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Biomedical subjects

O Langeron

Publications and source records attributed to O Langeron.

At least 37 records · Page 2Linked to original sources

The effects of dantrolene on the contraction, relaxation, and energetics of the diaphragm muscle.

UNLABELLED: Dantrolene is used in patients with muscle spasticity and is the only known effective treatment for malignant hyperthermia. However, its effects on muscle relaxation and energetics are unknown and may have important consequences in diaphragmatic function. We studied the effects of dantrolene (10(-8) to 10(-4) M) on diaphragm muscle strips (n = 12) in the hamster in vitro (Krebs-Henseleit solution, 29 degrees C, 95% oxygen/5% carbon dioxide) in response to tetanic stimulation (50 Hz). We studied contraction and relaxation under isotonic and isometric conditions, as well as energetics. Data are mean +/- SD. Dantrolene induced a negative inotropic effect in the hamster diaphragm (active force at 10(-4) M: 34% +/- 7% of baseline; P < 0.05) but did not significantly modify the curvature of the force-velocity relationship. Dantrolene did not significantly modify isotonic relaxation. Dantrolene, up to 10(-5) M, did not significantly impair isometric relaxation. In conclusion, dantrolene induced a marked negative inotropic effect on diaphragm muscle without affecting myothermal efficiency and relaxation. IMPLICATIONS: Dantrolene induced a significant and concentration-dependent negative inotropic effect on diaphragm muscle but did not modify isotonic relaxation, which suggests no alteration of the calcium reuptake by the sarcoplasmic reticulum; up to 10(-5) M dantrolene did not alter isometric relaxation, i.e., myofilament calcium sensitivity. Dantrolene did not modify the energetics of diaphragm muscle.

Animals↗

Impaired load dependence of diaphragm relaxation during congestive heart failure in the rabbit.

The load dependence (LD) of relaxation was studied in the diaphragm of rabbits with congestive heart failure (CHF). CHF (n = 15) was induced by combined chronic volume and pressure overload. Aortic insufficiency was induced by forcing a catheter through the aortic sigmoid valves, followed 3 wk later by abdominal aortic stenosis. Six weeks after the first intervention, animals developed CHF. Sham-operated animals served as controls (C; n = 12). Diaphragm mechanics were studied in vitro on isolated strips, at 22 degrees C, in isotonic and isometric loading conditions. Contractility was lower in the CHF group, as reflected by lower total tension: 1.11 +/- 0.10 in CHF vs. 2.38 +/- 0.15 N/cm(2) in C in twitch (P < 0.001) and 2.46 +/- 0.22 in CHF vs. 4.90 +/- 0.25 N. cm(-2) in C in tetanus (P < 0.001). The index LD was used to quantify the load dependence of relaxation: LD is <1 in load-dependent muscles and tends toward 1 in load-independent muscles. LD was significantly higher in CHF than in C rabbits, in both twitch (0.99 +/- 0.01 vs. 0.75 +/- 0.03; P < 0. 001) and tetanus (0.95 +/- 0.02 vs. 0.84 +/- 0.02; P < 0.001). In the CHF rabbits' diaphragm, the fall in total tension was linearly related to the fall in load dependence of relaxation. The decrease in load dependence of relaxation in CHF animals suggests sarcoplasmic reticulum abnormalities. Impairment of the sarcoplasmic reticulum may also partly account for the decrease in contractile performance of diaphragm in CHF animals.

Animals↗

Impaired skeletal muscle performance in the early stage of cardiac pressure overload in rabbits: beneficial effects of angiotensin-converting enzyme inhibition.

Abnormalities of skeletal muscles are frequently observed in patients with congestive heart failure. In these patients, angiotensin-converting enzyme (ACE) inhibitors improve exercise performance. The present study was designed to assess whether skeletal muscle dysfunction develops in the early stage of cardiac overload and if so, whether such functional alterations can be prevented by ACE inhibition. Mechanical performance, cross-bridge (CB) properties, and myosin heavy chain composition were investigated in respiratory and limb skeletal muscles of rabbits with moderate cardiac hypertrophy, and after single therapy with the ACE inhibitor perindopril (PE). After constriction of the aorta, the rabbits were treated during a 10-week period with either PE (1 mg/kg/day; n = 9) or a placebo (PL; n = 15). A third group of sham-operated animals received PL (n = 10). Analyses were performed on isolated diaphragm and soleus strips. Compared with sham-operated animals (shams), peak tetanic tension in PL fell by 40% in diaphragm and 34% in soleus. There were no significant differences in peak tetanic tension and the maximum shortening velocity between PE and shams. In both muscles, the total number of CBs was significantly lower in PL than in shams, but did not differ between shams and PE. The elementary force per CB did not differ between groups. In both muscles, the myosin heavy chain composition did not differ between groups. The study demonstrated that intrinsic performance of diaphragm and soleus muscles was affected early in the development of chronic pressure overload. Single therapy with PE tended to preserve muscle strength, essentially by limiting the loss of CBs.

