Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Milrinone is a promising new inotrope, but its arrhythmogenic potential has not been defined. We monitored ventricular arrhythmias during a 24-hour baseline and 48-hour milrinone infusion period in 12 patients with chronic heart failure. Patients were characterized by a mean age of 58 years and a left ventricular ejection fraction of 21%. Nine (75%) were male, nine had primary idiopathic dilated cardiomyopathy, and three had coronary artery disease. None had a history of cardiac arrest or sustained ventricular tachyarrhythmia. Milrinone was given as a loading dose (mean 53 micrograms/kg/10 min; range 37.5 to 75) followed by a 48-hour maintenance infusion (mean 0.53 micrograms/kg/min; range 0.25 to 0.75). Acutely, cardiac index increased by 27% and pulmonary wedge pressure decreased by 30% during milrinone; changes were maintained during continued therapy. Ventricular arrhythmia response was variable, with no significant overall difference. However, a trend toward increased ectopic activity was noted. No sustained tachyarrhythmias occurred. Mean frequency of premature ventricular complexes (PVCs) was 87 +/- 48 PVCs/hr (x +/- SEM) during baseline monitoring and 141 +/- 69/hr following infusion of the drug (p = 0.08). Mean frequency of couplets was 6.0 +/- 4.9/hr before drug infusion and 14.3 +/- 11.0/hr during infusion (p = 0.21). Mean frequency of runs was 0.9 +/- 0.8/hr before and 2.7 +/- 2.4/hr during drug infusion (p = 0.29). Two patients met criteria for proarrhythmia (increased PVCs of greater than 4x and/or repetitive forms of greater than 10x. However, neither proarrhythmia patient required reduction in the dosage of milrinone or additional antiarrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Occurrence of ventricular arrhythmias in patients receiving acute and chronic infusions of milrinone. 395 54

Milrinone is a new bipyridine-positive inotropic agent that is closely related to amrinone. In the nonfailing heart, coronary blood flow was increased and coronary bed resistance was decreased by milrinone, most probably by a direct action of milrinone on the coronary vasculature. Oxygen consumption was increased at the lower workloads. In the failing heart milrinone (0.1 to 0.5 mg/L of blood) increased cardiac output and coronary blood flow and reduced coronary vascular resistance. With the 0.1 mg dose oxygen consumption was reduced, especially at the high workloads, and was not significantly changed at the low work levels. With higher doses of milrinone oxygen consumption of the heart was not changed significantly while external work was increased. These data show that milrinone can increase the work of the heart with a decrease or no significant change in oxygen consumption of the isolated failing heart. The use of this drug in heart failure accompanied by restricted blood flow may thus be indicated.
 ...
PMID:The effects of milrinone (Win 47203) on the coronary blood flow and oxygen consumption of the dog heart-lung preparation. 395 93

Milrinone is a potent positive inotropic and vascular smooth muscle-relaxing agent in vitro, and therefore, it is not known to what extent each of these actions contributes to the drug's hemodynamic effects in patients with heart failure. In 11 patients with New York Heart Association class III or IV congestive heart failure, incremental intravenous doses of milrinone were administered to determine the dose-response relationships for heart rate, systemic vascular resistance, and inotropic state, the latter measured by peak positive left ventricular derivative of pressure with respect to time (dP/dt). To clarify further the role of a positive inotropic action, the relative effects of milrinone and nitroprusside on left ventricular stroke work and dP/dt were compared in each patient at doses matched to cause equivalent reductions in mean arterial pressure or systemic vascular resistance, indices of left ventricular afterload. Milrinone caused heart rate, stroke volume, and dP/dt to increase, and systemic vascular resistance to decrease in a concentration-related manner. At the two lowest milrinone doses resulting in serum concentrations of 63 +/- 4 and 156 +/- 5 ng/ml, respectively, milrinone caused significant increases in stroke volume and dP/dt, but no changes in systemic vascular resistance or heart rate. At the maximum milrinone dose administered (mean serum concentration, 427 +/- 11 ng/ml), heart rate increased from 92 +/- 4 to 99 +/- 4 bpm (P less than 0.01), mean aortic pressure fell from 82 +/- 3 to 71 +/- 3 mmHg (P less than 0.01), right atrial pressure fell from 15 +/- 2 to 7 +/- 1 mmHg (P less than 0.005), left ventricular end-diastolic pressure fell from 26 +/- 3 to 18 +/- 3 (P less than 0.005), stroke volume index increased from 20 +/- 2 to 30 +/- 2 ml/m2 (P less than 0.005), stroke work index increased from 14 +/- 2 to 21 +/- 2 g X m/m2 (P less than 0.01), and dP/dt increased from 858 +/- 54 to 1,130 +/- 108 mmHg/s (P less than 0.005). When compared with nitroprusside for a matched reduction in mean aortic pressure or systemic vascular resistance, milrinone caused a significantly greater increase in stroke work index at the same or lower left ventricular end-diastolic pressure. Milrinone caused a concentration-related increase in dP/dt (32% increase at maximum milrinone dose), whereas nitroprusside had no effect. These data in patients with severe heart failure indicate that in addition to a vasodilating effect, milrinone exerts a concentration-related positive inotropic action that contributes significantly to the drug's overall hemodynamic effects. The positive inotropic action occurs at drug levels that do not exert significant chronotropic or vasodilator effects.
 ...
PMID:Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. 397 22

