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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of a new selective beta1 partial agonist, ICI 118,587, on cardiac function were assessed in clinical settings. In 7 patients, responses to multistage treadmill exercise were studied before and after an acute intravenous injection of the drug. The heart rate and blood pressure were not altered by ICI 118,587 at rest but increases in both parameters in response to exercise were significantly reduced. Neither oxygen consumption nor plasma norepinephrine level was modified by the drug both at rest and during exercise. The long term effects of ICI 118,587 were assessed in 6 patients with mild to moderate cardiac failure consequent upon ischemic heart disease. After chronic administration of the drug exercise duration was increased. The symptom-limited maximal oxygen consumption increased by 16%, associated with prolongation of the exercise tolerance. In those patients who also had symptoms of angina pectoris, exercise levels which caused angina during the control study were tolerated without symptoms after ICI 118,587. Twelve patients with nocturnal bradycardia resulting from atrial fibrillation of sick sinus syndrome were treated with ICI 118,587. Monitoring of heart rate by 24-hour Holter ECG showed that ICI 118,587 increased minimal heart rate during sleep. Being a beta1-adrenoceptor partial agonist, it has both agonist and antagonist properties. Thus, ICI 118,587 buffers the heart from an excessively low sympathetic tone which may occur during sleep and from an excessively high tone during exercise. It appears to be of benefit in the treatment of mild to moderate cardiac failure consequent upon ischemic heart disease. It also improves oxygen demand-supply imbalance without inducing further myocardial depression or inappropriate bradycardia at rest. ICI 118,587 may therefore be described as a cardiostabilizer.
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PMID:Cardiovascular effects of ICI 118,587, a new beta-adrenoceptor partial agonist in man. 287 3

The receptor pharmacology of the cardiovascular effects of dopexamine hydrochloride in the anaesthetized dog (given by i.v. infusion of 3 X 10(-9)-10(-7) mol kg-1 min-1) has been analysed by the use of selective receptor antagonists and of ganglionic blockade. The increases in cardiac output, contractility, and rate were antagonized by the beta 2-adrenoceptor antagonist, ICI 118551. Renal blood flow rose secondary to reduction in renal vascular resistance and this was antagonized by SCH 23390, a highly selective DA1-receptor antagonist. Peripheral vasodilation and reduction of blood pressure were mediated by a combination of DA1- and DA2-receptor and beta 2-adrenoceptor stimulation. In a separate group of dogs, the cardiac stimulant effects of dopexamine HCl were partially reflex and were reduced by ganglion block, revealing responses due to stimulation of cardiac beta 2-adrenoceptors. Thus the beta 2-adrenoceptor agonist action of dopexamine HCl is not only partly responsible for afterload reduction but also leads to direct cardiac stimulation. From its cardiovascular profile, dopexamine HCl is likely to be of use in acute treatment of heart failure.
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PMID:The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and beta 2-adrenoceptors in the dog. 288 55

The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use result, in the first place, from an insufficient understanding of their mechanism of action. Some of them (pirbuterol, salbutamol, terbutaline, penoterol) seem to act preferentially on B2 adrenergic receptors and the haemodynamic effect results, in part or predominantly, from the vasodilator action which they cause. On the other hand, other agents (prenalterol, ICI 108-87) show a relative selectivity for B1 adrenergic receptors. Ibopamine exerts its action on B1 receptors and dopaminergic receptors. A second problem concerns the hypothetical character of their long term therapeutic activity. A major problem in the use of several of these sympathomimetic agents in chronic treatment is the appearance of a desensitization of the beta receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New cardiotonic agents]. 293 98

The haemodynamic effects of a new beta 1-adrenoceptor partial agonist, ICI 118,587, were studied in 10 patients with dilated cardiomyopathy and moderate to severe cardiac failure. Simultaneous right and left heart catheterisations were performed. Resting central haemodynamic indices were measured before and 15 min after an intravenous dose of 0.05 mg/kg and then 15 min after an additional intravenous dose of 0.15 mg/kg of ICI 118,587. Left ventricular performance was improved--as shown by significant increases in systolic left ventricular pressure, maximum rate of rise in left ventricular pressure (dP/dt max), and cardiac output and a decrease in left ventricular end diastolic pressure--without an undesirable increase in heart rate. The top of the dose response curve was reached after the lower dose. An important unwanted effect was seen in the most severely diseased patient, whose left ventricular systolic pressure, dP/dt max, and cardiac output decreased. This was probably due to the drug's antagonistic property supervening in this patient, who probably had high concentrations of circulating catecholamines. It is concluded that ICI 118,587 has a positive inotropic action and improves cardiac performance in patients with dilated cardiomyopathy and moderate cardiac failure, although care should be exercised when the drug is given intravenously in severe failure.
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PMID:Haemodynamic effects of ICI 118,587 in cardiomyopathy. 614 36

