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Biomedical subjects

M Léon

Publications and source records attributed to M Léon.

12 recordsLinked to original sources

Addition of enoximone to adrenergic agents in the management of severe heart failure.

OBJECTIVE: To assess the hemodynamic effects of the addition of small bolus doses of the phosphodiesterase inhibitor enoximone to adrenergic therapy in patients with severe heart failure. DESIGN: Open label, prospective study. SETTING: Multidisciplinary department of intensive care in a university academic hospital. PATIENTS: Twelve surgical patients after cardiac surgery and ten medical patients with ischemic or dilated cardiomyopathy who had signs of altered tissue perfusion associated with a low cardiac index (less than 2.25 L/min/m2), despite adrenergic therapy. INTERVENTIONS: Small iv bolus doses of 0.25 mg/kg of enoximone. MEASUREMENTS AND MAIN RESULTS: This treatment resulted in significant increases in cardiac index and left ventricular stroke work index without significant changes in heart rate or mean arterial pressure. Furthermore, the effects of half this dose (i.e., 0.125 mg/kg), studied in 11 patients, demonstrated a significant drug-induced increase in mean (+/- SD) cardiac index (from 1.58 +/- 0.29 to 1.84 +/- 0.27 L/min/m2, p less than .01) without change in mean arterial pressure (from 74.5 +/- 12.1 to 76.5 +/- 12.6 mm Hg, nonsignificant). CONCLUSIONS: Direct iv injections of enoximone can significantly increase the cardiac index in critically ill patients treated by adrenergic agents for severe heart failure. The administration of small doses of enoximone is effective and has minimal effect on arterial pressure.

Adult↗

Addition of phosphodiesterase inhibitors to adrenergic agents in acutely ill patients.

The addition of enoximone, a phosphodiesterase inhibitor, to adrenergic agents has been found useful in increasing cardiac output in severe heart failure. In one study of 13 patients in cardiogenic shock already receiving adrenergic support, enoximone was administered as a bolus of 0.5 mg/kg over 20 minutes. Pulmonary artery occlusion pressure decreased significantly from 21.7 +/- 5.8 mm Hg to 19.8 +/- 6.0 mm Hg (P less than 0.01) and cardiac index increased markedly. A second study investigated the effects of the addition of small boluses of enoximone to adrenergic agents in low flow states associated with heart failure (n = 8) or postoperative states after cardiac surgery (n = 10). Each of the 18 patients was treated with dobutamine; 12 patients were also treated with dopamine and 4 with noradrenaline. Enoximone was administered as small but increasing intravenous boluses. No significant change in mean arterial pressure was observed, but on 0.5 mg/kg of enoximone pulmonary artery occlusion pressure decreased significantly from 24.6 +/- 8.7 mm Hg to 19.4 +/- 9.9 mm Hg (heart failure) and from 18.2 +/- 3.3 mm Hg to 15.3 +/- 3.8 mm Hg (cardiac surgery) after the initial dose of 0.125 mg/kg. Cardiac index increased markedly after enoximone, 0.25 mg/kg. These changes were significant after the initial dose of 0.125 mg/kg. Thus, the addition of even small doses of enoximone to adrenergic agents can markedly increase cardiac index without significant effect on arterial pressure in medical or surgical cardiac patients.

Adult↗

The role of enoximone in the treatment of cardiogenic shock.

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.

Cardiac Output, Low↗

Antithrombin III synthesis in rat liver parenchymal cells.

We have previously demonstrated by immunoperoxydase the presence of immunoreactive antithrombin III (AT III) in rat hepatocytes. We now present direct evidence that rat hepatocytes in culture synthesize AT III like immunoreactive material : 35S-methionine was added to the culture medium and incubated with hepatocytes. After incubation, AT III was immunologically characterized in the medium. We found significant amounts of 35S-AT III among the radioactive proteins synthesized and secreted by the cells.

Animals↗

[Demonstration of a double subcellular localization of cerebral fucosyltransferase].

We have shown that the fucosyltransferase activity was located in two subcellular fractions: the microsomes and the synaptosomes. The localization of enzyme activity was identical in the young and in the adult rat brain. The values of some parameters of the microsomal enzyme (Km, optimum temperature, optimum pH) in the young and in the adult rat brain shown that the enzyme affinity for its substrate is in relation with the brain maturation.

Aging↗

Postnatal developmental changes in fucosyltransferase activity in rat brain.

GDP-fucose:asialofetuin fucosyltransferase activity was studied during the postnatal development of rat brain. The enzymatic activity was very low during the first days of life and reached a maximum level around 21 days. This increase in enzymatic activity was characterized by two periods of rapid change. A rapid increase occurred between 3 and 7 days after birth, followed by a slow increase from 7 to 17 days, then a new rapid change from 17 to 21 days. Stimulation of the enzymatic activity by Triton X-100 increased with age. The development profiles of GDP-fucose pyrophosphatase and fucosidase did not change during this period.

Age Factors↗

Recognition of tRNA Trp by initiation factors from Escherichia coli.

Binding of acetyl or formyltryptophanyl-tRNA Trp from Escherichia coli or beef liver to E. coli ribosomes is strongly stimulated by E. coli initiation factors and requires GTP. The N-acylated tryptophan is puromycin reactive. Polypeptide chain initiation with acetyltryptophan dependent on poly(U,G) has been demonstrated and is highly dependent on added initiation factors. tRNA Trp appears, therefore, to share some structural features with tRNAfMet of significance to the process of polypeptide chain initiation.

Escherichia coli↗