Milrinone is a recently synthesized bypyridine compound with positive inotropic and arteriolar dilating properties in persons and experimental animals. To examine the efficacy and safety of milrinone to treat myocardial failure in dogs, dogs with myocardial failure were selected from the patient populations of 3 veterinary hospitals. Progressively increased dosages of milrinone, from 0.05 to 1.0 mg/kg of body weight, were administered over 14 days, and cardiac responses, as determined by M-mode echocardiography, and clinical responses were recorded. An effective dosage of milrinone was identified for each dog and administered for 4 weeks to evaluate the stability of the cardiac response. A randomized blinded study of drug vs nondrug capsule or nondrug elixer (designated placebo) was performed at the end of 4 weeks to eliminate possible effects of investigator bias or spontaneous regression of the disease. The duration of drug effect was determined by evaluating echocardiographic measurements of left ventricular function for 12 hours after drug administration. Echocardiographic evaluation of left ventricular function improved in dogs given milrinone. The effective dosage was between 0.5 and 1.0 mg/kg. Tolerance to milrinone did not develop during the 4-week study. In dogs given placebo during the randomized blinded study, echocardiographic values decreased significantly. Dogs that were given milrinone remained echocardiographically stable. During the study, 6 dogs improved clinically, 5 remained the same, 1 had a decrease in exercise tolerance, 1 died of severe heart failure, and 1 died of hypoadrenocorticism. Ventricular tachydysrhythmia was exacerbated in 2 dogs, but was not treated.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Echocardiographic and clinical effects of milrinone in dogs with myocardial failure. 403 92

Milrinone is a potent non-catecholamine, non-glycoside inotropic agent that can improve hemodynamic performance and functional capacity in patients with severe congestive heart failure. However, the potential effect of chronic inotropic stimulation on ventricular arrhythmias in patients with heart failure requires evaluation. We compared 24-hour ambulatory ECGs before and 2 to 4 weeks after initiation of chronic milrinone therapy in 20 patients with severe congestive heart failure (mean cardiac index 1.79 +/- 0.43 L/min/m2). A greater than tenfold increase in simple ventricular premature complex (VPC) density, a greater than tenfold increase in complex VPC form density, or an increase from 0 to greater than 5 episodes per 24 hours of any complex VPC form occurred in 35% (7 of 20) of patients. A greater than tenfold reduction in simple VPC density was noted in 5% (1 of 20), while 60% (12 of 20) of the study group had no significant change in ventricular arrhythmia profile on milrinone. The hemodynamic and functional response to milrinone, as well as entry hemodynamic profiles, were unrelated to the change in frequency or complexity of ventricular arrhythmias during therapy. Thus, milrinone therapy in congestive heart failure may be associated with the development of VPC complexity and with a significantly increased density of complex VPC forms.
 ...
PMID:Milrinone in congestive heart failure: observations on ambulatory ventricular arrhythmias. 405 Jun 52

