PubMed Health⌕ Search

Biomedical subjects

I Murat

Publications and source records attributed to I Murat.

At least 19 recordsLinked to original sources
PubMed1992

[Evaluation of 5 years of experimental in utero surgery for the repair of diaphragmatic hernia].

The incidence of diaphragmatic hernia in he newborn is 1:2,500 to 5,000 births. An extensive American programme of foetal surgery for in utero repair of this defect has shown that the pulmonary hypoplasia was due to compression of lung tissue by the herniated organs. This process could be interrupted be repairing the diaphragmatic defect early enough in utero (before the 28th week). The results of five years of experimental surgery for in utero correction of diaphragmatic hernia are presented here. The experimental model used was the Macaca fascicularis monkey, the pregnant female of which having several gestational and endocrine characteristics similar to those of the pregnant woman. Three different experimental programmes were carried out successively. A first series including five animals was used to experiment both surgical and anaesthetic techniques; three foetuses died in utero. The second series (10 animals) was designed to find a suitable protocol for tocolysis. One female died after surgery, and seven other foetuses also died. The third group (13 animals) was the main study group. The diaphragmatic hernia was first created surgically, and then repaired. No foetus died from the surgery. One female died before giving birth, and one offspring died shortly after birth as its mother had no milk. After the encouraging results obtained with this last series of animals, the procedure was applied to human cases, with the Hospital Ethical Committee's approval. In the first case, the foetus died postoperatively as a result of the rupture of the diaphragmatic prosthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1991

Pharmacokinetics of midazolam in children: comparative study of intranasal and intravenous administration.

Twelve children 1-5 y old were randomly assigned to receive midazolam 0.2 mg.kg-1 either by the intravenous (IV) or intranasal (IN) routes. After IN administration the rapid onset of absorption was observed (tmax 12 min). After both routes of administration the half-life was similar (2.2 h IN and 2.4 h IV). After IN administration the apparent plasma clearance and volume of distribution were about twice as high as after IV administration. The results are consistent with an estimated mean bioavailability of 55%.

Administration, Intranasal↗
PubMed1991

Creatine kinase and mechanical and mitochondrial functions in hereditary and diabetic cardiomyopathies.

To determine whether the development of cardiomyopathies is associated with alterations in creatine kinase function, the functional properties of cardiac contractile apparatus and mitochondria were studied in two different models of cardiomyopathies, the Syrian hamster (hereditary dilated cardiomyopathy, strain UM-X7.1, 200 days old) and the diabetic rat (4-6 weeks after injection of streptozotocin) using ventricular skinned fibers. After Triton X-100 treatment, the hereditary cardiomyopathic fibers demonstrated decreased maximal calcium-activated tension and unchanged calcium sensitivity, whereas fibers from diabetic hearts exhibited unchanged maximal tension and increased calcium sensitivity, when compared with their respective controls. In both cases myofibrillar creatine kinase appeared unchanged. The functional properties of total tissue mitochondria were evaluated using saponin-skinned fibers. Coupling between oxidation and phosphorylation was not altered in cardiomyopathies. Respiration rate (per unit of tissue dry weight) was normal in hereditary cardiomyopathy but was considerably lower in diabetic fibers compared with control fibers. In both models of cardiomyopathies, creatine-stimulated respiration was significantly lower than in controls, thus indicating the depression of functional activity of mitochondrial creatine kinase.

Animals↗
PubMed1991

[Patient-controlled analgesia in children].

This study describes the author's initial experience with "patient controlled analgesia" (PCA) in thirty school-age children for postoperative pain relief after major orthopedic surgery. The only narcotic used was morphine administered at both continuous and PCA modes. After the first eight patients, dosage regimens were changed and satisfactory postoperative analgesia was obtained in the last 20 patients with few side-effects. Recommended dosages range between 0.1 and 0.2 mg.kg-1 for loading dose, 0.01-0.02 mg.kg-1.h-1 for continuous infusion and 0.01-0.02 mg.kg-1 for PCA dose. Interest and limits of this method in children are discussed.

Adolescent↗
PubMed1990

[Mechanisms of action of halogenated anesthetics on isolated cardiac muscle].

