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:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the haemodynamic effects of i.v. milrinone, a new phosphodiesterase inhibitor, in patients with low cardiac output after cardiac surgery. Thirty-five patients with a cardiac index (Cl) less than 2.5 litre min-1 m-2 and a pulmonary capillary wedge pressure (PCWP) greater than 8 mm Hg were given a loading dose of milrinone 50 micrograms kg-1 followed by an infusion at one of three rates: 0.375 micrograms kg-1 min-1, 0.5 micrograms kg-1 min-1 or 0.75 micrograms kg-1 min-1 for 12 h. After 1 h there were increases in Cl (35%) (P less than 0.001), heart rate (13%) (P less than 0.01) and stroke volume index (19%) (P less than 0.005). There were decreases in mean arterial pressure (12%) (P less than 0.01), systemic vascular resistance (35%) (P less than 0.001) and PCWP (24%) (P less than 0.05). Pulmonary vascular resistance was unchanged or reduced and left ventricular stroke work index was unchanged or increased. The haemodynamic improvements were sustained throughout the infusion period. Milrinone was tolerated well: three patients developed tachycardia greater than 125 beat min-1, one patient developed atrial fibrillation and one patient had a short run of atrial bigemini. We conclude that milrinone is a useful agent in the treatment of patients with a reduced cardiac output after cardiac surgery.
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PMID:Clinical and haemodynamic effects of milrinone in the treatment of low cardiac output after cardiac surgery. 175 Dec 73

Milrinone is an inotropic agent of the phosphodiesterase inhibitor family. In common with all molecules of this class it has both positive inotropic and vasodilator effects. The haemodynamic effects of 3 dosages of milrinone were studied in 25 patients with low output states after open heart surgery. The low cardiac output was defined as a cardiac index of less than 2.5/min/m2 and pulmonary capillary pressures greater than 8 mmHg. Milrinone was administered as a bolus of 50 micrograms/kg/min over 10 minutes followed by a continuous infusion for at least 12 hours. Six patients were given 0.375 micrograms/kg/min, six patients 0.5 micrograms/kg/min, and 13 patients 0.75 g/kg/min. A significant increase in cardiac index was observed but without any difference between the 3 groups. The heart rate and stroke volumes were increased. There was a mild reduction in systemic blood pressure with a decrease in systemic arterial resistances which returned to almost normal values. Left and right filling pressures did not decrease significantly from the initial values until the end of the bolus injection. Indirect measurements of myocardial oxygen consumption showed an increase in this parameter. There were no changes in blood gas concentrations. The treatment was stopped in only one patient because of peripheral vasodilation. Two patients developed supraventricular tachycardia of no consequence. Milrinone may therefore be proposed as treatment of first intention of low cardiac output states after open heart surgery. It is associated with a mild vasodilatory effect. Improved myocardial function is observed providing attention is paid to vascular filling. None of the maintenance doses used after the bolus injection was shown to be more effective than the others.
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PMID:[Hemodynamic effects of milrinone in the treatment of cardiac insufficiency after heart surgery with extracorporeal circulation]. 176 24

Hemodynamic measurements were done in 42 patients with congestive heart failure of NYHA classes III and IV after administration of the phosphodiesterase inhibitors amrinone und enoximone. Amrinone decreases mean arterial pressure (-4%), right atrial pressure (-39%), and systemic vascular resistance (-23%), while cardiac index and stroke volume index increase to 27% and 26%, respectively; heart rate is nearly unchanged. Enoximone administration in a dose of 1 mg/kg bw produces an increase in cardiac index of 13%, an increase in heart rate of 12%, and a decrease of systemic vascular resistance of 13%, whereas stroke volume index is unchanged. Enoximone in a dose of 1.5 mg/kg bw increases heart rate (+ 9%), cardiac index (+ 33%), and stroke volume index (+ 21%), and decreases systemic vascular resistance (-26%). The hemodynamic profile of amrinone and enoximone in an equal dose shows only slight differences. Furthermore, phosphodiesterase inhibitors produce an increase of cardiac index (+ 19%) and stroke volume index (+ 17%) in patients with pump failure having already received dopamine and dobutamine.
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PMID:[The hemodynamic profile of amrinone and enoximone in patients with severe heart failure]. 183

