Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atrial natriuretic peptide lowers arterial pressure and increases hematocrit through reduction in plasma volume caused by a transcapillary shift of plasma fluid and protein toward the interstitium. Cyclic GMP, the second messenger of atrial natriuretic peptide is catabolized by cGMP-phosphodiesterase; therefore we examined the consequences of inhibition of the phosphodiesterase on these responses using the specific cGMP inhibitor M&B 22.948. In anesthetized, bilaterally nephrectomized rats, a 45-min infusion of atrial natriuretic peptide (1 microgram/kg/min) reduced arterial pressure by 7.6 +/- 1.5% and increased hematocrit by 9 +/- 0.6% (both p < 0.01), leading to a calculated decrease in plasma volume of 14.4 +/- 0.9%. Infusion of M&B 22.948 (0.68 mg/kg/min) did not affect hematocrit and lowered arterial pressure by 8.1 +/- 0.5% (p < 0.01), an effect similar to that observed following administration of sodium nitroprusside (10 micrograms/kg/min). Simultaneous infusion of atrial natriuretic peptide and M&B 22.948 had additive arterial pressure lowering effects (-15.9 +/- 1.1%; p < 0.01 vs atrial natriuretic peptide or M&B 22.948 alone), while the increase in hematocrit of 9.4 +/- 0.7% was identical to that seen with atrial natriuretic peptide alone. Thus, M&B 22.948 amplified atrial natriuretic peptide effects on arterial pressure, but not on vascular permeability. These findings indicate differential regulation of atrial natriuretic peptide effects by inhibition of the cGMP-phosphodiesterase.
Arch Mal Coeur Vaiss 1992 Aug
PMID:[Modulating effects of atrial natriuretic peptide on vascular permeability and blood pressure by inhibition of cyclic phosphodiesterase GMP in the rat]. 133 59

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.
Arch Mal Coeur Vaiss 1991 Nov
PMID:[Hemodynamic effects of milrinone in the treatment of cardiac insufficiency after heart surgery with extracorporeal circulation]. 176 24

Ten patients with cardiogenic shock after acute myocardial infarction were referred to the University Hospital Henri Mondor as candidates for cardiac transplantation. The period before transplantation was bridged by maximal pharmacological support including sympathomimetic and phosphodiesterase inhibitor inotropic agents and, in non-responders, by mechanical ventricular assist devices (1 case) or artificial hearts (2 cases). The 7 patients who improved with optimal pharmacological support alone had a good initial course. However, only two of these patients were finally transplanted, three died suddenly either in the intensive care unit or after withdrawal of intravenous drugs and hospital discharge. One patient remained well and after coronary bypass surgery, enjoys good quality life. One patient was found secondarily to be a poor candidate for transplantation and died shortly after. The outcome of 2 of the 3 patients who did not respond to pharmacological treatment and who required mechanical support was spectacularly good and enabled successful cardiac transplantation. Our experience underlines the numerous difficulties of different natures of cardiac transplantation in this indication, the value and risks of the new inotropic agents, and the real but limited role of heroic procedures such as the artificial heart.
Arch Mal Coeur Vaiss 1991 Jun
PMID:[Heart transplantation in acute myocardial infarction]. 183 53

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)
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Medical strategy in patients awaiting emergency heart transplantation]. 214 25

