Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metoprolol and other beta-adrenergic blocking drugs are known to exert cardioprotective effects that include significant reduction in occurrence of ventricular fibrillation (VF) following myocardial ischemia and infarction. To help determine the mechanism of these cardioprotective effects, this study evaluated the effect of equipotent beta-blocking doses of metoprolol and three other beta-blockers with differing ancillary properties on ventricular fibrillation threshold (VFT) in the normal canine heart. Metoprolol tartrate (1.0 mg/kg i.v.), atenolol (0.3 mg/kg i.v.), propranolol hydrochloride (0.3 mg/kg i.v.), pindolol (0.03 mg/kg i.v.), or saline control (0.9% NaCl solution; vehicle) was given, alone and in combination with lidocaine (L), to groups of six pentobarbital (32.5 mg/kg i.v.) anesthetized mongrel dogs after control VFT and control isoproterenol-induced (ISO) positive chronotropic effects had been determined. The D- (membrane stabilizing, non-beta blocking) and L- (beta blocking) isomers of propranolol also were administered to separate groups of six anesthetized dogs in a dose of 0.3 mg/kg i.v. Blood samples (venous) were taken before drug or vehicle administration, 10 min after drug/vehicle administration and at half-hour intervals thereafter during experimentation. ISO responses and VFT were determined 5 and 15 min, respectively, after drug/vehicle administration and at half-hour intervals for a total experimental period of 165 min. VF was induced with a train of pulses (5 s, 100 Hz, 3-ms duration, 250-omega resistance) applied by bipolar platinum electrodes to a paced heart (200 beats/min). Voltage (V) was increased every 60 sec (0.25-V increments between 0-3.5 V and 0.5-V increments greater than 3.5 V) until VF occurred. Metoprolol increased VFT significantly (p less than 0.05) and maximally (max delta V = 2.3 +/- 0.7 V) at 135 min postdrug when the ISO-induced increase in heart rate was inhibited (%I ISO) by less than 53%. Max delta V was not significantly increased following i.v. administration of atenolol (0.8 +/- 0.6 V), pindolol (0.1 +/- 0.1 V), or saline (0.1 +/- 0.1 V). Max delta V was 0.5 +/- 0.2 in the D-propranolol-treated group and 0.5 +/- 0.3 in the L-propranolol-treated group. These values did not differ from max delta V obtained in the propranolol-treated group (0.6 +/- 0.4 V). Changes in VFT for all groups were, over time, negatively correlated with %I ISO and were not dependent on membrane stabilizing effect (metoprolol, propranolol (D,DL), pindolol), intrinsic sympathomimetic activity (pindolol), or cardioselectivity (metoprolol, atenolol).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of metoprolol, alone and in combination with lidocaine, on ventricular fibrillation threshold: comparison with atenolol, propranolol, and pindolol. 243 44

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.
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PMID:Effects of xamoterol on resting and exercise haemodynamics in patients with chronic heart failure. 257 50

Impaired left ventricular diastolic dysfunction is common in patients with ischaemic heart failure. The beta 1-adrenoceptor partial agonist xamoterol was compared with pindolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic activity, in a haemodynamic study in 17 patients with ischaemic heart disease. Pindolol caused left ventricular end-diastolic pressure, wall stress and T1 to rise, whereas xamoterol produced improvements in all three parameters. These results suggest that xamoterol may be of greater benefit to patients in heart failure.
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PMID:Contrasting effects of single doses of pindolol and xamoterol on left ventricular diastolic function. 257 64

The left ventricular sensitivity to sympathomimetic amines was assessed in 47 patients with ischemic heart disease and varying degrees of left ventricular dysfunction. Patients were divided into 3 subgroups according to their basal ejection fraction (less than or equal to 35%, between 36 and 54%, and greater than or equal to 55%). After injection of a bolus of isoproterenol (2 micrograms), the isovolumic indexes of inotropic state increased significantly less in patients with an ejection fraction less than or equal to 35% than in other patients, but the heart rate changes and the acceleration in the rate of isovolumic pressure fall were comparable in all subgroups. The dose-response curves to cumulative doses of xamoterol, a beta 1-adrenoceptor partial agonist, confirmed that the magnitude of the inotropic response was reduced during beta 1-stimulation in patients with an ejection fraction less than or equal to 35% when compared with patients with a greater ejection fraction. However, the dose of xamoterol necessary to produce 50% of the maximal inotropic response was not increased in patients with an ejection fraction less than or equal to 35% (range, 1.5-5.2 micrograms/kg; median 2.5 vs. median values of 2.3 and 3.3 micrograms/kg in the other subgroups; NS), and there was no shift to the right of the dose-response curve. It is concluded that in moderate ischemic heart failure, the magnitude of the inotropic response to isoproterenol or xamoterol is reduced. The absence of shift to the right of the dose-response curve to a beta 1-partial agonist suggests that this alteration in myocardial performance is not primarily caused by a decrease in beta-adrenoceptor responsiveness.
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PMID:Left ventricular sensitivity to beta-adrenoceptor-stimulating drugs in patients with ischemic heart disease and varying degrees of ventricular dysfunction. 282 Jun 12