Phosphodiesterase inhibitors that are selective for cAMP-specific cardiac and vascular PDE III comprise a new group of agents for the treatment of heart failure, which at present are limited to clinical shortterm intravenous use and research uses only. Although both intravenous amrinone and milrinone are FDA approved, only amrinone is available for general clinical use. Selective phosphodiesterase inhibition produces beneficial actions of positive inotropy and peripheral vasodilation that result from increased cardiac and vascular muscle concentrations of intracellular cAMP and ionic calcium. In addition, a positive lusitropic action (enhancement of cardiac relaxation) has been observed. Neither beta-adrenergic agonist activity nor inhibition of the sodium-potassium ATPase is produced by these agents. The magnitude of hemodynamic improvement generally exceeds that of the cardiac glycosides and is comparable with that of intravenous catecholamines such as dobutamine. The different pharmacodynamic profile of the PDE inhibitors is additive to the effects of cardiac glycosides, complementary and synergistic to the actions of catecholamines, and has been shown to have favorable effects on coronary hemodynamics. As a result there is continued enthusiasm for the short-term intravenous use of amrinone and potentially milrinone in the setting of acute heart failure resulting from systolic dysfunction (after myocardial infarction, open heart surgery, or infectious or toxic myocarditis), heart failure resulting from right ventricular systolic dysfunction, and when patients with severe heart failure await cardiac transplantation. Initiation of treatment with an intravenous bolus followed by a maintenance infusion provides prompt increases in stroke volume and cardiac output and simultaneous reductions in right and left ventricular filling pressures and systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute positive inotropic intervention: the phosphodiesterase inhibitors. 203 20

The myocardial effects of milrinone are mediated through inhibition of myocardial phosphodiesterase III. This inhibition results in accumulation of cyclic adenosine monophosphate and consequently increased calcium influx through voltage-dependent channels. The vascular effects also result from increased cyclic adenosine monophosphate. Direct coronary artery infusion of milrinone causes a concentration-related increase in left ventricular +dP/dt and substantial improvement in pump function as indicated by increased stroke work at lower left ventricular end-diastolic pressures. Subsequent intravenous administration of milrinone produces additional hemodynamic improvement, which is associated with a further reduction in systemic vascular resistance and left and right heart filling pressures. There is also a downward displacement of the left ventricular pressure-volume curve and acceleration of isovolumic relaxation, findings which indicate improved diastolic filling and accelerated isovolumic myocardial relaxation, respectively. The former action may reflect unloading of the right ventricle, whereas the latter may be due to improved calcium reuptake in the myocardium. Myocardial oxygen demand is unaltered because peripheral vasodilatation reduces wall stress and counteracts the increased oxygen requirement necessary to support enhanced contractility. This therapeutic profile differs from that of inotropic agents such as dobutamine and vasodilators such as nitroprusside, and contributes significantly to the usefulness of phosphodiesterase III inhibitors such as milrinone in the short-term management of patients with heart failure.
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PMID:Cardiovascular effects of milrinone. 203 24

The benzimidazol analogue BM14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II-IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM14.478. There was a significant decrease of mean pulmonary artery pressure (28 +/- 11 vs. 23 +/- 11 mmHg; p less than 0.05), mean right atrial pressure (8.6 +/- 5.2 vs. 5.0 +/- 4.7 mmHg; p less than 0.02), and systemic vascular resistance (1651 +/- 484 vs. 1206 +/- 252 dynes.s.cm-5; p less than 0.05) as early as 10 min after injection of BM14.478. Pulmonary vascular resistance also was reduced (128 +/- 86 vs. 61 +/- 39 dynes.s.cm-5, 30 min after injection; p less than 0.02). Simultaneously there was a significant increase of cardiac index (2.3 +/- 0.7 vs. 3.1 +/- 0.8 l.min-1.m-2, 10 min after injection; p less than 0.02), and stroke volume index (28.8 +/- 11.7 vs. 33.9 +/- 8.5 ml.min-1.m-2; 30 min after injection; p less than 0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51 +/- 20 vs. 41 +/- 21 pg/ml; p less than 0.02; 30 min after injection) and atrial natriuretic peptide (229 +/- 283 vs. 121 +/- 168 pg/ml; p less than 0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM14.478. Response of plasma renin activity and plasma vasopressin levels to BM14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short-term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.
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PMID:Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM14.478 in patients with congestive heart failure. 204 89

The content of cyclic nucleotides (cAMP and cGMP), hormones (T3, T4, insulin, protein-bound iodine and thyroid-stimulating hormone) and phosphodiesterase activity were examined in the acute period and over time in blood plasma of patients with ischemic stroke. The parameters under study were found to be interrelated. Also, it has been established that the T4/T3 and cAMP/cGMP ratios and the content of insulin may serve as important biochemical criteria for the gravity of ischemic stroke.
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PMID:[Plasma levels of cyclic nucleotides, phosphodiesterase, thyroid hormones and insulin in patients with ischemic stroke]. 217 82

