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Biomedical subjects

E Legrand

Publications and source records attributed to E Legrand.

At least 19 recordsLinked to original sources
PubMed2001

Impact of protease inhibitors on intrahepatic hepatitis C virus viral load.

During chronic hepatitis C, hepatitis C virus (HCV) load in plasma was shown to be higher in HIV-co-infected than in immunocompetent patients [1]. The reason for this increased HCV replication is not known. It may be as a result of HIV-induced immune deficiency [2], although some authors did not find any correlation with the CD4 cell count [3]. A direct interaction between HCV and HIV was also hypothesized [4]. Protease inhibitors (PI) used in highly active antiretroviral therapy (HAART) have no HCV reduction effect during the first months of treatment [5-8]. However, a decrease in HCV plasma load was recently described in patients treated with HAART for a year [9,10]. We therefore investigated the potential impact of HAART on intrahepatic HCV load.

Adult↗
PubMed2001

Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules.

Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.

Antineoplastic Agents↗
PubMed2001

Fractal dimension of trabecular bone: comparison of three histomorphometric computed techniques for measuring the architectural two-dimensional complexity.

Trabecular bone has been reported as having two-dimensional (2-D) fractal characteristics at the histological level, a finding correlated with biomechanical properties. However, several fractal dimensions (D) are known and computational ways to obtain them vary considerably. This study compared three algorithms on the same series of bone biopsies, to obtain the Kolmogorov, Minkowski-Bouligand, and mass-radius fractal dimensions. The relationships with histomorphometric descriptors of the 2-D trabecular architecture were investigated. Bone biopsies were obtained from 148 osteoporotic male patients. Bone volume (BV/TV), trabecular characteristics (Tb.N, Tb.Sp, Tb.Th), strut analysis, star volumes (marrow spaces and trabeculae), inter-connectivity index, and Euler-Poincaré number were computed. The box-counting method was used to obtain the Kolmogorov dimension (D(k)), the dilatation method for the Minkowski-Bouligand dimension (D(MB)), and the sandbox for the mass-radius dimension (D(MR)) and lacunarity (L). Logarithmic relationships were observed between BV/TV and the fractal dimensions. The best correlation was obtained with D(MR) and the lowest with D(MB). Lacunarity was correlated with descriptors of the marrow cavities (ICI, star volume, Tb.Sp). Linear relationships were observed among the three fractal techniques which appeared highly correlated. A cluster analysis of all histomorphometric parameters provided a tree with three groups of descriptors: for trabeculae (Tb.Th, strut); for marrow cavities (Euler, ICI, Tb.Sp, star volume, L); and for the complexity of the network (Tb.N and the three D's). A sole fractal dimension cannot be used instead of the classic 2-D descriptors of architecture; D rather reflects the complexity of branching trabeculae. Computation time is also an important determinant when choosing one of these methods.

Cluster Analysis↗
PubMed2001

Bone microarchitecture and bone fragility in men: DXA and histomorphometry in humans and in the orchidectomized rat model.

In men, the risk of fragility fractures increases as bone mineral declines but there is an overlap in the bone mineral density (BMD) measurements between patients with and those without fractures. Biomechanical competence of trabecular (Tb) bone depends on the amount of bone and on microarchitecture. We have developed new histomorphometric methods for evaluating microarchitecture on histological sections. These methods were used in the orchidectomized male rat (ORX--a model of hypogonadism-induced osteoporosis) and on transiliac bone biopsies performed in male osteoporotic patients. ORX rats were studied at 2, 4, 8, and 16 weeks post-ORX. Bone mineral content (BMC) was reduced at 16 weeks. Trabecular bone volume (BV/TV) was significantly decreased from the 4th week. Differences in the sensitivity of the methods were found. Fractal dimension was modified as early as 2 weeks and appeared the most potent descriptor of Tb disorganization. The architectural changes in this model mimic those observed in hypogonadic men. We examined the relationships among BMD, micro-architecture, and vertebral fracture in 108 men with lumbar osteopenia (T-score <-2.5). At least one vertebral fracture was observed in 62 patients and none in 46 patients. After adjusting for age, body mass index (BMI), and BMD, there was no significant difference between the two groups in BV/TV, Tb.Th, and Star volume. In contrast, the mean values of ICI and Tb.Sp were significantly higher whereas Tb.N and nodes were lower in patients with vertebral fracture. Logistic regression analysis showed that ICI, strut analysis, and Tb.N were significant predictors of the presence of vertebral fracture: odds ratios for an alteration of I SD ranged from 1.7 for nodes to 3.2 for ICI. These results strongly suggest that bone Tb microarchitecture is a major and independent determinant of vertebral fracture in men with osteoporosis.