The mechanisms responsible for the direct negative inotropic effects of the three currently used volatile anesthetics (halothane, enflurane and isoflurane) are reviewed. These agents interfere at each step of excitation-contraction coupling, i.e. sarcolemmal membrane, sarcoplasmic reticulum and contractile proteins. At the myofilament level, they decrease both calcium sensitivity and maximal developed force of cardiac skinned fibers of various species, a preparation in which all functional membranes are destroyed and thus allowing to study the direct effects of volatile anesthetics on myocardial contractile proteins. The effects of the three volatile anesthetics are similar at equipotent concentrations. The site of action seems to involve the regulatory proteins of the thin myofilament, especially troponin-tropomyosin complex. At the sarcolemmal level, all three anesthetics decrease Ca++ entry through the voltage-dependent calcium channels, an effect that seems slightly more important for both halothane and enflurane than for isoflurane. However, these two sites of action (contractile proteins and sarcolemmal membrane) are not sufficient to explain their overall negative inotropic effect. The third site of action involves the sarcoplasmic reticulum. Halothane and enflurane produce an initial liberation of Ca++ from internal stores, while isoflurane does not. All three agents decrease the net uptake of Ca++ and increase the permeability of sarcoplasmic reticulum to Ca++, similar to the effect of caffeine. However, the resulting effect, i.e. a reduction of sarcoplasmic reticulum Ca++ content occurs at clinical concentrations of halothane or enflurane, while much higher concentrations of isoflurane are required to produce a similar reduction. This differential effect on the sarcoplasmic reticulum function (which is quantitative but not qualitative) seems to be mainly responsible for the lesser negative inotropic effect of isoflurane as observed in intact cardiac muscles of various species including humans. The knowledge of the mechanisms of action of volatile anesthetics is important for understanding the potential consequences associated with their use in patients receiving cardiac drugs, especially calcium blockers and phosphodiesterase inhibitors.

Animals↗
PubMed1990

Effects of volatile anesthetics on mechanical properties of rat cardiac skinned fibers.

Volatile anesthetics were demonstrated to decrease calcium sensitivity and maximal developed force of detergent-treated rat cardiac skinned fibers. To further investigate the possible mechanisms involved in the decrease of force production, stiffness measurements were performed at defined levels of activation with the use of quick length changes of 0.3 to 4% of initial muscle length in the absence and in the presence of 2 MAC of halothane, enflurane, or isoflurane. The results of various series of experiments suggest that these anesthetics have multiple sites of action on cardiac myofibrillar proteins: 1) they decreased active stiffness indicating a decreased number of attached force-generating cross-bridges; 2) they increased the stiffness/force ratio suggesting that the individual force developed by each cross-bridge was decreased during anesthetic exposure; and 3) they increased the time constant of force recovery, which is consistent with the decreased rate of ATP hydrolysis described by others. These changes in cross-bridges kinetics and efficiency may result from conformational changes in all the protein systems involved in force production, and especially actin-myosin attachment and detachment. However, the changes observed were small despite a relatively high concentration of anesthetics; therefore, they will probably participate only to a moderate extent in the overall negative inotropic effect of these agents.

Animals↗
PubMed1990

Developmental changes in effects of halothane and isoflurane on contractile properties of rabbit cardiac skinned fibers.

Immature hearts of various animal species and humans have been demonstrated to be more sensitive than adult hearts to the myocardial depressant effects of volatile anesthetics. To further investigate the mechanisms involved, the calcium sensitivity and maximal activated tension of detergent-treated left ventricular fibres of fetuses (30 days), newborn (1-day-old), immature (3-, 8-, and 17-day-old), and adult rabbits were determined by stepwise exposure to increasing Ca2+ concentrations. Responses were measured prior to and after exposure to equianesthetic concentrations of halothane (1%) or isoflurane (1.5%) applied in a random order. In control conditions maximal developed tension was the lowest in fetuses (11.1 +/- 0.6 mN.mm-2), intermediate in newborn and immature rabbits, and highest in adults (25.6 +/- 2.9 mN.mm-2). There were also age-related changes in calcium sensitivity; pCa (= -log10[Ca2+]) for half-activation (pCa50) was significantly less in 1-, 3-, and 8-day-old rabbits (5.444 +/- 0.036, 5.425 +/- 0.017, and 5.385 +/- 0.019, respectively) than in adults (5.517 +/- 0.010), whereas it was not different in fetuses (5.521 +/- 0.017). During anesthetic exposure both calcium sensitivity and maximal developed tension decreased significantly in all age groups of animals, with both anesthetics having a similar effect in animals of identical age. However, calcium sensitivity decreased significantly more in newborn animals (0.192 and 0.196 pCa unit for halothane and isoflurane, respectively) compared with adults (0.122 and 0.137 pCa units, respectively). By contrast, fetuses were less sensitive to the myocardial depressant effects of anesthetics than were newborn animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1990

Rectal flunitrazepam as premedication in preschool children. A double-blind randomized study.

The efficacy of flunitrazepam (0.04 mg.kg-1) as a premedicant was evaluated in 40 young children of less than 5 years of age in a double-blind, placebo-controlled study. Flunitrazepam was given by the rectal route 15 min prior to an inhalational mask induction with halothane. Sedation score, mask acceptance and induction score were significantly better in premedicated children than in the placebo group. There were no hypoxic episodes, prolonged sedation or other complications in either group. This suggests that flunitrazepam administered rectally in a low dose is an acceptable premedication in young children.

Administration, Rectal↗
PubMed1990

The use of midazolam in diagnostic and short surgical procedures in children.