To determine if intrinsic sympathomimetic activity (ISA) is associated with a hemodynamic advantage over non-ISA beta blockade, 17 patients with ischemic heart disease underwent resting echocardiography and symptom-limited stress radionuclide angiography on three occasions: control, pindolol (with ISA), 10 mg twice a day, and propranolol, 40 mg four times a day, in a nonrandomized design. In six patients with normal resting ejection fraction (EF) (mean = 57 +/- 4%), neither drug was associated with a significant hemodynamic improvement over control. In 11 patients with reduced resting EF (mean = 37 +/- 9%), pindolol was associated with a higher EF and peak velocity of circumferential fiber shortening at rest compared with propranolol but not control. On maximal exertion, pindolol was associated with a higher EF than that during control but was similar to propranolol. These observed beneficial effects on pindolol appear primarily to be related to the partial beta agonist activity which this agent possesses.
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PMID:The role of beta blockade, with and without intrinsic sympathomimetic activity, in preserving compromised left ventricular function in patients with ischemic heart disease. 285 72

The hemodynamic effects of acebutolol were studied in six patients with ischemic heart disease. The changes in heart rate, cardiac output, and arterial blood pressure were determined after intravenous administration of six increasing doses of acebutolol to a cumulative dose of 0.64 mg/kg. After the sixth dose of acebutolol, cardiac output and heart rate were reduced 15% and 8%, respectively. Pulmonary artery pressure was increased by 4 mm Hg. Arterial blood pressure was not changed significantly. The effects of graded doses of acebutolol on heart rate and cardiac output were compared with earlier obtained results after atenolol (0.19 mg/kg), pindolol (0.025 mg/kg), practolol (0.64 mg/kg), and propranolol (0.19 mg/kg). The effects of increasing doses of acebutolol and practolol were very similar and significantly different from the effects of the other three drugs in spite having been administered at equipotent doses. The hemodynamic effects of acebutolol support the hypothesis that the hemodynamic response to beta-adrenoceptor antagonist drugs at rest is determined primarily by the degree of intrinsic sympathomimetic activity, whereas beta-1 selectivity does not modify the central hemodynamic response.
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PMID:Immediate central hemodynamic effects of five different beta-adrenoceptor-blocking agents, acebutolol, atenolol, pindolol, practolol, and propranolol, in patients with ischemic heart disease. 285 78

Beta adrenoceptor blockade has become one of the major therapeutic interventions in the medical management of ischaemic heart disease over the last 15 years. A number of beta adrenoceptor blockers have been developed with differing pharmacological properties including cardioselectivity and intrinsic sympathomimetic activity (ISA). The relevance of this latter property has been in some doubt. A number of reports suggest that ISA confers haemodynamic benefits although there does not appear to be any clear therapeutic advantage. In addition it would appear that patients with severe or rest angina might benefit more from a pure beta antagonist rather than one with ISA when the beta blocker is used as monotherapy, but this situation rarely arises. This paper reviews and assesses the value of treatment of ischaemic heart disease with beta blockers possessing intrinsic sympathomimetic activity.
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PMID:Beta-adrenoceptor blockade and intrinsic sympathomimetic activity--relevance in the treatment of ischaemic heart disease. 286 81