Angiotensin-Converting Enzyme Inhibitors↗

Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction.

BACKGROUND: Long-term postoperative cognitive dysfunction may occur in the elderly. Age may be a risk factor and hypoxaemia and arterial hypotension causative factors. We investigated these hypotheses in an international multicentre study. METHODS: 1218 patients aged at least 60 years completed neuropsychological tests before and 1 week and 3 months after major non-cardiac surgery. We measured oxygen saturation by continuous pulse oximetry before surgery and throughout the day of and the first 3 nights after surgery. We recorded blood pressure every 3 min by oscillometry during the operation and every 15-30 min for the rest of that day and night. We identified postoperative cognitive dysfunction with neuropsychological tests compared with controls recruited from the UK (n=176) and the same countries as study centres (n=145). FINDINGS: Postoperative cognitive dysfunction was present in 266 (25.8% [95% CI 23.1-28.5]) of patients 1 week after surgery and in 94 (9.9% [8.1-12.0]) 3 months after surgery, compared with 3.4% and 2.8%, respectively, of UK controls (p<0.0001 and p=0.0037, respectively). Increasing age and duration of anaesthesia, little education, a second operation, postoperative infections, and respiratory complications were risk factors for early postoperative cognitive dysfunction, but only age was a risk factor for late postoperative cognitive dysfunction. Hypoxaemia and hypotension were not significant risk factors at any time. INTERPRETATION: Our findings have implications for studies of the causes of cognitive decline and, in clinical practice, for the information given to patients before surgery.

Abdomen↗

Effects of dantrolene on the diaphragm muscle of the normal and myopathic hamster.

Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on the myopathic diaphragm remain unknown. The effects of dantrolene 10(-8) to 10(-4) mol litre-1 on diaphragm muscle strips in normal (n = 12) and myopathic hamsters (n = 13) were investigated in vitro in response to tetanic stimulation. We studied contraction under isotonic and isometric conditions. Data are presented as mean (SD) percent of baseline. Dantrolene induced a negative inotropic effect in normal and myopathic hamsters but no significant difference was observed between groups (active force at 10(-4) mol litre-1; 34 (7) vs 32 (11)%; ns). We conclude that dantrolene induced a comparable negative inotropic effect on diaphragm muscle in normal and myopathic hamsters.

Animals↗

[Assessment of a new light guide (Trachlight) for tracheal intubation].

OBJECTIVE: To assess the learning curve of a new lighwand device, Trachlight (Laerdal), for blind orotracheal intubation in patients without foreseen difficulty in airway management. STUDY DESIGN: Open, prospective, clinical study. USERS: Twelve persons practicing anaesthesia (specialists, trainees, nurses) underwent videotape learning and manikin training with ten successful intubation manoeuvres required with the device. METHODS: Each person had to carry out a tracheal intubation in ten consecutive patients undergoing scheduled surgery and without history or clinical sign of difficults airway management. RESULTS: One hundred and twenty patients were included. The overall success rate with the Trachlight was 87%. An easy learning curve was obtained as demonstrated by the low failure rate in the first three patients, and by the success rate on the first or second attempt in the last four patients. There was no significant difference in failure rate with or without muscle relaxation (10 vs 20%, NS). Finally, all failures with the Trachlight were followed by successful intubation using direct laryngoscopy, and no traumatic complications were recorded with the device. CONCLUSION: Trachlight is a new lightwand device enabling blind tracheal intubation with a easy learning curve in patients without difficulty in airway management, even for non-selected operators.

Adult↗

Infection risk and cost-effectiveness of commercial bags or glass bottles for total parenteral nutrition.