Effect of ICI 118,587 (corwin, ICI), a new cardioselective beta-partial agonist, on left ventricular (LV) function was studied and compared with that of isoproterenol and propranolol in 10 conscious normal dogs, instrumented with a micromanometer and pairs of ultrasonic crystals for analysis of LV wall motion. Heart rate, LV dP/dt and mean circumferential shortening velocity were measured at rest and during 3 levels of treadmill exercise (Ex). Before drug administration (control), the heart rate, dP/dt, percent shortening and mean circumferential shortening velocity were enhanced linearly along with the graded Ex. The Ex response curve shifted upward during isoproterenol infusion and downward after the administration of propranolol. With ICI, hemodynamic and contractile indexes were enhanced at rest as with isoproterenol, while these indexes were depressed during maximal Ex as after propranolol. The Ex response curve after ICI crossed the control response curve at a moderate level of Ex. Thus ICI exerts positive inotropic and chronotropic effects at rest when basal sympathetic tone is low, whereas it exerts negative inotropic and chronotropic properties at maximal Ex when sympathetic tone is high. The inherent dual action of this drug is expected to open a new field of treatment for ischemic heart disease with or without heart failure.
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PMID:Effect of ICI 118,587 on left ventricular function during graded treadmill exercise in conscious dogs. 614 83

Patients with progressive muscular dystrophy rarely survive beyond the second or third decades: the commonest causes of death are respiratory failure and cardiac failure. An easily repeatable method for early recognition of cardiac dysfunction and its follow-up would therefore be valuable. We performed a polycardiographic study of systolic time intervals in 11 patients with dystrophy (each subject representing an age from 7 to 17 years) in a group comprising 10 of their mothers and in control groups matched for age and sex. The mean values of QS2, PEP and QS1 were significantly higher in patients compared to controls (QS2 : 543 +/- 26 msec compared to 519 +/- 19 msec; PEP : 142 +/- 21 msec compared to 123 +/- 18 msec, and QS1 : 105 +/- 22 msec compared to 75 +/- 12 msec) whilst mean ICT was shorter (36 +/- 11 msec, compared to 49 +/- 5 msec). Mean LVET was comparable in patients and control. These results indicate a reduction in compliance and an increase in end diastolic left ventricular tension. When the systolic time intervals were analysed in each child, an increase in PEP and reduction in LVET were characteristic of the more serious phases of the disease with cardiac failure. It is emphasized that early stages of the disease are characterised by restrictive changes resulting in a reduction in ICT whilst terminal stages with reduced cardiac output cause a reduction in LVET and an increase in PEP. No significant changes were found in the mothers of patients compared to the control group. These results indicate that systolic time intervals may be useful in following up patients with Duchenne's cardiomyopathy.
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PMID:[Evaluation of systolic intervals in Duchenne cardiomyopathy]. 681 20

Alcohol decreases myocardial contractility through direct, toxic effect. Ingestion of more than 150 g per day for more than 10 years carries a high risk of developing alcoholic cardiomyopathy. The discontinuance of alcohol intake--if put into effect early in the natural history of patients with alcoholic cardiomyopathy--commonly but not invariably results in remission of heart failure. In order to evaluate the left ventricular (LV) function and to find out a possible correlation between the degree of cardiac dysfunction and the severity of the morpho-functional aspects of alcoholic liver disease, 20 chronic alcoholic patients without clinical evidence of heart disease were examined. Echocardiography, systolic time intervals, mechanical polygraphic recordings and liver biopsy were obtained. According to the morphological alterations showed by the needle biopsy of the liver, we separated 12 patients with liver steatosis (Group I) from 8 subjects with alcoholic hepatitis and fibrosis. In Group I LVET, ICT, PEP/LVET indices and LV fractional shortening (delta %) were not statistically different from control subjects. Patients of Group II showed marked impairment of myocardial function, as revealed by significant ICT, PEP, PEP/LVET prolongation and by an equally significant reduction of fractional shortening of the LV. The noninvasive method has proved to be quite useful in detecting early LV dysfunction in asymptomatic chronic alcoholics and has revealed a correlation between the severity of the morphological involvement of the liver and the impairment of cardiac performance.
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PMID:[Non-invasive evaluation of left ventricular function in chronic alcoholics. Histo-morphological and echo-polygraphic correlations]. 718 10