Enoximone, a phosphodiesterase inhibitor, is a positive inotropic agent with direct vasodilator properties. Its acute effects after I.V. administration and the possibility of oral relay were studied in 14 patients (13 men and 1 woman), 40 to 78 years of age (mean 61 years) with Stage IV cardiac failure (NYHA Classification). Eleven patients had dilated cardiomyopathy, 2 had ischemic heart disease and 1 a dilated hypertrophic cardiomyopathy. The haemodynamic inclusion criteria were: cardiac index less than or equal to 2.2 l/mn/m2 and pulmonary capillary pressure greater than or equal to 18 mmHg. Patients with cardiogenic shock and severe renal or hepatic failure were excluded. The drug was administered as a bolus of 1 mg/kg followed by a continuous infusion of 5 to 15 g/kg/mn (average 8.9 +/- 2.6 for 7 to 72 hours; average 27 +/- 16 hours). Haemodynamic effects of I.V. administration: no change in heart rate, slight lowering of blood pressure, very significant reduction in right atrial and pulmonary capillary pressures, of pulmonary artery pressures, of arteriolo-capillary and systemic resistances and marked increase in cardiac output. General tolerance was excellent with no clinical secondary effects and no signs of hepatic, renal or haematological (platelets) toxicity. Cardiac tolerance was also excellent, no aggravation of preexisting arrhythmias. There was no immediate mortality. Oral relay was undertaken in 14 patients with a daily dose of 300 mg in 12 cases, 400 mg in 1 case and 500 mg in 1 case. Six patients underwent control haemodynamic evaluation on the 8th day: there were no signs of the haemodynamic improvement obtained by I.V. administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Enoximone: hemodynamic effect in patients with cardiac insufficiency]. 214 30

In severe chronic congestive cardiac failure the physician has the choice of two families of positive inotropic agents, the direct sympathomimetics and the phosphodiesterase inhibitors. The aim of the study was to compare the efficacy and tolerance of enoximone and dobutamine in this indication. Twenty patients with severe chronic cardiac failure with a cardiac index of less than 2.2 l/min/m2 and pulmonary capillary pressure of over 20 mmHg were randomised into two groups in an open trial. One group received enoximone 50 micrograms/kg/min for 30 minutes then 10 micrograms/kg/min and the other received dobutamine 10 micrograms/kg/min. The two groups were comparable. Results were analysed 12 hours after starting therapy, well after the loading dose of enoximone and before the appearance of tolerance to dobutamine. Neither drug caused a significant change in heart rate or mean blood pressure. The pressure-rate product did not increase significantly with enoximone (+9.2% NS) in contrast with the dobutamine group in which a significant elevation was observed (+23.5%, p less than 0.05). The cardiac index increased with enoximone (+61.0%, p less than 0.01) and with dobutamine (+32.1%, p less than 0.02). This resulted mainly from an increase in the systolic index (+45.5%, p less than 0.05 with enoximone and +30.1%, p less than 0.05 with dobutamine). Pulmonary capillary pressure and total systemic resistance decreased with enoximone (-29.1%, p less than 0.001 and -36.7%, p less than 0.05 respectively) and with dobutamine (-23.4%, p less than 0.001 and -20.7%, p less than 0.05 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Enoximone/dobutamine comparison in chronic congestive cardiac insufficiency with low cardiac output]. 214 31

Theoretically, there are two reasons for using the association of dobutamine and enoximone in patients with acute cardiac failure; the powerful vasodilator effect of enoximone and the different biochemical actions of the two drugs on the myocardial fibre affecting the production (dobutamine) or the degradation (enoximone) of cyclic AMP. The combined effects of beta adrenergic agonists and phosphodiesterase III inhibitors in vitro and in vivo have been previously reported. An increased contractile response to dobutamine has been demonstrated with enoximone on isolated human ventricle obtained during cardiac transplantation. We confirmed the additive effect of dobutamine (5 to 10 micrograms/kg/min) and enoximone (1 mg/kg/bolus IV) in 8 patients with acute cardiac failure with each molecule used alone. Mild changes in heart rate (+19 bpm) and in systolic blood pressure (-3 mmHg) were observed simultaneously. The absence of an increase in SvO2 compared to the use of each molecule in monotherapy is probably related to a tendency to increase myocardial oxygen consumption which may be potentially deleterious in terms of gas exchange. Having demonstrated the additive effects of the association of dobutamine and enoximone, there is probably a place for this therapeutic association in the management of acute cardiac failure. However, the potential risk of inducing an atrial and/or ventricular tachyarrhythmia and the consequences of lowering ventricular filling pressures and systemic vascular resistances should be born in mind; when using this therapeutic association, the authors suggest starting treatment with low doses of dobutamine (5/kg/min) and enoximone (0.5 - 1 mg/kg) with haemodynamic control and steadily increasing the doses, depending on the results obtained.
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Role of the enoximone-dobutamine combination in the treatment of congestive cardiac insufficiency]. 214 32