OBJECTIVE: To determine whether the greater daily expense of administering total parenteral nutrition (TPN) via plastic bags changed once daily, compared to glass bottles changed thrice daily, could be offset by savings from a reduction in nosocomial infections. DESIGN: The costs and potential benefits of commercially available TPN bags and TPN in glass containers were compared. Costs were computed from the viewpoint of the hospital, first in a general model and then for two specific examples, Crohn's disease and intensive-care unit (ICU) patients. The extra cost of using bags was $20 per day. The total cost of nosocomial bacteremia was estimated at $6,000. The monetary benefits of using TPN bags were $6,000XT, where XT was the percentage of nosocomial infections averted. We also considered that reduction in intravenous (IV)-line manipulation could reduce bacteremia-related mortality and computed a cost-per-life-saved ratio. RESULTS: Modeling showed that TPN in bags could yield a net benefit when the absolute reduction in the daily risk of nosocomial bacteremia reached the threshold value of 0.3%. Such a reduction could not be attained in patients with Crohn's disease, and corresponded to a 50% to 60% reduction of infection rates in ICU patients. Varying the risk of mortality attributable to IV-line-related infection from 1% to 13% resulted in a cost effectiveness of using TPN bags ranging from $90,000 to $7,000 per life saved in ICU, assuming a two-thirds reduction in IV-line infections, and from $180,000 to $14,000 if the infection rate was reduced by one third. CONCLUSION: The baseline cost-minimization analysis concluded that the extra cost of TPN bags was not justified by the extra savings. The cost-effectiveness analysis, however, found that the cost per life saved fell within the accepted range of public health interventions, provided a large fraction of infections are averted using TPN bags.

Cost-Benefit Analysis↗

Comparison of the effects of ketamine-midazolam with those of fentanyl-midazolam on cortical somatosensory evoked potentials during major spine surgery.

Cortical somatosensory evoked potentials (CSEP) allow monitoring of spinal cord function during surgery. Ketamine has been shown to enhance CSEP amplitude, but there is no previous study comparing its effects with those of other anaesthetic regimens. Therefore, we have compared the effects of ketamine with those of fentanyl, both combined with midazolam, on CSEP monitoring during major spine surgery. Twenty patients with normal preoperative CSEP were allocated randomly to a ketamine or fentanyl group. Anaesthesia was induced with ketamine 3 mg kg-1 or fentanyl 6 micrograms kg-1 i.v., and midazolam 0.3 mg kg-1 i.v in both groups, and maintained with continuous i.v infusion of ketamine 2 mg kg-1 h-1 or fentanyl 3 micrograms kg-1 h-1, combined in both groups with midazolam 0.15 mg kg-1 h-1 and 60% nitrous oxide in oxygen. CSEP were elicited by tibial posterior nerve stimulation and measured P1 and N1 latencies, and P1-N1 amplitude, CSEP were recorded before and after induction, at 15 min, 1 and 2 h after induction, during skin closure and after removal of nitrous oxide. Both groups were comparable in characteristics, duration of surgery, mean arterial pressure and temperature. CSEP latencies were not significantly affected in either group. CSEP amplitude decreased significantly over time in the fentanyl group (from mean 2.02 (SEM 0.41) to 0.95 (0.17) microV, P < 0.05), but not in the ketamine group (from 1.33 (0.36) to 1.05 (0.31) microV, ns). Nevertheless, we did not observe any significant differences in amplitudes or latencies between the two groups. The delay in obtaining the first voluntary postoperative motor response was significantly greater in the ketamine group (170 (54) vs 55 (17) min, P < 0.01). Both ketamine and fentanyl allowed us to obtain reliable CSEP during major spine surgery, and there were no significant difference between these two anaesthetic regimens for CSEP monitoring, but a longer delay for voluntary postoperative motor assessment was observed in the ketamine group.

Adult↗

In vitro effects of dantrolene on rat myocardium.