Milrinone (Win 47203) is a potent cardiac bipyridine with inotropic and vasodilator properties. Its effects were studied in anesthetized and unanesthetized dogs and in isolated cardiac tissues from guinea pigs. In the anesthetized dog, the intravenous injection of milrinone (0.01-0.1 mg/kg) increased cardiac contractile force (CF) (23 +/- 6.1 to 87 +/- 8.9%), maximum left ventricular pressure development (24 +/- 5.8 to 119 +/- 16.1%), and cardiac output (16 +/- 4.5 to 33 +/- 8.9%), with less than a 30% increase in heart rate (HR). Significant decreases in systolic and diastolic blood pressures were seen at 0.3-3 mg/kg i.v. Oral doses of milrinone (0.1-1.0 mg/kg), in unanesthetized dogs, increased cardiac CF by 35 +/- 7.0 to 99 +/- 17.0%, with a maximum increase in HR of 40 +/- 7.1% and no significant change in blood pressure. Milrinone was effective in the presence of ouabain and dopamine without enhancing their arrhythmogenic properties. It was also effective in reversing propranolol-, verapamil-, or pentobarbital-induced heart failure. The inotropic response does not seem to involve the stimulation of the autonomic receptors, the release of endogenous catecholamines, histamine, or prostaglandins, or the inhibition of Na+,K+-adenosine triphosphatase. Milrinone is an inhibitor or cardiac adenosine 3',5'-monophosphate (cAMP) phosphodiesterase, with resultant increases in cardiac cAMP levels. However, the time course for this increase does not seem to correspond to the increase in muscle developed tension, and, therefore, it is unlikely to be responsible for the initiation of the inotropic response. Milrinone is a potent cardioactive agent which should be beneficial in the treatment of acute and chronic congestive heart failure.
 ...
PMID:Cardiotonic activity of milrinone, a new and potent cardiac bipyridine, on the normal and failing heart of experimental animals. 619 67

Milrinone (Win 47203) is a dipyridine related to amrinone, which is about 20-50 times as effective as amrinone when assayed on cardiac contractility. In dog heart-lung preparations, milrinone in a concentration of 0.25-0.5 microM produced a near maximal positive inotropic effect on a variety of acute heart failures. This dosage produced a minimal increase in heart rate and reduced the PR interval. Large doses of milrinone did not produce cardiac irregularities and in Nifedipine heart failure with ventricular irregularities, it eliminated these irregularities. Papaverine-induced heart failure was resistant to ouabain, epinephrine and milrinone therapy. In the presence of positive inotropic amounts of papaverine or theophylline, a pentobarbital heart failure was superimposed. This heart failure responded poorly to milrinone, although it responded to both the addition of epinephrine and ouabain. It is thus possible that milrinone, papaverine and theophylline have closely related sites of action.
 ...
PMID:The search for a digitalis substitute II milrinone (Win 47203). Its action on the heart-lung preparation of the dog. 664 77

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.
 ...
PMID:Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure. 688 53

We wished to provide comparative information regarding the direct effects of flosequinan, a novel quinolone under development for treating heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--milrinone, ouabain, captopril and diltiazem--that have been used to treat heart failure patients, as well as for flosequinoxan, which is the primary metabolite of flosequinan. Flosequinan produced a potent and balanced relaxant effect on norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations, flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with flosequinan and flosequinoxan in the following ways: Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations; ouabain produced both vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of flosequinan and flosequinoxan is unique as compared with that of other agents that have been used to treat patients with heart failure.
 ...
PMID:Assessment of flosequinan's direct effect on human arterial, venous, and cardiac muscle: comparison with other classes of agents used to treat heart failure. 752 63

The present study evaluated the acute hemodynamic response, effects on subjective symptoms and physical findings, and the pharmacokinetics of a single oral dose (2.5, 5, or 10 mg) of milrinone in 31 patients with acute or decompensated heart failure. We found a significant increase in cardiac index (29, 31, and 29%, respectively, p < 0.01) and a significant decrease in pulmonary capillary wedge pressure (39, 43, and 47%, respectively, p < 0.01) accompanied with improvement in subjective symptoms and physical findings. These hemodynamic effects persisted for 4-8 h after each dosage of milrinone. Dose-dependent hemodynamic response was observed between the drug concentration and percent maximum changes in pulmonary capillary wedge pressure (peak milrinone concentration, 2.5 mg: 99.99 +/- 57.49, 5 mg: 187.11 +/- 71.37, and 10 mg: 300.94 +/- 158.5 ng/ml). The finding, together with results of the Prospective Randomized Milrinone Survival Evaluation (PROMISE) study, suggests lower dose of milrinone will be useful for the short-term inodilator support in patients with acute or decompensated heart failure.
 ...
PMID:Hemodynamic effects and pharmacokinetics of oral milrinone for short-term support in acute heart failure. 772 86


<< Previous 1 2 3 4 5 6 7 8 Next >>