Forty patients developed low cardiac output states after surgery for mitral valve disease or with associated cardiac disease and were randomly allocated to two treatment groups, one group to receive Dobutamine (D) and the other Enoximone (E), a phosphodiesterase inhibitor. Haemodynamic assessment covered a 24 hour period but treatment was continued for as long as was necessary. An improvement was observed from the 15th minute of treatment. At the second hour, the cardiac index had increased by 55% in Group E and by 59% in Group D whilst the heart rate increased by only 12% in Group E compared to 30% in Group D. The right and left heart filling pressures decreased by 25 to 27% in the 2 groups. The systemic arterial resistances fell by 36 to 37% without any significant changes in systemic or pulmonary arterial pressures. No significant difference was demonstrated in the haemodynamic responses to Dobutamine and Enoximone in this study. The duration of treatment was significantly shorter in Group E than in Group D (59 +/- 22 hrs vs 86 +/- 49 hrs) as was the patient's stay in the intensive care unit (92 +/- 37 hrs vs 155 +/- 129 hrs). The duration of assisted ventilation was the same in the two groups. These results suggest that Enoximone is as effective as Dobutamine in the treatment of low cardiac output after mitral valve surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Comparison of the hemodynamic effects of dobutamine and enoximone in the treatment of low cardiac output after valvular surgery]. 214 36

Mechanical ventilation is a valuable therapeutic option in left ventricular failure because of its effect on ventricular load. However, weaning cardiac patients form mechanical ventilation may result in severe pulmonary oedema, especially if it is not properly prepared. Some of the factors which contribute to pulmonary oedema are: 1) increased venous return due to the inversion ot the regime of inthrathoracic pressures and the release of catecholamines commonly observed during weaning, 2) reduction of left ventricular compliance due to myocardial ischemia, compression of the cardiac chambers by the lungs, ventricular interdependence in some cases and left ventricular dilatation in others, 3) increased left ventricular afterload due to negative intrathoracic pressures and increased systolic blood pressure. Of all the causes of unsuccessful weaning, left ventricular dysfunction should be carefully considered because its treatment alone may enable the patients to be taken off the ventilator. The authors report six cases of pulmonary oedema in coronary patients after discontinuing mechanical ventilation. The administration I.V. enoximone, a phosphodiesterase inhibitor, prevented acute left ventricular dysfunction in 5 of the 6 cases and enabled successful and definitive weaning from mechanical ventilation.
Arch Mal Coeur Vaiss 1990 Sep
PMID:[Left ventricular dysfunction while weaning from mechanical ventilation. Contribution of enoximone]. 214 40

Enoximone is a positive inotropic agent belonging to the group of phosphodiesterase F-III inhibitors. The drug was tested in 34 patients uncontrolled by sympathomimetic drugs and referred to our department for urgent heart transplantation or circulatory assistance. After insertion of a Swan-Ganzgatheter and a radial artery catheter for haemodynamic monitoring, enoximone was administered as a 15-minute intravenous bolus injection of 1 to 2.5 mg/kf every 8 hours, in addition to sympathomimetic agents. Clinical and haemodynamic improvement was observed after thirty minutes in 30 patients. The cardiac index rose from 1.82 to 2.67 l/min/m2 and the pulmonary wedge pressure fell from 30.8 to 18.9 mmHg. Systemic arterial resistance decreased from 2170 to 1520 dyn. s. cm-5, and pulmonary resistance from 5.5 to 4.6 Wood units (p less than 0.01 for all values). Four patients had no haemodynamic improvement and were put on circulatory assistance, using a Jarvik 7 total artificial heart in 3 of them and heterotopic circulatory assistance in one. After clinical investigation for contra-indication to heart transplantation, and as their improved haemodynamic status permitted, 12 of the 30 patients were considered suitable (group B) for heart transplantation. Transplantation was performed within a week of admission in 11 patients without any need for mechanical assistance. One of the group B patients who required implantation of a Jarvik 7 artificial heart died after 12 hours of assistance. Eighteen patients were considered unsuitable for transplantation (group A) and treated medically.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss
PMID:[Enoximone and the therapeutic strategy in patients awaiting emergency cardiac graft]. 252 34


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