Absorptiometry, Photon↗
PubMed2001

Mycobacterium tuberculosis phylogeny reconstruction based on combined numerical analysis with IS1081, IS6110, VNTR, and DR-based spoligotyping suggests the existence of two new phylogeographical clades.

This paper deals with phylogenetic relationships among a set of 90 clinical strains representative of the worldwide diversity of the Mycobacterium tuberculosis complex (Kremer et al. 1999) using eight independent genetic markers: IS6110, IS1081, the direct repeat (DR) locus, and five variable number of tandem DNA repeat loci (VNTR). In a preliminary experiment, phylogenetic trees based on single markers were constructed that led to the detection of some similarities between the VNTR-based and the spoligotyping-based phylogenetic trees. In the second step, a more global phenetic approach based on pairwise comparison of strains within each typing system was used, followed by calculations of mean genetic distances based on all the eight loci and the use of the neighbor-joining algorithm for tree reconstruction. This analysis confirmed our preliminary observations and suggested the existence of at least two new phylogeographical clades of M. tuberculosis, one defined as the "East African-Indian family" (EA-I), which may find its origin on the African or Asian continents, and the other as the "Latin American and Mediterranean" (LA-M) family. The existence of these two families was also validated by an independent phylogenetic analysis of spoligotyping on a larger set of shared types (n = 252) and further corroborated by VNTR and katG-gyrA results. The potential origin of these families of bacilli is discussed based on cattle domestication and human migration history. In conclusion, the information contained in insertion sequence and repetitive DNAs may serve as a model for the phylogenetic reconstruction of the M. tuberculosis complex.

Animals↗
PubMed2001

Management of nontuberculous infectious discitis. treatments used in 110 patients admitted to 12 teaching hospitals in France.

The optimal management of pyogenic discitis is not agreed on. No randomized clinical trials of short-course or oral antibiotic regimens have been published to date. To shed light on this issue, we reviewed the management of patients admitted for pyogenic discitis to one of 12 networked rheumatology departments. In this cross-sectional observational study, each department included the first ten patients admitted starting in January 1997 for treatment of pyogenic discitis. One hundred ten patients met the inclusion criteria, 67 men and 43 women, with a mean age of 60.6 +/- 13.7 years (range, 17-86 years). Mean time from symptom onset to diagnosis was 39.6 +/- 39.8 days (range, 24 h-240 days). Blood cultures were positive in 47.3% of patients, and the percutaneous discal and vertebral biopsy in 63.6% of cases; these two investigations identified the causative organism in 79 cases (72.8%). Mean duration of the rheumatology department stay was 31.3 +/- 14.1 days (range, 4-78 days). Antibiotics were given intravenously to 103 (93.6%) patients, for a mean of 25.5 +/- 17.6 days (range, 4-124 days); duration of intravenous antibiotic therapy was longer than 4 weeks in 36.5% of patients. Only seven (6.4%) patients received primary oral antibiotics with no parenteral antibiotics. One hundred patients were given oral antibiotics at the same time as and after intravenous antibiotics, for a mean duration of 87.2 +/- 43.6 day (range, 20-278 days); Bracing was used in 98 (89.1%) patients. Although antibiotic selection was rational and in agreement with current recommendations, wide differences were noted across centers regarding intravenous treatment duration, hospital stay duration, and total treatment duration.

Abscess↗
PubMed2001

Texture analysis of X-ray radiographs is a more reliable descriptor of bone loss than mineral content in a rat model of localized disuse induced by the Clostridium botulinum toxin.

