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A Descorps-Declère

Publications and source records attributed to A Descorps-Declère.

6 recordsLinked to original sources

Mechanical and electrophysiological effects of thiopental on rat cardiac left ventricular papillary muscle.

Thiopental induces a negative inotropic effect on mammalian heart muscle, where it decreases Ca2+ current and Ca2+ release from the sarcoplasmic reticulum and reduces K+ currents. We analysed the effects of thiopental on the mechanical and electrical activities of rat myocardium, which differ markedly from those of other mammals. The effects of thiopental on mechanical parameters and on the transmembrane resting (RP) and action (AP) potentials of rat left ventricular papillary muscle were investigated. These effects were also studied in the presence of atenolol, a beta-blocking agent, and 4-aminopyridine (4-AP), a blocker of the transient outward K+ current. Thiopental (3.8 x 10(-6), 3.8 x 10(-5) and 1.1 x 10(-4) M) induced a dose-dependent positive inotropic effect. This positive inotropic effect persisted in the presence of atenolol (1 x 10(-6) M) but did not develop in the presence of 1 mM 4-AP; 4-AP had a positive inotropic effect but not in the presence of thiopental. Moreover, thiopental (3.8 x 10(-5) M) lengthened the plateau and the slow repolarizing phase of the AP, while 1 mM 4-AP only prolonged the plateau duration. In rat myocardium, the positive inotropic effect of thiopental in part mimics that of 4-AP, and in part may be explained by the lengthening of the slow repolarizing phase of the AP.

Action Potentials↗

Effects of halothane on the membrane potential in skeletal muscle of the frog.

Halothane has many effects on the resting membrane potential (V(m)) of excitable cells and exerts numerous effects on skeletal muscle one of which is the enhancement of Ca(2+) release by the sarcoplasmic reticulum (SR) resulting in a sustained contracture. The aim of this study was to analyse the effects of clinical doses of halothane on V(m), recorded using intracellular microelectrodes on cleaned and non stimulated sartorius muscle which was freshly isolated from the leg of the frog Rana esculenta. We assessed the mechanism of effects of superfused halothane on V(m) by the administration of selective antagonists of membrane bound Na(+), K(+) and Cl(-) channels and by inhibition of SR Ca(2+) release. Halothane (3%) induced an early and transient depolarization (4.5 mV within 7 min) and a delayed and sustained hyperpolarization (about 11 mV within 15 min) of V(m). The halothane-induced transient depolarization was sensitive to ryanodine (10 microM) and to 4-acetamido-4'-isothiocyanatostilbene 2,2' disulphonic acid (SITS, 1 mM). The hyperpolarization of V(m) induced by halothane (0.1 - 3%) was dose-dependent and reversible. It was insensitive to SITS (1 mM), tetrodotoxin (0.6 microM), and tetraethylammonium (10 mM) but was blocked and/or prevented by ryanodine (10 microM), charybdotoxin (CTX, 1 microM), and glibenclamide (10 nM). Our observations revealed that the effects of halothane on V(m) may be related to the increase in intracellular Ca(2+) concentration produced by the ryanodine-sensitive Ca(2+) release from the SR induced by the anaesthetic. The depolarization may be attributed to the activation of Ca(2+)-dependent Cl(-) (blocked by SITS) channels and the hyperpolarization to the activation of large conductance Ca(2+)-dependent K(+) channels, blocked by CTX, and to the opening of ATP-sensitive K(+) channels, inhibited by glibenclamide.

Anesthetics, Inhalation↗

Assessment of gastric mucosal perfusion during simulated hypovolemia in healthy volunteers.

We described here an original device for laser Doppler (LD) flowmetry measurements of gastric mucosal perfusion, which was used here in healthy volunteers. A modified nasogastric tube containing the LD probe was inserted. Aspiration via a catheter, fixed in parallel to the probe, held the probe against the gastric wall. This new device was used to assess gastric mucosal perfusion in seven volunteers during simulated hypovolemia induced by lower body negative pressure (LBNP) application. The LBNP consisted of three successive levels of depression (-10, -20, and -30 mm Hg). Although mean arterial pressure remained unchanged during negative pressure application, there was a significant decrease in cardiac output (transthoracic electrical impedance) at each stage of LBNP. In contrast, gastric mucosal perfusion decreased significantly only at higher level of sympathetic stimulation corresponding to unloading of both cardiopulmonary and arterial baroreflexes (-30 mm Hg). It may be hypothetized that local vascular mechanisms exist to maintain gastric mucosal perfusion during moderate sympathetic stimulation induced by selective unloading of cardiopulmonary receptors. In the healthy volunteers studied, we found that LD flowmetry is a valuable tool to evaluate gastric mucosal perfusion when the probe is maintained in a constant position by the technique described here.