A new technique of sedation for children is described, in which midazolam (0.2 mg.kg-1) was administered topically by the nasal route, followed by ketamine (9.0 mg.kg-1) administered rectally in 32 patients breathing air spontaneously. Sedation was good in 23, seven required further ketamine (1.0 mg.kg-1 i.v.), and in two, halothane was introduced. There was no evidence of severe respiratory depression except during oesophagoscopy. Cardiovascular stability was excellent. Of 21 patients over 5 years old, 19 developed complete and two partial anterograde amnesia for the administration of ketamine and surgery. The major complications were nausea and vomiting (five patients) and salivation (eight patients). The mean recovery time was 40 min (s.d. 33 min). It provided a relatively safe, adaptable, non-invasive method of inducing sedation in children.

Administration, Intranasal↗
PubMed1989

Effects of halothane on contractile properties of skinned fibers from cardiomyopathic animals.

The effects of clinical concentrations of halothane (1 and 2% v/v) on detergent treated cardiac fibers were studied in two different models of cardiomyopathic animals, the Syrian hamster UM-X7.1, and the streptozotocin-induced diabetic rat. The changes of contractile properties in cardiac muscle observed on cardiomyopathic animals, although of moderate importance, were different in these two models. The cardiomyopathic hamsters exhibited macroscopic structural changes in cardiac muscle responsible for a significant decrease in maximal activated tension, but myocardial calcium sensitivity was unchanged. On the other hand, in diabetic rats, maximal activated tension was unchanged, while a slight but significant increase in myocardial calcium sensitivity was observed. Addition of halothane produced a similar dose-dependent decrease in myocardial calcium sensitivity, in both the controls and the two groups of cardiomyopathic animals. Halothane exposure was also associated with a dose-dependent decrease in maximal calcium activated tension in all groups, an effect that was more pronounced in cardiomyopathic hamsters than in their control at the lowest anesthetic concentration. These results indicate that the negative inotropic effects of halothane are additive to the myocardial depression observed in these cardiomyopathies.

Animals↗
PubMed1989

[Hormonal changes induced by etomidate in children during the first 24 postoperative hours].

The hormonal effects of an etomidate infusion were assessed postoperatively in children undergoing hypospadias or clubfoot repair. The study was carried out in 12 children, aged between 9 and 70 months, randomly assigned to two equal groups. The anaesthetic protocol was identical for all the children, consisting in a light general anaesthesia (halothane induction, intubation after 60 to 80 micrograms.kg-1 vecuronium) combined with lumbar epidural anaesthesia (initial dose of 0.75 ml.kg-1 bupivacaine with adrenaline, with repeat injections of half the previous dose when there was a change in the haemodynamic parameters suggesting inadequate analgesia). Anaesthetic maintenance was different in both groups: 1 to 1.5 vol% enflurane in a nitrous oxide-oxygen mixture (1/1 v/v) in the control group, and 16.8 +/- 3.0 mg.kg-1.min-1 etomidate infusion in the etomidate group. Venous blood samples were collected after induction of anesthesia (before starting the epidural anaesthesia and the etomidate infusion), at the end of surgery (H0), at the 3rd (H3), 6th (H6), 12th (H12) and 24th h (H24) following surgery. The following hormonal blood concentrations were measured: cortisol, 11 beta-desoxycortisol, aldosterone, 11 beta-desoxycorticosterone, dehydroepiandrosterone (DHA) and DHA sulphate (DHA-S). In the control group, cortisol and DHA-S concentrations decreased significantly at H0, aldosterone levels also being significantly lower at H24. In the etomidate group, cortisol concentrations remained significantly lower at H0, H3 and H6; aldosterone concentrations were also significantly lower than control values throughout the study period. There was an important prolonged rise in the concentrations of their precursors. DHA and DHA-S concentrations did not change in the etomidate group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1989

Isoflurane attenuates baroreflex control of heart rate in human neonates.

Clinical studies have suggested that baroreflex regulation of heart rate may be more affected by inhalational anesthetics in human neonates or young animals than in adults. To test this hypothesis, baroreceptor reflex control of heart rate was studied in eight neonates during administration of 1 MAC isoflurane. The neonates were hemodynamically stable and their lungs were mechanically ventilated. No other anesthetic was used. Mean (+/- SD) corrected gestational age was 39.4 +/- 2.0 weeks and mean weight was 2,710 +/- 430 g. The pressor response was tested with the use of phenylephrine and the depressor response with nitroglycerin. Changes in heart rate (R-R interval) were plotted against the changes in systolic arterial pressure, and the slope of the linear portion of this relationship was used to define the baroreflex response. Both baroresponses measured in awake neonates varied widely between patients. With administration of approximately 1 MAC isoflurane, the pretest mean systolic arterial pressure decreased by about 30% (P less than 0.001), whereas mean heart rate values remained unchanged compared with control awake values. During isoflurane administration, the mean (+/- SD) pressor response decreased to 23% of control awake values (11.2 +/- 7.7 ms/mmHg vs. 2.6 +/- 3.7 ms/mmHg; P less than 0.01) and the depressor response to 28% of control (4.3 +/- 3.2 ms/mmHg vs. 1.2 +/- 0.8 ms/mmHg; P less than 0.05). These changes can be attributed to a significant resetting of heart rate itself (calculated as the change in R-R interval at a constant pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