Botulism is a generalized paralyzing disease caused by the toxin of Clostridium botulinum (BTX). The toxin acts 3-4 days after injection by blocking the release of acetylcholine to the muscle. Six Wistar rats received a 2-U injection of BTX in the right quadriceps. Six rats were similarly injected with saline and were used as control. Paralysis of the quadriceps was obtained 4-5 days after the injection. Animals were killed 4 weeks after the BTX injection. The bone mineral content (BMC) was measured by dual-energy X-ray absorptiometry (DXA) on the femur and tibia. No side-to-side difference was observed for BMC on the whole tibia and femur in the BTX group. When subregions were selected in the bones, a significant decrease in BMC was obtained on the proximal tibia (-17.4 +/- 2.5%, p < 0.02). No significant difference could be observed on the proximal or distal femur, nor on the diaphyseal shafts. Numeric X-rays were done and a region of interest was transferred to an image analyzer. The texture of the trabecular bone was analyzed by the run length and fractal methods (skyscrapers and blanket). Significant differences were obtained on the proximal tibia for all methods except with fractal skyscrapers. On the distal femur, significant differences were obtained with the run length method, and the skyscrapers and the blanket method in the vertical direction. No differences were obtained with any method on the tibia and femur from control animals. Bone is a highly anisotropic material and its architecture at the microscopic level is conditioned by strains. The trabecular pattern differs in the proximal tibia than in the distal femural. Depending on the trabecular anisotropy, the algorithms can be more or less pertinent. BTX induced a significant bone loss on the bony subparts that are directly influenced by disuse. Texture analysis of X-ray images can reveal differences that were not evidenced by naked eyes. However, a combination of several methods appears necessary to appreciate the bone loss.

Absorptiometry, Photon↗
PubMed2001

Osteoporosis in men: a potential role for the sex hormone binding globulin.

The exact mechanism of bone loss remains unknown in primary male osteoporosis. It has been suggested that estrogen and sex hormone binding globulin (SHBG) play a role in regulating bone turnover and bone mass in healthy men > 65 years of age. In the present study, 80 men (mean age 49.7 years) with bone mineral density >2.5 SD below the young adult value and 40 age-matched controls were recruited to evaluate the relationships between sex hormone levels, bone biochemical markers levels, and bone mineral density. Fasting serum samples were assayed for total and free testosterone total estradiol, and SHBG. The free androgen index, was calculated as: [total testosterone/SHBG * 100]. Bone remodeling was evaluated by measurement of urinary levels of the C-telopeptide of type I collagen (CTx) and free deoxypyridinoline (D-Pyr), serum osteocalcin, and bone-specific alkaline phosphatase (bSAP). There was no significant difference between controls and osteoporotic men according to age, body mass index (BMI), total testosterone, and estradiol. In contrast, serum SHBG level was significantly higher (+42.2%), whereas free androgen index was lower (-24.8%) in patients with primary or secondary osteoporosis. Testosterone and estradiol levels did not correlate with any bone resorption or bone formation markers. In contrast, stepwise linear regression analysis showed that SHBG was significantly correlated with D-Pyr (r = 0.45, p < 0.05) and CTx (r = 0.34, p < 0.05) in primary osteoporosis. In secondary osteoporosis, SHBG was correlated with D-Pyr (r = 0.48, p < 0.05) and bSAP (r = 0.55, p < 0.01). After adjustment for age and BMI, hip bone mineral density (BMD) was not associated with testosterone or estradiol but only with serum SHBG (r = -0.33, p < 0.01) in primary osteoporosis. The same relationship was observed in men with secondary osteoporosis (r = -0.34, p < 0.01). Among osteoporotic patients, spinal radiography showed at least one vertebral crush fracture in 36 men and none in 44. Serum SHBG concentration was significantly associated with the presence of vertebral fracture: the odds ratio was 2.0 (95% confidence interval [CI] 1.2-3.5) for an increase of one standard deviation of SHBG. In conclusion, the present study showed that serum SHBG concentration is increased in middle-aged men with primary or secondary osteoporosis and is correlated with bone remodeling markers, hip bone mineral density, and vertebral fracture risk.

