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

The various antihypertensive agents reduce blood pressure by different mechanisms. Alpha-1 receptor blockers reduce vascular resistance and maintain cardiac output. Chronic treatment with beta blockers without intrinsic sympathomimetic activity produces a fall in blood pressure which is associated with a fall in cardiac index and heart rate. Beta blockers with strong intrinsic sympathomimetic activity showed reduced heart rate during exercise. Labetalol reduces cardiac output and peripheral vascular resistance with little or no reduction in peripheral blood flow. Alpha-1 blockers are suitable for patients with active life-styles, with peripheral vascular disorders, or with high blood-cholesterol levels. Beta blockers are useful in patients who have tachycardia, palpitation problems, or angina pectoris, or who have survived a heart attack. They should not be used in patients with bronchial asthma, reduced peripheral blood flow, or heart failure. Labetalol reduces blood pressure in a somewhat larger fraction of patients than the pure alpha- or beta-blocking agents. It is hoped that its long-term results will include regression of cardiovascular damage, improved quality of life, and increased life expectancy.
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PMID:The hemodynamic effects of adrenergic blocking agents. 135 Feb 35

Carvedilol, a new beta-blocker with vasodilating properties due to alpha 1-blockade, was investigated in preparations of human ventricular myocardium. Carvedilol demonstrated a high affinity and is a slightly beta 1-selective competitive beta-blocking agent, with a KD for beta 1-receptors of approximately 4-5 nM and a mild selectivity for beta 1 vs. beta 2 receptors of 6- to 39-fold, depending on the method employed to assess subtype potency. In addition, carvedilol was also a potent alpha 1-blocking agent, with a beta 1:alpha 1 blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2-receptors and in human myocardial membranes containing both beta 1- and beta 2-receptors carvedilol exhibited the unique property of guanine nucleotide modulatable binding. Despite this, no intrinsic sympathomimetic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes. Vasodilation related to alpha 1-blockade and the lack of intrinsic activity should translate into improved tolerability and good efficacy in the treatment of heart failure.
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PMID:Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes. 135 Apr 78

Circulating plasma concentrations of norepinephrine, renin, angiotensin and vasopressin are increased in congestive heart failure. By increasing ventricular afterload, heart failure is further worsened, which in turn--in a vicious cycle--stimulates neurohumoral vasoconstrictor mechanisms. Furthermore, because of the compensatory but excessive stimulation of the sympathomimetic system, a down-regulation and desensitization particularly of the myocardial beta 1 receptors and depletion of myocardial catecholamine occurs in chronic heart failure. These defects may be restored toward normal by interventions that attenuate the activity of the sympathetic nervous system. A direct approach to modify the excessive vasoconstriction is to administer systemic vasodilator drugs, but despite favorable short-term effects, tolerance developed to most of these drugs during long-term treatment. One reason for the loss of effectiveness is the reflex activation of the sympathetic system, which increases vasoconstrictor hormone concentrations. Activation of the renin-angiotensin system can be modified effectively by angiotensin-converting enzyme inhibitors that have shown favorable responses in patients with chronic heart failure. Beta-blocking agents interfere with endogenous sympathetic activation and have produced beneficial effects in patients with congestive cardiomyopathy. Long-term treatment is associated with up-regulation of the number of beta receptors and an improved responsiveness to catecholamines. Owing to the negative inotropic effects of beta-blocking agents, some of the patients with severe heart failure deteriorated hemodynamically and clinically. Theoretically, it should be advantageous to have a substance that combines protection against excessive beta stimulation with a mild inotropic support to prevent cardiac decompensation. This may be achieved by a selective beta 1-partial agonist like xamoterol.
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PMID:Interrupting the adaptive changes in congestive heart failure. 167 86

Ibopamine is an orally active derivative of dopamine (DA) which metabolizes to its active form, epinine. Epinine is one of the few catecholamines that possess dopaminergic--DA1 and DA2--activity, alpha 1, alpha 2, beta 1, and beta 2 activity, with indirect sympathomimetic action of dopamine. Ibopamine increased positive dP/dt, stroke volume, aortic blood flow, renal blood flow, and diuresis in animals. In healthy volunteers and patients with heart failure, a single oral dose of ibopamine showed primary vasodilating action (postsynaptic DA1 activity and presynaptic DA2 activity). Following a single oral dose of 100 or 200 mg of ibopamine, the plasma concentration of epinine reached its peak within 30 minutes, and declined rapidly so that concentration was not detectable after 1.5-3 hours. Pharmacokinetics and hemodynamic effects in congestive heart failure patients are also discussed.
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PMID:Clinical pharmacology of ibopamine. 167 50

