atrio-ventricular conduction interval during atrial pacing at 180 beats min-1. 6. The observed effects of atenolol were commensurate with removal of beta-sympathetic cardiac drive. Atrial pacing was found not to restore the pre-atenolol heamodynamic state completely. 7. Nitrendipine up to 0.2 mg kg- i.v. induced changes indicative of direct vasodilatation accompanied by reflex compensation, followed by cardiac depression at higher doses. Atrial pacing failed to compensate for the effects of vasodilatation, but caused atrio-ventricular conduction block at doses above 0.5mgkg-1, i.v.8.data show ZD7288 has marked heart rate slowing properties and that accompanying haemodynamic changes appear to be secondary to the rate changes, being reversed by atrial pacing even in the continued presence of the drug. Heart rate slowing without depression of contractile function should prove to be of benefit in the treatment of myocardial ischaemia, particularly in the presence of myocardial dysfunction.
 ...
PMID:Haemodynamic actions of a novel sino-atrial node function modulator, ZENECA ZD7288, in the anaesthetized dog: a comparison with zatebradine, atenolol and nitrendipine. 785 50

1. ZENECA ZD7288 (4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride, formerly ICI D7288) is a novel sino-atrial node function modulator which selectively slows heart rate. 2. The haemodynamic effects of ZD7288 (0.1, 0.3 and 1.0 mg kg-1, i.v.) have been evaluated and compared with those of placebo (physiological saline), zatebradine (ULFS 49, 0.1, 0.3 and 1.0 mg kg-1, i.v.) and propanolol (0.03, 0.1, and 0.3 mg kg-1, i.v.) in beagles chronically instrumented for measurement of heart rate, aortic pressure, aortic flow and dPLV/dtmax. The dogs were trained to run at 6.5 k h-1 on a level treadmill for 5 min at half hourly intervals over a period of 4 h. Drugs were dosed cumulatively after the second, fourth and sixth exercise periods. 3. Control experiments demonstrated a degree of accommodation to repeated exercise over a period of 4 h. Resting heart rate decreased by 21 beats min-1, but heart rate response to exercise was maintained, whereas dPLV/dtmax at rest remained steady while the response to exercise decreased significantly (by 25% after 2 h, P < 0.05). 4. ZD7288 and zatebradine both decreased heart rate during exercise in a dose-dependent manner, whilst heart rate at rest did not differ from resting heart rates in saline dosed control animals. In contrast, heart rate at rest and during exercise were lowered equally by the lowest doses of propranolol (approximately by 30 beats min-1), and additional doses caused only minor additional decreases. The exercise-induced tachycardia was maintained within 12% of pre-dose levels, presumably by withdrawal of vagal tone.5. Cardiac inotropism, as indicated by dPLv/dt max, was not affected by ZD7288 or zatebradine at rest,although the inotropic response to exercise decreased in proportion to the decreases in exercise-induced tachycardia. Propranolol caused a marked dose-dependent decrease in the exercise-induced inotropic response (by 85% at 0.3mg kg-1).6. Whilst the sino-atrial node modulators increased stroke volume at rest, and augmented increases in response to exercise, propranolol did not affect resting stroke volume and decreased the responses to exercise.7. Cardiac output at rest and cardiac output increases during exercise were well maintained in the presence of ZD7288 and zatebradine in contrast to propranolol which induced a significant depression of cardiac output, both at rest and during exercise. Propranolol also caused significant systemic vasoconstriction.8. In conclusion, ZD7288 has haemodynamic actions comparable to those of zatebradine despite their chemical dissimilarity. ZD7288 may be of benefit in the treatment of ischaemic heart disease by reducing heart rate without impairing cardiac function.
 ...
PMID:The haemodynamic actions of ZENECA ZD7288, a novel sino-atrial node function modulator, in the exercising beagle: a comparison with zatebradine and propranolol. 785 51


1 2 3 4 Next >>