Adult↗
PubMed2001

Rapid differentiation of "Mycobacterium canettii" from other Mycobacterium tuberculosis complex organisms by PCR-restriction analysis of the hsp65 gene.

A total of 102 isolates of the Mycobacterium tuberculosis complex, including available "M. canettii" isolates, were studied by PCR-restriction analysis of a 441-bp fragment of the hsp65 gene. PRA upon HhaI enzyme digestion (GCGC) allowed easy differentiation of "M. canettii" from other members of the M. tuberculosis complex (three bands of 260, 105, and 60 bp for "M. canetti," compared to four bands of 185, 105, 75, and 60 bp for other members of the M. tuberculosis complex). Sequencing of the 441-bp hsp65 fragment of "M. canettii" isolates showed the disappearance of an HhaI site at position 235 due to a C-to-T transition that corresponded to position 631 of the homologous hsp65 gene of M. tuberculosis H37Rv. Considering that "M. canettii" may also exist as a stable rough morphotype, we suggest that the true number of "M. canettii" isolates may be underestimated in clinical microbiology laboratories.

Bacterial Proteins↗
PubMed2001

Use of spoligotyping to study the evolution of the direct repeat locus by IS6110 transposition in Mycobacterium tuberculosis.

Based on the variability of 43 spacers within the direct repeat (DR) locus of Mycobacterium tuberculosis complex organisms, spoligotyping is a rapid method that aids in the study of the epidemiology of tuberculosis. It was recently hypothesized that despite its presence in the DR locus, spacer 31 could not be amplified in M. tuberculosis clinical isolates belonging to spoligotype 50 due to the insertion of an extra copy of IS6110 between spacers 31 and 32 that could lead to an asymmetrical split of the primer targets (I. Filliol, C. Sola, and N. Rastogi, J. Clin. Microbiol. 38:1231--1234, 2000). In the present investigation, previous observations were extended to 25 clinical isolates of type 50 showing that the primer set IS6-DRb that selectively amplified the left and central DR regions was indeed able to demonstrate the presence of spacer 31. IS6110-restriction fragment length polymorphism (RFLP) and DR-RFLP showed that type 50 isolates were characterized by the presence of two copies of IS6110 associated with the DR locus and an additional double IS6110 band of 1.4 kb. The primer set IS3-IS6 was then used to selectively amplify a 750-bp inter-IS6110 fragment within the DR locus. The sequencing of the central DR region corroborated our previous findings and showed that the absence of spacer 31 among the type 50 isolates was due to the asymmetric insertion of an extra copy of IS6110 between spacers 31 and 32, leading to an unequal split of the DRa-DRb target into two portions, of 6 and 30 bp, respectively. These results show that the DR locus constitutes an ideal IS6110 preferential locus (ipl), permitting the insertion of two or more copies of IS6110, and provide new clues for epidemiological and phylogenetic interpretation of changes in IS6110-RFLP and spoligotyping profiles.

Bacterial Typing Techniques↗
PubMed2001

The mycobacteria: an introduction to nomenclature and pathogenesis.

Tuberculosis, caused by Mycobacterium tuberculosis, and leprosy, caused by M. leprae, are diseases known since antiquity. In developing countries, tuberculosis is still the leading cause of mortality due to an infectious disease. Taxonomically, mycobacteria belong to the genus Mycobacterium, which is the single genus within the family of Mycobacteriaceae, in the order Actinomycetales. Actinomycetales include diverse micro-organisms, but mycobacteria and allied taxa are easily distinguished on the basis of the ability to synthesise mycolic acids. Mycobacterial species are traditionally differentiated on the basis of phenotypic characteristics, and the authors provide an updated list of the biochemical tests currently employed and the culture properties that help to discriminate among various species of mycobacteria. However, as the phenotypic characteristics do not allow precise identification of all species, recent molecular taxonomical approaches for mycobacterial classification and phylogeny are also described. Mycobacteria are also a leading cause of infection in various domesticated animals and wildlife. The authors briefly describe the mycobacteria involved in animal infections, the wildlife reservoirs and strategies to control bovine tuberculosis, and the use of molecular tools for diagnostics and epidemiology of mycobacterial infections in animals. The characteristic of intracellular parasitism is discussed, in addition to the fate of pathogenic mycobacteria that have the ability to grow inside phagosomes and phagolysosomes of infected host macrophages. The mycobacterial cell envelope, which is a complex tripartite structure containing a high proportion of lipids (approximately 30% to 40% of the total weight) could play a crucial role in the adaptation of mycobacteria to intracellular growth and survival, immune modulation and drug resistance.