The effects of intravenous disopyramide phosphate on myocardial function were evaluated by non-invasive indices of cardiac performance (systolic time intervals, STI) in 15 patients with atherosclerotic heart disease and different degrees of cardiac failure. Disopyramide (1.5 mg/Kg) was given intravenously over a period of 5 min. This drug induced in patients in I-II classes of NYHA a significant decrease of LVETc, while PEP, ICT, and PEP/LVET ratio rose significantly. STI were affected much more markedly in patients in III-IV classes of NYHA. Particularly affected were contractility indices (PEP, ICT, PEP/LVET), which were reduced significantly more in patients in III-IV classes as compares to patient in I-II classes. In contrast, LVETc, which correlates to stroke volume and cardiac output, was similarly worsened by the drug in the 2 groups of patients. Therefore, this study shows that disopyramide has relevant depressant effects on myocardial performance, simultaneously reducing stroke volume and contractility, and that the effect on contractility is more marked in patients with severe left ventricular impairment.
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PMID:Effects of intravenous disopyramide on myocardial function in patients with different degrees of cardiac failure. 737 60

We have shown previously that right heart failure (RHF) in dogs is associated with activated endogenous opiate systems, and that administration of the opioid receptor antagonist, naloxone, increases arterial pressure, cardiac contractile function and organ blood flows. To study whether the cardiovascular effects of naloxone are mediated via the mu- or delta-opioid receptors, we administered ICI-154,129, a delta-receptor antagonist, and naloxonazine, a mu-receptor antagonist, to 10 conscious dogs with RHF on 2 separate days. Like naloxone, ICI-154,129 increased mean aortic pressure, cardiac output, peak positive first derivative of left ventricular pressure, and blood flows to the myocardium, kidneys, splanchnic beds, and skeletal muscle. These changes were associated with increases in plasma epinephrine and norepinephrine. In contrast, naloxonazine had no effects on systemic hemodynamics, regional blood flow distribution, and plasma catecholamines in RHF. These findings suggest that the increased endogenous opioids during heart failure act on the delta-opioid receptors to decrease myocardial mechanical performance and alter regional blood flow distribution. Opioid receptor-blocking agents may exert beneficial cardiovascular effects in heart failure.
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PMID:Comparison of cardiovascular effects of mu- and delta-opioid receptor antagonists in dogs with congestive heart failure. 809 95

The present study was aimed to characterize the effects of epinine, the metabolite of the p.o. active dopamine derivate ibopamine in human cardiovascular tissues such as myocardium, coronary artery and pulmonary artery. Isometric force of contraction was studied in electrically driven papillary muscle strips from nonfailing (brain death), moderately failing (New York Heart Association class II-III, mitral valve replacement) and terminally failing human myocardium (New York Heart Association class IV, heart transplants) as well as in auricular trabeculae (aortocoronary bypass operation). Epinine increased force development in a concentration-dependent manner. In comparison to isoprenaline, epinine had a significantly lower potency but a similar efficacy to enhance force of contraction. Depending on the degree of myocardial failure, the effectiveness of epinine was reduced, whereas the potency was similar. Only in nonfailing myocardium, epinine increased force of contraction as effectively as Ca++. Prestimulation with forskolin or milrinone enhanced the potency of the epinine-mediated inotropic effect. In contrast, the beta-1-selective antagonist CGP 207.12A [2-hydroxy-5-(2-(hydroxy-3-(4-((1-methyl-4-trifluoromethyl)-1-H-imidazol -2-yl)-phenoxy)-propyl)-aminoethoxyl)-benzamide] and the beta-2-selective antagonist ICI 118.551 [erythro-(+-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride] shifted the concentration-response curve of epinine significantly to the right, indicating action at both beta-2 and beta-1 adrenoceptors. Epinine exerted higher affinity at beta-2 compared to beta-1 adrenoceptors in radioligand binding experiments ([125I]iodocyanopinodolol). In human coronary artery rings and pulmonary artery rings epinine alone as well as epinine in the presence of propranolol initiated a concentration-dependent increase in tension development in precontracted (prostaglandin F2 alpha, 0.3 mumol/l) as well as in non-precontracted rings. These results suggest that epinine exerts no direct vasodilatory activity in human coronary and pulmonary arteries at concentrations which are capable to produce positive inotropic activity. The supposed beneficial effects of ibopamine in the treatment of heart failure may not be due to positive inotropic actions as the concentrations producing positive inotropy are much higher than the clinically observed plasma concentrations.
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PMID:Cardiac inotropic as well as coronary and pulmonary artery actions of epinine in human isolated tissues. 838 40


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