BACKGROUND: Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on myocardial contraction and relaxation remain debatable. METHODS: The effects of dantrolene (10(-5)-10(-3) M) on the contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, 2.5 and 0.5 mM Ca2+, stimulation frequency 12 pulses/min). The authors studied contraction, relaxation, contraction-relaxation coupling under high and low load, energetics, and postrest potentiation. The effects of dantrolene after depletion of catecholamine stores with reserpine also were studied. RESULTS: Dantrolene induced a moderate concentration-dependent negative inotropic effect at a low calcium concentration (active force at 10(-4) M: 86 +/- 14% of control values, P < 0.05), but not at a high calcium concentration. Dantrolene did not significantly modify the curvature of the force-velocity relation, suggesting that it did not modify myocardial energetics. Dantrolene induced no significant lusitropic effect under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Dantrolene did not significantly modify postrest potentiation and postrest potentiation recovery, suggesting that it did not modify maximum capacity of calcium release by the sarcoplasmic reticulum nor its postrest resetting capacity. Reserpine did not modify the myocardial effects of dantrolene. CONCLUSIONS: In rat myocardium, dantrolene did not modify any of the sarcoplasmic reticulum functions tested (uptake, release, postrest recovery). Dantrolene induced a moderate negative inotropic effect, probably mediated by a decrease in transarcolemmal calcium entry, and this negative inotropic effect was blunted by an increase in calcium concentration.

Animals↗

Oxygen consumption and delivery relationship in brain-dead organ donors.

The oxygen delivery (DO2) and consumption (VO2) relationship in brain-dead organ donors is unknown. Therefore, in a prospective study, we determined the DO2/VO2 relationship in 21 consecutive brain-dead patients. Patients were allocated to one of two groups, according to plasma lactate concentration: normal (group NL, n = 11) or high (> 2.5 mmol litre-1) (group HL, n = 10). VO2 was measured independently, using indirect calorimetry, under control conditions, during low DO2 challenge with PEEP administration, and high DO2 challenge with inflation of medical antishock trousers and volume expansion or blood transfusion, as required. Under control conditions, there were no significant differences between groups NL and HL in haemodynamic or oxygenation variables, both groups having a low VO2 (mean 114 (SD 21) ml min-1 m-2). In group HL there was a different DO2/VO2 relationship pattern, with a dependent VO2 only. The mean slope of the DO2/VO2 relationship was significantly higher in group HL than in group NL (0.12 (0.09) vs 0.04 (0.07), P < 0.05). We conclude that brain death was associated with a low VO2, and patients in group HL exhibited DO2/VO2 dependency which was not observed in patients in group NL.

Adolescent↗

[Combination of propofol-sufentanil on somatosensory evoked potentials in surgery of the spine].

OBJECTIVES: Most anaesthetics depress cortical somatosensory evoked potentials (CSEPs). However, the modification of CSEPs during total intravenous anaesthesia using propofol remaining still unknown, justified this trial. TYPE OF STUDY: Open, prospective, clinical study. METHODS: Nine consecutive patients requiring CSEPs monitoring for spine surgery, were studied. Anaesthesia was induced with propofol (2.5 mg.kg-1 then 10 mg.kg-1.h-1) and sufentanil (0.50 micrograms.kg-1 then 0.25 micrograms.kg-1.h-1). Maximum positive (P40) and negative (N50) waweform latencies, and the peak to peak amplitude of CSEPs (posterior tibial nerve stimulation, cortical recording), were recorded before induction, 30 min, 1 and 2 h after induction, and at the end of surgery. Data are means +/- SD. RESULTS: Duration of anaesthesia was 260 +/- 73 min. Propofol induced significant lengthening of CSEPS (P40: from 37 +/- 10 up to 41 +/- 11 ms; N50: from 45 +/- 11 up to 51 +/- 14 ms), and a significant decrease in amplitude (from 1.9 +/- 0.9 down to 0.8 +/- 0.4 microV), but these changes were stable from 30 min after the induction to the end of spine surgery. A motor response was obtained 29 +/- 14 min after the end of anaesthetic administration. CONCLUSIONS: Total intravenous anaesthesia with propofol and sufentanil induces a small but stable lengthening of CSEPs latency and a stable decrease of its amplitude, which enable an appropriate monitoring of CSEPs during spine surgery.

Adult↗

In vitro effects of eltanolone on rat myocardium.

