Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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

The efficacy of orally active 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) as a positive inotropic agent was examined using model right-sided heart failure dogs and compared with those of dobutamine and amrinone. Heart failure was produced in beagle dogs by a combination of tricuspid insufficiency and pulmonary stenosis, and then drugs were administered intravenously or orally. Intravenous OPC -8212, 1 and 3 mg/kg, amrinone, 1 and 3 mg/kg, and dobutamine, 0.01 and 0.03 mg/kg, increased the dP/dt of the right ventricular pressure for 5 to 10 min. These positive inotropic effects were accompanied by simultaneous increase in the heart rate in the cases of amrinone and dobutamine, and was accompanied by hypotension in the case of amrinone. However, OPC -8212 did not show such effects. This indicates that OPC -8212 has a relatively selective positive effect on cardiac contractility. Oral administration of OPC -8212, 10 to 100 mg/kg, and amrinone, 10 and 30 mg/kg, also showed a positive inotropic effect, appearing 1 h after administration and lasting up to the 5th h. Amrinone had about a 3 times stronger effect, but for similar positive inotropic effects, only amrinone showed positive chronotropic effect. The hypotensive effect of amrinone was also observed after oral administration, while such an effect was scarcely observed when using OPC -8212.
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PMID:Positive inotropic effect of 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212) in the dog with experimentally-induced right-sided heart failure. 654 94

The effects of amrinone on human umbilical artery and human myocardium were studied. Amrinone produced dose related increases in tension, dT/dtmax and dT/dtmin in myocardium from patients who were NYHA grade I (n = 1) and II (n = 4). The responses to amrinone of these tissues were similar to the response seen in normal guinea-pig myocardium (n = 34). The drug had no inotropic effect on tissue from NYHA grade III patients (n = 5). The inotropic response of the tissues to amrinone was inversely related to length of history and severity of heart failure in the patients from whom the tissues were obtained. Amrinone caused dose related relaxation of the human umbilical artery. The vasodilator properties, but not the positive inotropic effects of amrinone were detectable at concentrations of the drug obtained during oral therapy (0.4 to 4.0 micrograms X ml-1). These findings support the view that in patients with congestive cardiac failure amrinone acts by vasodilatation with no clinically important positive inotropic effect.
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PMID:Inotropic and vasodilator effects of amrinone on isolated human tissue. 673 34

A patient with severe cardiac failure due to idiopathic congestive cardiomyopathy resistant to conventional therapy, responded to amrinone, a new non-glycosidic non-catecholamine positive inotropic agent. Amrinone produced significant haemodynamic improvement during both intravenous and oral administration. Thrombocytopaenia, however, was induced, necessitating cessation of the drug. Amrinone is a promising, orally effective inotropic agent for patients with refractory congestive cardiac failure, but is limited to its tendency to cause thrombocytopaenia.
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PMID:Amrinone--a new inotropic agent in chronic resistant congestive cardiac failure. 694 45

Heart failure is a syndrome with distinct clinical signs and symptoms. The severity of cardiac failure and a deterioration in functional capacity can be determined by a progressive exercise test and by the noninvasive determination of maximum oxygen uptake. In patients with severe cardiac failure refractory to medica therapy, particularly those with cardiomyopathy or ischemic heart disease, survival is seriously compromised, resembling the most serious malignancy. Cardiotonic agents may be useful in improving the quality of life, provided that they are effective and are given sufficiently early in the course of the disease. Dobutamine given intravenously augments cardiac performance and improves renal function in patients with very advanced disease refractory to multiple diuretics; long-term survival, however, remains dismal. Amrinone appears to be a promising agent for the long-term treatment of chronic cardiac failure; the utility of pirbuterol, an oral catecholamine analog, remains to be determined.
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PMID:Cardiotonic agents in the management of chronic cardiac failure. 706 6