The efficacy of enoximone (EN), a new phosphodiesterase inhibitor, was studied in 24 patients (pts.) with end-stage cardiac disease due to dilative cardiomyopathy (21 pts.) or coronary heart disease (3 pts.). All pts. admitted for urgent transplantation or mechanical circulatory support demonstrated advanced cardiac failure unresponsive to conventional pharmacotherapy. Despite maximal catecholamine and vasodilator therapy the cardiac index averaged 2.08 l/min per m2, the pulmonary capillary wedge pressure (PCWP) 24 mmHg, and the systemic vascular resistance (SVR) 1450 dyn* s* cm-5. In addition to the previous sympathomimetic medication EN was administered as a bolus injection of 1 mg/kg followed by a continuous infusion of 4 to 10 micrograms/kg/min. In all but 4 non-responding pts., who eventually died, clinical and hemodynamic conditions improved significantly within 4 h: CI increased from 2.08 to 3.1 l/min/m2, PCWP dropped from 24 to 17 mmHg, and SVR decreased from 1450 to 950 dyn* s* cm-5 (all p less than 0.05). After initial improvement, 9 pts. experienced acute hemodynamic and clinical deterioration leading to implantation of a biventricular-assist device (Berlin Heart) in 6 pts., while 3 pts. died of irreversible cardiogenic shock. However, of the remaining 15 pts., who demonstrated sustained hemodynamic improvement, 11 could be weaned off their adrenergic medication and remained on oral EN (1.0 to 1.5 mg/kg TID). Three pts. received heart transplants within 8 to 12 weeks; 7 pts. were still on the waiting list at the end of the study, and 1 pt. died after withdrawal of oral EN.2
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PMID:[Enoximone as pharmacologic "bridging" to heart transplantation]. 183 94

More and more patients with coronary heart disease (CAD) are admitted to intensive care units. The drugs used to treat these patients have various effects on the myocardium which must be known in order to avoid worsening the CAD. This review examines the metabolic effects on the myocardium of the most commonly used drugs in intensive care. The physiology of myocardial oxygen supply is first recalled with regard to the coronary circulation, myocardial oxygen extraction and consumption. Digitalis glycosides do not affect the coronary circulation, but the decrease myocardial oxygen consumption in patients with heart failure, mainly by lowering heart rate. Dihydropyridine calcium blockers (nifedipine, nicardipine) increase coronary blood flow, despite a decrease in arterial blood pressure. Their effects on myocardial oxygen consumption are mediated by a sympathetic reflex. Verapamil decreases the heart rate and myocardial inotropism, and is responsible for coronary vasodilation. The result is a decrease in myocardial oxygen consumption. Diltiazem and bepridil have almost similar effects: they decrease myocardial oxygen consumption and increase blood supply to the heart. It has been recently shown that verapamil was the most depressant calcium channel blocking agent, and that it resulted in the most important decrease in myocardial metabolism. Beta-blocking agents decrease myocardial metabolism, except those with an important intrinsic sympathomimetic activity, such as pindolol. Amiodarone can be considered as an alpha and beta blocking drug: its main effect is to counteract the effects of endogenous catecholamines on myocardial metabolism. The sympathomimetic amines (noradrenaline, adrenaline, isoprenaline, dopamine, dobutamine) increase, to different extents, myocardial oxygen consumption. Vasodilators, such as the nitrates or sodium nitroprusside, decrease cardiac filling pressures, and increase myocardial blood flow, thus lowering myocardial oxygen consumption. Phosphodiesterase inhibitors (amrinone, enoximone) have both an inotropic and a vasodilating effect. They decrease cardiac afterload, and increase blood supply to the myocardium; this compensates for the increase in myocardial oxygen consumption due to the increase in myocardial contractility. Because all the drugs used in intensive care have different effects on myocardial metabolism, their reasoned use should avoid an inappropriate increase in oxygen demand.
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PMID:[Changes in myocardial metabolism induced by drugs used during intensive care]. 197 Apr 63

The purpose of the present study was to characterize the effects of xamoterol in the human myocardium. In the presence of forskolin or milrinone, xamoterol increased isometric force of contraction, contraction velocity, and relaxation velocity in isolated, electrically driven preparations from human myocardium, but had no effect alone. There was no difference in the effect of xamoterol between right atrial myocardium and left ventricular myocardium from nonfailing (NF), moderately failing (NYHA II-III), and severely failing (NYHA IV) human hearts. The positive inotropic and lusitropic effects of isoprenaline were reduced depending on the severity of heart failure in left ventricular myocardium (i.e., NF greater than NYHA II-III greater than NYHA IV). In the presence of norepinephrine, xamoterol produced negative inotropic effects similar to those of the beta-adrenoceptor antagonists pindolol and propranolol. Xamoterol alone had no effects on force of contraction, whereas pindolol and propranolol markedly reduced contractile force. In NYHA class IV, isoprenaline stimulated adenylate cyclase about twofold but xamoterol, like pindolol or propranolol, had no effect. Experiments with the beta 1- and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, showed that the positive inotropic and lusitropic effects of xamoterol were mediated by beta 1-adrenoceptors. Consistently, xamoterol had a selectivity of 13.8 at beta 1-adrenoceptors as measured in radioligand binding experiments. It is concluded that xamoterol acts as a beta 1-adrenoceptor antagonist with a selectivity of 13.8 in human ventricular myocardium. The compound has an intrinsic sympathomimetic activity, as it produces beta 1-adrenoceptor-mediated positive inotropic and lusitropic effects in the presence of forskolin. The beneficial effects of xamoterol in patients with heart failure could be due to prevention of the detrimental effects of norepinephrine such as beta 1-adrenoceptor downregulation of an increase of Gi (inhibitory guanine-nucleotide binding protein).
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PMID:Effects of xamoterol on inotropic and lusitropic properties of the human myocardium and on adenylate cyclase activity. 197 79