BACKGROUND: Eltanolone is a new short-acting intravenous induction agent. However, its effects on intrinsic myocardial contractility remain unknown. METHODS: The effects of eltanolone and its solvent (soya bean emulsion) on the intrinsic contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca2+ 0.5 mM, stimulation frequency 12 pulses/min). We studied contraction; relaxation; contraction-relaxation coupling under high and low loads; and postrest potentiation. RESULTS: Eltanolone (0.1, 0.3, 1, 3, and 10 micrograms.ml-1) induced no significant inotropic effect, as shown by the lack of changes in maximum unloaded shortening velocity and active isometric force. Eltanolone did not significantly modify the contraction-relaxation coupling under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Eltanolone did not significantly modify the contraction-relaxation coupling under high load, suggesting that it did not modify calcium myofilament sensitivity. Eltanolone decreased the postrest potentiation in a concentration-dependent manner (from 150 +/- 14% to 118 +/- 9% at 10 micrograms.ml-1, P < 0.001), suggesting a decrease in the maximum capacity of calcium release by the sarcoplasmic reticulum, whereas its solvent did not. However, eltanolone did not slow postrest potentiation recovery, as shown by the absence of significant changes in the recovery slope, tau (4.5 +/- 1.4 vs. 3.8 +/- 1.0 beats; difference not statistically significant). CONCLUSIONS: Eltanolone induced no significant inotropic effect on rat myocardium. It induced a decrease in the calcium release function of the sarcoplasmic reticulum, but this effect was not sufficiently important to modify the inotropic properties.

Anesthetics, Intravenous↗

Additive effect on gas exchange of inhaled nitric oxide and intravenous almitrine bismesylate in the adult respiratory distress syndrome.

OBJECTIVE: To assess the additive effect of inhaled nitric oxide (NO) and intravenous almitrine bismesylate (ALM) on gas exchange. DESIGN: Prospective self-controlled study. SETTING: 3 medico-surgical intensive care units. PATIENTS: 17 patients with severe hypoxemia (PaO2/FIO2 ratio: 88 +/- 30 mmHg, venous admixture: 47 +/- 7%) and elevated mean pulmonary artery pressure (MPAP: 30 +/- 5 mmHg) due to adult respiratory distress syndrome (ARDS). INTERVENTIONS: 5 conditions were studied: 1) baseline, 2) 5 to 10 ppm of NO during 30 min, 3) discontinuation of NO during 30 min, 4) ALM infusion (0.5 mg/kg) during 30 min, 5) ALM infusion (0.5 mg/kg) during 30 min in combination with 5 to 10 ppm of NO. MEASUREMENT AND RESULTS: The PaO2/FIO2 ratio rose from 88 +/- 30 to 98 +/- 37 mmHg (NS) with NO alone, and from 92 +/- 25 to 130 +/- 56 mmHg (p < 0.01) with NO + ALM (p < 0.05 vs NO alone). Seven patients were considered as "NO-responders" (rise in PaO2/FIO2 ratio of 10 mmHg or more with NO); in this subgroup the PaO2/FIO2 ratio rose from 87 +/- 30 to 128 +/- 39 mmHg (p < 0.05) with NO alone, and from 93 +/- 20 to 169 +/- 51 mmHg (p < 0.01) with NO + ALM (p < 0.05 versus NO alone). MPAP decreased from 30 +/- 5 to 26 +/- 5 mmHg (p < 0.01) with NO alone, increased slightly from 28 +/- 5 to 31 +/- 5 mmHg (NS) with ALM alone and decreased to 27 +/- 5 mmHg (p < 0.05) with NO + ALM. CONCLUSIONS: NO + ALM had additive effects on gas exchange while decreasing MPAP in patients with ARDS. The effects of NO alone were small and non significant, except in a subgroup of 7 patients in whom the combination of both therapies had the more pronounced results.

Administration, Inhalation↗

[Tracheal intubation in patients with cervical spine injuries using a fiber optic laryngoscope].

Eleven patients, with a cervical spine injury and scheduled for elective cervical spine fusion at least 48 h after their initial trauma, were intubated using a new fiberoptic laryngoscope (Bullard). This technique uses either a semi-rigid guide independent of the laryngoscope blade, or a rigid one attached to the blade. The cervical spine was immobilized with either a collar or a halo. General anaesthesia was carried out with thiopentone, fentanyl and vecuronium bromide. Orotracheal intubation was successful at the first attempts in 10 out of the 11 patients. No mobilization of the cervical spine occurred. In the first six patients, the semi-rigid guide was used, and the rigid one in the remaining five. The anaesthetist who carried out the intubations was always the same. Using the rigid guide was easier than the semi-rigid one. This is confirmed by the time required, 44 +/- 22 sec for the rigid guide, and 97 +/- 92 sec for the semi-rigid one. In the patient in whom this technique failed at the first attempt, endotracheal intubation was carried out by the nasal route and controlled by the fiberoptic laryngoscope. This technique enables a rapid and easy orotracheal intubation in trauma patients with an immobilized cervical spine, but careful training is necessary.

Adolescent↗