Amrinone has been shown to exhibit a potent inotropic effect in patients with heart failure secondary to congestive cardiomyopathy, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) are unknown. Accordingly, the hemodynamic, myocardial metabolic and ECG responses to amrinone (2.5 mg/kg i.v. over 1 hour) were measured in nine patients with congestive heart failure secondary to coronary artery disease. Increases were observed in cardiac index (1.3 +/- 0.4 to 2.2 +/- 0.7 l/min/m2) and left ventricular stroke work (10.6 +/- 3.0 to 19.2 +/- 6.3 g-m/m2), and decreases in mean pulmonary wedge (31 +/- 5 to 26 +/- 4 mm Hg), mean pulmonary artery (44 +/- 8 to 36 +/- 7 mm Hg) and mean right atrial pressures (18 +/- 4 to 10 +/- 4 mm Hg), myocardial arteriovenous oxygen difference (129 +/- 19 to 109 +/- 17 ml/l), CBF (215 +/- 117 to 178 +/- 84 ml/min) and MVO2 (27 +/- 14 to 19 +/- 9 ml/min). All changes were significant (p less than 0.01). No significant changes occurred in aortic mean pressure, heart rate, myocardial lactate extraction or ECG, and no patient developed angina. In explaining the decline in MVO2, it is possible that the increase in contractility was more than offset by the reductions in preload and afterload. The amrinone-induced hemodynamic improvement in patients with congestive heart failure secondary to coronary artery disease was associated with reductions in MVO2 and CBF and no evidence of myocardial ischemia.
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PMID:Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease. 737 83

The present study compared the effects of amrinone, dobutamine, dibutyryl cAMP, digoxin, and isoproterenol on mechanical performance, the high energy phosphate metabolites, and the [Ca2+]i transients in normal and cardiomyopathic hamster hearts with severe heart failure. In normal hearts dobutamine, dibutyryl cAMP, and isoproterenol increased left ventricular developed pressure, while amrinone and digoxin did not. However, the amplitude of [Ca2+]i transients was augmented with all drugs. Diastolic [Ca2+]i level was increased with dobutamine and lowered with dibutyryl cAMP and isoproterenol. In cardiomyopathic hearts with severe heart failure, left ventricular developed pressure, the amplitude of [Ca2+]i transients, the phosphorylation potential, and [cAMP]i were significantly depressed and left ventricular end-diastolic pressure and diastolic [Ca2+]i were significantly elevated when compared with normal hearts. Amrinone, dibutyryl cAMP, and isoproterenol improved mechanical performance while increasing [cAMP]i and the amplitude of [Ca2+]i transients, and decreasing diastolic [Ca2+]i. On the other hand, with dobutamine and digoxin diastolic [Ca2+]i was further increased and mechanical performance deteriorated with digoxin. Thus, distinct differences exist in modulation of mechanical performance, high-energy phosphate metabolism, and [Ca2+]i transients by positive inotropic drugs between normal and cardiomyopathic hearts with severe heart failure.
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PMID:Distinct modulation of myocardial performance, energy metabolism, and [Ca2+]i transients by positive inotropic drugs in normal and severely failing hamster hearts. 778 36

Amrinone is a noncatecholamine inotropic agent used clinically in the management of heart failure. The purpose of this study was to determine if intravenous (i.v.) infusion of amrinone has beneficial effects during resuscitation from experimental hemorrhagic shock. Effectiveness was defined as significantly improved survival rate. Mean arterial pressure (MAP) and tissue oxygen tension (pO2) were measured to assess the physiologic effects of amrinone. Two separate randomized and blinded survival trials were conducted. In each trial, rats were randomly assigned to either a control group (n = 10) or an experimental group (n = 10). All animals were bled 27 ml/kg over 2 minutes and maintained in shock for 45 minutes before resuscitation. Resuscitation in placebo (control) animals was with 54 ml/kg (2 times the hemorrhage volume) Lactated Ringer's solution over 1 hour, whereas resuscitation in drug-treated animals was with a 0.75 mg/kg bolus amrinone over 3 minutes followed by 54 ml/kg Lactated Ringer's solution and 5 ug/kg/min infusion over 1 hour. Results were that resuscitation with amrinone significantly increased MAP, tissue pO2, and survival over resuscitation with Lactated Ringer's alone (P < 0.05). In both trials, survival rates increased by more than 66 per cent in the amrinone groups.
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PMID:Amrinone improves survival in hemorrhagic shock. 794 32