Bevantolol hydrochloride, a beta adrenoceptor antagonist, can be categorized using conventional schemes as being cardioselective, devoid of intrinsic sympathomimetic activity and having weak membrane-stabilizing and local anesthetic properties. The cardioselectivity of bevantolol was conferred by the incorporation of a 3,4-dimethoxyphenyl moiety into the terminal amino portion of the molecule. This portion of the molecule also appears to account for bevantolol's in vitro binding affinity at alpha-adrenoceptor sites; the in vivo significance of which remains unclear. In the various cardiovascular disease-state models, bevantolol's profile differed from that of propranolol, i.e., there was no initial pressor response in spontaneously hypertensive or renal hypertensive rats. In a myocardial ischemia model, bevantolol, unlike propranolol, increased contractile function in the ischemic myocardium. A ring hydroxylated urinary metabolite, which occurred only in trace amounts in human urine, had an interesting profile when studied in animals at pharmacologic doses. It ranked high in cardioselectivity (like bevantolol), but unlike bevantolol showed significant intrinsic beta sympathomimetic activity. The clinical significance of this metabolite, if any, remains to be established. Collectively the preclinical profile of bevantolol showed it to have an interesting profile for a beta adrenoceptor antagonist in a variety of pharmacologic test systems.
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PMID:Bevantolol hydrochloride--preclinical pharmacologic profile. 287 86

The chemistry, pharmacology, pharmacokinetics, hemodynamic and electrophysiologic effects, clinical efficacy, adverse effects, drug interactions, compatibility and stability, dosage, and administration of esmolol hydrochloride are reviewed. Esmolol produces competitive blockade of beta receptors in both animals and humans. It does not possess membrane-stabilizing, intrinsic sympathomimetic, or alpha-adrenergic blocking activity. The relative cardioselectivity of esmolol is similar to that of metoprolol. Esterase metabolism accounts for the rapid total body clearance of 285 mL/kg/min and elimination half-life of 9.2 minutes. Its rapid metabolism following continuous intravenous infusion results in the rapid offset of pharmacologic effect after drug administration is discontinued. In patients with supraventricular tachyarrhythmias, esmolol produces rapid control of heart rate in an average effective dosage range from 97.2 to 115.0 micrograms/kg/min and effects that are similar to propranolol. Esmolol is effective and safe in managing tachycardia and hypertension during surgical stress and may be useful in postoperative hypertension or elevated heart rates during myocardial ischemia. Esmolol does not appear to interact with digoxin, morphine, warfarin, or succinylcholine to any clinically important extent. The most frequent adverse effects associated with esmolol infusion are hypotension and phlebitis. Hypotension can be avoided by careful titration, and if encountered, it can be rapidly resolved by dosage adjustment or discontinuation of the infusion. The ultrashort half-life and duration of action of esmolol may allow safer application of beta blockade in critically ill patients.
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PMID:Esmolol hydrochloride: an ultrashort-acting, beta-adrenergic blocking agent. 287 61

A new cardioselective beta 1-adrenoceptor partial agonist, xamoterol, has been developed for the treatment of heart failure, especially that associated with ischemic heart disease. To investigate the hemodynamic effect of xamoterol in relation to sympathetic nervous activity, hemodynamic variables and plasma norepinephrine (NE) levels were measured at rest and during three graded bicycle exercise tests before and after a single intravenous dose of 0.15 mg/kg xamoterol in 10 patients with mild-to-moderate left ventricular dysfunction. Plasma NE increased with increasing grade of exercise and a linear correlation between plasma NE and heart rate was observed at four time points (at rest and three exercise levels) before and after xamoterol. After administration of xamoterol, the slope of the regression line of plasma NE-heart rate relation was significantly less steep than that before drug. Predose and postdose regression lines crossed at 440 pg/ml of plasma NE. Similar effects were observed on the plasma NE-cardiac index and plasma NE-systolic blood pressure relations (regression lines crossed at 380 and 530 pg/ml of plasma NE, respectively). Thus, xamoterol had a dual agonist-antagonist effect in relation to plasma NE, and the crossover point lay approximately between 400 pg/ml and 500 pg/ml. This level of plasma NE was achieved at a low exercise level and at a heart rate of about 100 beats/min. These results indicate that xamoterol has intrinsic sympathomimetic activity comparable to relatively low sympathetic activity (400 to 500 pg/ml of plasma NE) and therefore acts as a beta 1-agonist when sympathetic nervous activity is below this level and as an antagonist when sympathetic activity is above this level.
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PMID:Hemodynamic effects of the beta 1-adrenoceptor partial agonist xamoterol in relation to plasma norepinephrine levels during exercise in patients with left ventricular dysfunction. 287 42


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