Animals↗
PubMed2000

SDF-1 activity on microvascular endothelial cells: consequences on angiogenesis in in vitro and in vivo models.

The chemokine stromal cell-derived factor-1 (SDF-1) has been shown to be involved in cell migration. As the receptor CXCR-4 is expressed on endothelial cells and upregulated by angiogenic factors, we were prompted to study the effect of SDF-1 on angiogenesis in endothelial cells from microvasculature. This study demonstrates that SDF-1 induces an angiogenic effect in vitro, primarily in a tridimensional fibrin gel. The increase in capillary tube formation was evident after a 10-day incubation with SDF-1. This was associated with a mild increase in VEGF production by microvascular endothelial cells (ELISA and rt-PCR) and a potent chemotactic effect. SDF-1 also induced an in vivo angiogenic activity as shown in the model of the rabbit corneal pocket. However, the angiogenesis was located in an area rich in inflammatory cells. The results of our study suggest that these data underline the potential role of SDF-1 in angiogenesis as the microvascular endothelial cells were greatly involved in this process.

Animals↗
PubMed2000

Description of a novel Mycobacterium simiae allelic variant isolated from Caribbean AIDS patients by PCR-restriction enzyme analysis and sequencing of hsp65 gene.

A sudden upsurge in the isolation of Mycobacterium simiae from terminally ill AIDS patients was recently reported on the Caribbean island of Guadeloupe. Identification of these M. simiae isolates was achieved using biochemical tests and further confirmed by PCR-restriction analysis (PRA) of a 439-bp fragment of hsp65. A novel PRA profile III (three Bst EII fragments of 240/125/80 bp and four Hae III fragments of 145/125/40/25 bp) was observed in four blood isolates from two patients. The 16 S rRNA gene sequencing of the hypervariable A region confirmed that all the pattern III isolates were indeed M. simiae species, and the hsp65 sequencing confirmed the existence of a new hsp65 allele in these caribbean isolates. A hsp65 sequence-based phylogenetic tree was also created for 39 species including M. simiae and related mycobacterial species as well as other rapid and slow growing mycobacteria, and may serve as an useful tool for identification of mycobacteria to species level.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Genetic diversity of mycobacterium avium recovered from AIDS patients in the caribbean as studied by a consensus IS1245-RFLP method and pulsed-field gel electrophoresis.

A total of 45 strains of Mycobacterium avium from 31 human immunodeficiency virus (HIV)-positive patients in the French Caribbean islands and Guiana were subjected to DNA fingerprinting using a recently described consensus IS1245 restriction fragment length polymorphism (RFLP) method, and pulsed-field gel electrophoresis (PFGE). The IS1245-RFLP resulted in three distinct clusters composed of three 27-banded isolates from two patients (cluster A), nine two-banded isolates from six patients (cluster B), and three 20-banded isolates from three patients (cluster C). PFGE results obtained after XbaI and DraI digestions gave similar clustering results irrespective of the enzyme used, and confirmed the molecular clonality for high IS1245 copy number isolates (clusters A and C). However, PFGE further discriminated the low IS1245 copy number cluster B into two distinct subclusters: subcluster I containing six isolates from four patients during the same time period from a single hospital in Guadeloupe, and subcluster IV composed of four isolates from two patients, out of which three isolates were from a single patient (patient 19). Interestingly, in the latter case, PFGE grouped together all three isolates from patient 19 despite the fact that IS1245 fingerprinting permitted grouping only two of the three isolates (the remaining unclustered isolate contained two additional bands of 3.5 and 5 kbp, and was initially considered as evidence of polyclonal infection). A combined numerical analysis of the IS1245-RFLP and PFGE results corroborated the existence of four instead of three clusters. A comparison of IS1245-RFLP versus PFGE results suggested that the standardized RFLP procedure is compatible with PFGE only for M. avium isolates containing > or = 5 copies of IS1245. Consequently, the typing results for low IS1245 copy number isolates (31% of isolates in this study) should be reconsidered for secondary typing using PFGE. Lastly, the absence of a predominant genotype of M. avium infecting HIV-positive patients over a 5-year period in this tropical region argues in favor of a lack of a privileged ecological niche for M. avium, and instead suggests that microepidemics of M. avium may prevail during limited periods of time.