Cardiac transplantation is theoretically the optimal final treatment of terminal cardiac failure but the indications, especially in the emergency situation, should be carefully considered. Sympathomimetic agents are of limited use in patients with severe cardiac failure partly because of the down regulation of the myocardial beta-receptors. The phosphodiesterase inhibitors, represented by enoximone, are valuable because of their action on the cardiac muscle (inotropic and lusitropic) and their direct systemic vasodilator effect. Enoximone can be administered by intravenous bolus resulting in a rapid onset of action (peak at 30 minutes) with a prolonged effect due to its hepatic metabolites. The authors' experience in this indication dates over 5 years and over 50 patients were included. A preliminary study in 34 patients with cardiac failure resistant to betamimetic drugs, referred to the intensive care unit for urgent cardiac transplantation, or, in the absence of a donor, circulatory assistance is reported. A Swan Ganz catheter and radial artery canula were inserted for haemodynamic monitoring and enoximone was administered in an intravenous bolus over 15 minutes every 8 hours in addition to sympathomimetic agents. A haemodynamic improvement was observed after the 30th minute in 30 patients. The cardiac index increased from 1.82 to 2.67 l/mn/m2 and the pulmonary capillary pressures decreased from 30.8 to 18.9 mmHg. Systemic arterial resistances fell from 2,170 to 1,520 dynes.s.cm-5. No haemodynamic improvement was observed in 4 patients who were treated by mechanical ventricular assistance. After investigations to detect contra-indications to cardiac transplantation, 12 of the 30 patients remained candidates for cardiac transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Medical strategy in patients awaiting emergency heart transplantation]. 214 25

Enoximone belongs to a new class of noncatecholamine-positive inotropes, which selectively inhibit phosphodiesterase type III and increase cyclic AMP (cAMP). This study was performed in 30 coronary artery surgery patients with impaired myocardial function (ejection fraction [EF] less than 50%). The study's two purposes were to investigate the hemodynamic effects of enoximone, 0.5 mg/kg, administered following induction of anesthesia (phase I), and to assess whether enoximone can potentiate the actions of sympathomimetic agents during weaning from cardiopulmonary bypass (CPB) (phase II). Starting with already reduced hemodynamics, induction of anesthesia led to a further deterioration of blood pressure and cardiac output (CO). Administration of enoximone produced a significant increase in cardiac index (CI) (+47%), whereas pulmonary capillary wedge pressure (PCWP) (-37%), pulmonary artery pressure (PAP) (-17%), and systemic vascular resistance (SVR) (-17%) were significantly reduced. Heart rate (HR) was not increased, and no dysrhythmias occurred during the investigation. The hemodynamic effects were maintained for 30 minutes until the start of the operation. In phase II, where weaning from CPB was not possible without pharmacological support, either enoximone (0.5 mg/kg) + epinephrine (0.1 micrograms/kg/min) or only epinephrine (same dosage) was randomly selected. Weaning was successful in both groups, but the combined therapy produced a larger increase in cl and a more pronounced decrease of the elevated filling pressure (PCWP). PAP was not changed in the combined therapy group, but increased in the patients receiving epinephrine alone. It is concluded that enoximone has beneficial hemodynamic effects in the perioperative period, and that potentiation of the effects of epinephrine in severe heart failure may be one of the drug's most useful features.
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PMID:Enoximone treatment of impaired myocardial function during cardiac surgery: combined effects with epinephrine. 215 89

MCI-154 is a potent nonglycoside and non-sympathomimetic cardiotonic agent with a pyridazinone structure. We assessed its cardiac and coronary vasodilator effects by use of isolated, blood-perfused papillary muscle, sinoatrial (SA) node, and atrioventricular (AV) node preparations of dogs. The drug (1-100 nmol) was injected intraarterially. MCI-154 increased the force of contraction of paced and unpaced papillary muscles but failed to affect the rate of automaticity of the latter. It increased sinus rate and shortened AV conduction time by accelerating AV nodal conduction, but in all doses examined it produced no arrhythmias. In all preparations, it increased blood flow. All the effects were long-lasting (1-2 h). MCI-154, however, was not homogeneously effective on these cardiovascular variables. The drug was nearly equieffective in producing a positive inotropic effect and coronary vasodilatation, but less effective in producing positive chronotropic and dromotropic effects. In having such a cardiovascular profile, MCI-154 most resembles milrinone among new cardiotonic agents, although unlike milrinone, its main mechanism of cardiotonic action is believed to be the sensitization of the contractile proteins to Ca2+. Whatever mechanisms are involved, the revealed cardiovascular profile of MCI-154 justifies its clinical trial in the treatment of heart failure.
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PMID:Cardiac and coronary vasodilator effects of the novel cardiotonic agent, MCI-154, assessed in isolated, blood-perfused dog heart preparations. 245 Feb 40


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