Low cardiac output in acute heart failure can result in a functional impairment of organs, when tissue hypoxia occurs and cardiogenic shock develops. To restore cardiac output, various forms of therapy can be considered. Fluid replacement is sometimes beneficial in acute situations where oedema can reduce effective plasma volume. Vasodilators are often contra-indicated in shock, when arterial pressure is usually low. Inotropic therapy consists primarily of the administration of adrenergic agents. Dopamine and noradrenaline can be indicated in severe hypotension, to maintain coronary perfusion. Dobutamine is the catecholamine of choice to increase myocardial contractility. However, decreased responsiveness of the myocardial receptors to adrenergic stimulation rapidly becomes an important limitation. Phosphodiesterase inhibitors represent an interesting option to increase contractility, also by increasing cyclic AMP levels in the myocardium. In this respect, the combination of phosphodiesterase inhibitors with adrenergic agents is attractive. The additional vasodilatory properties of these agents can contribute to the increase in cardiac output with limited risk of further reduction in arterial pressure. In 13 patients with cardiogenic shock persisting despite the use of adrenergic agents, the addition of enoximone, 0.5 mg/kg, resulted in significant increases in cardiac index and stroke volume index and a significant decrease in pulmonary artery balloon occlusion pressure without consistent change in mean arterial pressure. In 8 patients, a second infusion of 0.5 g/kg amplified these effects. All but one of these patients survived the episode of cardiogenic shock, and 5 patients were discharged alive. In some cases, even lower doses of enoximone resulted in dramatic increases in cardiac output and oxygen transport in patients already treated with dobutamine with limited success.
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PMID:The role of enoximone in the treatment of cardiogenic shock. 217 30

Milrinone is a phosphodiesterase inhibitor which combines vasodilating effects with inotropic effects. Hemodynamic improvement after acute administration and increased survival with chronic milrinone therapy in rats with heart failure have been reported before, and suggest long-term hemodynamic improvement. However, no detailed hemodynamic studies are available on prolonged milrinone therapy in rats with heart failure. Therefore, the hemodynamic effects of 2 weeks' milrinone therapy were now investigated in conscious rats with heart failure due to myocardial infarction. The effects were compared to hemodynamic changes after acute administration. Acute milrinone increased the baseline cardiac output in infarcted rats by increasing heart rate rather than stroke volume. However, the maximal cardiac output achieved when the heart was stimulated through a volume load was improved due to increased stroke volume as well as increased heart rate. The increase in maximally stimulated cardiac output after acute milrinone was found to be related to infarct size. Two weeks' milrinone therapy in chronically infarcted rats dose dependently restored the hemodynamic changes which were caused by infarction. In contrast to acute administration, two weeks' milrinone restored cardiac function without an increase in heart rate. The effects were achieved at a rate of administration which presumably has no acute inotropic effects. The data indicate that acute milrinone in infarcted rats has vasodilating effects. Positive inotropic effects, possibly masked by concomitant venodilatation at baseline conditions, became overt after stimulation by volume loading. Long-term milrinone dose dependently restored cardiac function in infarcted rats without effects on heart rate or mean arterial pressure, suggesting that different mechanisms may be involved.
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PMID:Beneficial hemodynamic effects of two weeks' milrinone treatment in conscious rats with heart failure. 222 21

The laterofrontal (LF) cirri on isolated gill filaments of Mytilus edulis, prepared in natural seawater, are active and initially beat with an average frequency of about 8 Hz (with a range of 6-14 Hz). However, the lateral (L) cilia on these filaments are arrested in a position at the end of their recovery stroke. Perfusion of the filament with artificial seawater (ASW), with or without 1% ethanol, has little or no biological effect on the activity of the LF cirri, although a transitory decrease in frequency often accompanies the perfusion process. The L cilia remain arrested during perfusion with ASW. The exposure of the gill to low levels of 5-hydroxytryptamine (5HT) (10(-8) less than 5HT less than 10(-7) M) has no effect on the activity of the LF cirri but stimulates the L cilia to beat. Exposure to higher concentrations of 5HT (greater than 10(-7) M) elevates the beat frequency of the L cilia and simultaneously inhibits the activity of the LF cirri, leading to their arrest in a position at the end of the effective stroke. This arrest of the LF cirri occurs as the L cilia attain a 5HT-induced beat frequency between 12 to 14 Hz. The influence of 5HT on the L cilia and the LF cirri can be reversibly mimicked or enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). A concentration of 0.5 mM IBMX mimics low 5HT concentrations (about 10(-7) M) by stimulating the L cilia to beat without affecting the beat frequency of the LF cirri. A combination of 10(-7) M 5HT and 0.5 mM IBMX in ASW mimics high (greater than 10(-6) M) 5HT concentrations by arresting the LF cirri and increasing the beat frequency of the L cilia. Under these conditions, the threshold of the LF cirri arrest response is again found to occur as the L cilia attain a beat frequency of 12-14 Hz. These results suggest that the mechanisms of LF cirri arrest and L cilia activation are mediated by 5HT-induced changes in intracellular cyclic AMP levels.
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PMID:The antagonistic effects of 5-hydroxytryptamine and methylxanthine on the gill cilia of Mytilus edulis. 241 3


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