A crucial element for weaning patients from cardiopulmonary bypass (CPB) rests on the selection of an appropriate therapeutic regimen. Amrinone, a phosphodiesterase III inhibitor, combines inotropic support with pulmonary and systemic vasodilatation, without increasing heart rate (HR) or myocardial oxygen consumption. These characteristics should be useful in the failing heart during weaning from CPB. Nineteen patients were included in this prospective, open-labelled, phase IV study when systolic blood pressure (DPAP) > 15 mmHg or central venous pressure (CVP) > 15 mmHg, during progressive separation from CPB. At that moment, CPB flow was increased to alleviate heart failure and amrinone administered as a bolus (0.75 mg.kg-1) followed by an infusion (10 micrograms.kg-1.min-1). Weaning from CPB was then resumed and haemodynamic variables (SBP, DPAP, CVP and HR) were compared with those measured at CPB flow when failure had first occurred. Failure to wean from CPB occurred at 57 +/- 28% of full pump flow. After the amrinone bolus, DPAP and CVP decreased by 20% and 21% respectively. Subsequently, 16 patients required the infusion of norepinephrine (4-8 micrograms.min-1) to maintain a SBP > 80 mmHg. Heart rate remained unchanged after the bolus of amrinone, after separation from CPB, and no arrhythmias were noted. Successful weaning from CPB was possible 12 +/- 8 min after the amrinone bolus. Weaning resulted in a cardiac index similar to that measured pre-bypass. Amrinone is rapidly effective during weaning from CPB and, in combination with norepinephrine, provides the necessary inotropic support during this unstable period.
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PMID:Amrinone, in combination with norepinephrine, is an effective first-line drug for difficult separation from cardiopulmonary bypass. 840 12

Induction of ventricular fibrillation (VF) is an important part of the process of inserting implantable cardioverter defibrillators (ICDs), allowing the measurement of defibrillation thresholds. However, animal studies have revealed that repeated cycles of VF and defibrillation result in depressed left ventricular (LV) function and reduced cardiac output. Short intervals of VF do not affect myocardial contractility but longer periods produce heart failure. Induced VF was used in a canine model to study profound myocardial stunning leading to heart failure, as well as the therapeutic potential of the phosphodiesterase inhibitor, amrinone (combined with epinephrine and norepinephrine). Amrinone was found to significantly (p < 0.05) increase contractility when added to a stable preparation supported by epinephrine and norepinephrine infusion; amrinone or catecholamines alone had no effect. In the clinical setting, the following factors may affect LV contractility during ICD surgery: catecholamines released as a result of hypotension; negative VF; ischemia; antiarrhythmic drugs; anesthetics; and bradycardia after device testing. Patients (n = 125) have tolerated ICD insertion well. Early data reveals no significant changes in ejection fraction. Though rare, death due to myocardial stunning and LV power failure can occur during ICD insertion. It may be possible to use arterial pressure monitoring to predict this event in vulnerable patients.
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PMID:Does ventricular fibrillation cause myocardial stunning during defibrillator implantation? 846 13

The inotropic and vasodilating effects of amrinone can upset the balance of O2 supply and demand by changing those components in opposite directions simultaneously. We used a canine model of acute coronary artery occlusion to test our hypothesis that early administration of amrinone (before failure of the heart) would have beneficial effects on hemodynamic status and regional metabolism during ischemia, even before heart failure. Twenty dogs anesthetized with thiamylal were subjected to 50%, 75%, and 100% occlusion of the left anterior descending coronary artery. Half of the dogs were given a bolus injection of amrinone (0.75 mg/kg) 1-2 min before each occlusion, immediately followed by continuous infusion (10 micrograms.kg-1 x min-1) during occlusion; the other half did not receive amrinone (control). Hemodynamic and metabolic variables were measured in the ischemic area (the left anterior descending coronary artery) and in a nonischemic area (the circumflex vein). Amrinone not only decreased heart rate, left ventricular systolic and end-diastolic pressures, and mean pulmonary arterial pressure during constrictions but also maintained contractility, stroke volume index, and stroke volume index/left ventricular end-diastolic pressure before and during constrictions. Regional myocardial blood flow in ischemic areas decreased with amrinone during constrictions but was still higher than in untreated animals. Regional ischemic and nonischemic metabolic variables (metabolism of intracoronary potassium, CO2, O2, glucose, and lactate) were similar for both groups and changed to the same extent. Amrinone appears to improve left ventricular performance and increase blood flow to ischemic myocardium while not worsening regional metabolic effects during various grades of ischemia in the dog.
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PMID:Early administration of amrinone does not impair regional metabolism of O2 or lactate and, by improving myocardial performance, preserves myocardial blood flow in the ischemic canine heart. 849 55


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