Adult↗

Role of systemic inflammatory response syndrome and infection in the occurrence of early multiple organ dysfunction syndrome following severe trauma.

OBJECTIVE: To evaluate the role of infection and systemic inflammatory response syndrome (SIRS) on the occurrence of early posttraumatic MODS. DESIGN: Retrospective study. SETTING: University Teaching Hospital ICU. PATIENTS: 163 consecutive patients hospitalized for more than 48 hours following severe trauma. MEASUREMENTS AND MAIN RESULTS: The patients were classified into two groups in respect to the existence of MODS at day 2. There was 27 patients in the MODS group and 136 patients in the no MODS group. The two groups were similar with respect to age, sex ratio and Simplified Acute Physiology Score. The MODS group had a higher mortality (52 versus 7%), Injury Severity Score (45 +/- 14 versus 31 +/- 13), hypovolemic shock rate (74 versus 30%), massive volume replacement rate (59 versus 6%) and SIRS rate (81 versus 54%) than the no MODS group (P < 0.05). The rate of infection was similarly low in the MODS and no MODS group (4 versus 6% respectively). CONCLUSION: Early MODS is often associated with hypotension and massive volume administration but very rarely with infection, despite the high rate of SIRS.

Adult↗

A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer.

A significant increase in the dose intensity of chemotherapy with fluoropyrimidines and platinum complexes has resulted from selective circadian timing and/or circadian modulation of the infusion rate. The relevance of such chronopharmacologic strategy for improving the outcome of metastatic colorectal cancer was evaluated in an extended Phase II clinical trial involving 93 patients. Of these, 49% previously had received chemotherapy and/or radiation therapy. The drugs 5-fluorouracil (5-FU, 700 mg/m2/d) and folinic acid (FA, 300 mg/m2/d) combined with oxaliplatin (l-OHP, a nonnephrotoxic platinum complex, 25 mg/m2/d) were infused continuously for 5 days every 3 weeks. In a pilot randomized study, the infusion of all three drugs at a constant rate resulted in World Health Organization (WHO) Grade 3 or 4 toxicity in all four patients compared with no such toxicity in four patients if the infusion rate was modulated according to circadian rhythms. In this Phase II trial, drug delivery was modulated sinusoidally over the 24-hour day with peak flow rates at 4 AM for 5-FU and FA and at 4 PM for l-OHP, using an ambulatory programmable-in-time pump. All patients and 784 of 839 courses (93%) were evaluable for toxicity. Dose-limiting toxicities (WHO Grade 2 to 4) included diarrhea (19% of courses) and vomiting (35% of courses). In addition, WHO Grade 2 to 4 hematologic or mucosal toxicity, respectively, occurred in 2.5% and 7% of courses. Two toxic deaths were encountered. Peripheral sensory neuropathy led to discontinuation of l-OHP in 14 patients after 7 to 12 courses; it completely disappeared within 3 months. Fifty-four of the 93 patients had an objective response (58%; 95% confidence limits, 48% to 68%), irrespective of previous treatment or prior documented progression while receiving standard chemotherapy with 5-FU and FA or continuous 5-FU. Complete responses (CR) were seen in 6 patients (4 of which were proved histologically) and, after surgery, in 12 additional patients (overall CR rate, 18 of 93 [19%]; 95% confidence limits, 11% to 27%). Median progression-free survival (PFS) and overall survival were, respectively, 10 and 15 months, irrespective of prior therapy. Both PFS and survival were significantly longer in patients with a good performance status (PS, 0 or 1, by WHO criteria; respectively, 12 and 21 months) than in patients with poor PS (respectively, 8 and 10 months; P less than 0.01, by log-rank test). This chronopharmacologic protocol may have circumvented, to some extent, both the natural and acquired resistance of colorectal cancer to chemotherapy.

Adult↗