AIDS-Related Opportunistic Infections↗
PubMed2000

Hypercalciuria.

Hypercalciuria is a biological syndrome defined as excretion in the urine of more than 0.1 mmol/kg/24 hours of calcium in the absence of dietary manipulation. A number of endocrine, renal, and bone diseases can cause hypercalciuria. Urinary calcium excretion is substantially influenced by dietary intakes of calcium, sodium, protein, carbohydrates, alcohol, and potassium: a poorly balanced diet can result in hypercalciuria. Recently, there has been a burst of interest in the molecular underpinnings of rare nephrolithiasis syndromes, which have been shown to result from mutations in the CLCN5 chloride channel gene. Mutations affecting the calcium-sensing receptor (CaSR) have been identified in other forms of hypercalciuria. Idiopathic hypercalciuria is defined as hypercalciuria that persists after correction of dietary imbalances and has no detectable cause. The classification suggested by Pak ("absorptive" hypercalciuria [with three types] and "renal" hypercalciuria) is controversial and of little assistance in clinical practice. Three mechanisms can be incriminated in idiopathic hypercalciuria: increased intestinal absorption of calcium, defective reabsorption of calcium by the renal tubule, and increased bone resorption. Overexpression of the vitamin D receptor (VDR) and deficiencies in renal tubule enzymes may also be involved. Bone mineral density is moderately decreased in idiopathic hypercalciuria, particularly in the renal type. The risk of vertebral fracture seems increased, however. Overproduction of calcitriol and cytokines that stimulate bone resorption have been incriminated in the bone loss. Treatment of the cause is essential in secondary hypercalciuria (dietary advice, treatment of an underlying disease, etc.). A diet low in sodium and meat and containing no more than 800 mg of calcium per day is advocated in idiopathic hypercalciuria. Hydrochlorothiazide therapy is warranted in patients with osteopenia and an inadequate response to dietary therapy.

Calcium↗
PubMed2000

The comparative toxicity of ropivacaine and bupivacaine at equipotent doses in rats.

We compared the toxicity of systemic local anesthetics bupivacaine and ropivacaine administered at equivalent and equipotent doses. In the first experiments, 18 male Wistar rats were anesthetized with thiopental and maintained under positive controlled ventilation. Electrocardiogram, electroencephalogram, and invasive arterial blood pressure were continuously recorded. The animals were randomly assigned to receive 3 mg x kg(-1) x min(-1) bupivacaine, 3 mg x kg(-1) x min(-1) ropivacaine IV (equivalent group), or 4.5 mg x kg(-1) x min(-1) ropivacaine (equipotent group). The timing of the occurrence of local anesthetic-induced toxic events (defined as the first QRS modification, dysrhythmia, seizures, moderate and severe bradycardia and hypotension, final systole) was recorded and the dose calculated. Eighteen additional rats, treated according to the same protocol were killed at the time of moderate, severe, and final hypotension for blood sampling and plasma bupivacaine and ropivacaine concentration measurement. In a third experiment, 15 awake rats (5 per group) received IV bupivacaine or ropivacaine (same infusion as in the first experiments) until seizure. At this moment, rats were allowed to recover from local anesthetic intoxication. In the first experiment, except for the first QRS modification, all the other toxic manifestations occurred at significantly larger doses (P<0.05) in the two ropivacaine groups in comparison to the bupivacaine group. In awake rats, all the animals intoxicated by ropivacaine easily recovered. In the bupivacaine group, two animals required cardiopulmonary resuscitation before any seizure activity could be detected, and only three rats survived. We conclude that, in the model used, ropivacaine, even at an equipotent dose, is less toxic than bupivacaine.

Amides↗