Bouguer anomaly inversion and hydrocode modeling of the central uplift of the Araguainha impact structure.

Araguainha is a mid-sized complex impact structure formed in sedimentary and underlying basement rocks of the Paraná Basin, Brazil. The structure has strongly deformed sedimentary strata surrounding a granitic core. The central uplift is a region of high geological complexity, comprising different types of sedimentary, igneous (granite) and metamorphic lithologies, plus breccias and impact melt sheets. New ground gravity data was collected to produce a Bouguer anomaly map and to perform a 3-D inversion in order to obtain a 3-D density model of the central uplift. This 3-D density model is consistent with iSALE numerical modeling results, which shows that the rocks in the innermost portion became brecciated and/or melted after undergoing pressure/temperature peaks. The positive anomaly of Furnas and Ponta Grossa formations associated with the numerical model shows that the central uplift is ~16 km wide. Thus, the granite's uplift caused the uplift of the entire stratigraphic package, from its Devonian-aged units to the Permian ones, forming a bull's eye pattern around the granitic core. The results also indicate that Araguainha was formed by a 3 km diameter impactor, and the rocks of the granitic basement rocks were uplifted by ~2 km.

Correction: Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

[This corrects the article DOI: 10.1371/journal.pone.0173715.].

Hypervirulent Mycobacterium tuberculosis strain triggers necrotic lung pathology associated with enhanced recruitment of neutrophils in resistant C57BL/6 mice.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. The murine model of TB in resistant C57BL/6 mice infected with reference Mtb strains is widely used in TB studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. Recently, we demonstrated that necrotic lung lesions could be induced in the C57BL/6 mice by highly virulent Mtb strains belonging to the modern Beijing sublineage. However, the pathogenic mechanisms leading to necrosis in this model were not elucidated. In this study, we investigated the dynamics of lung lesions in mice infected with highly virulent Beijing Mtb strain M299, compared with those infected with laboratory Mtb strain H37Rv. The data demonstrate that necrotic lung lesions in mice infected by the strain M299 were associated with enhanced recruitment of myeloid cells, especially neutrophils, and increased levels of proinflammatory cytokines, consistent with exacerbated inflammation. High levels of IFN-γ production contributed to the control of bacterial growth. Further progression to chronic disease was associated with a reduction in the levels of inflammatory mediators in the lungs, the accumulation of foamy macrophages and partial healing of the necrotic tissue by fibrosis. At a late stage of disease, degradation of foamy cells resulted in the liberation of accumulated lipids and persisting bacilli and further activation of inflammation, which promoted lung consolidation. Overall, our studies show that C57BL/6 mice infected with highly virulent Mtb strain may serve as a TB model reproducing an exacerbated inflammatory response in a resistant host to hypervirulent mycobacteria, leading to irreversible necrotic lung lesions.

Pulmonary infection with hypervirulent Mycobacteria reveals a crucial role for the P2X7 receptor in aggressive forms of tuberculosis.

The purinergic P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine production and cell death. To investigate whether the innate immune response to damage signals could contribute to the development of pulmonary necrotic lesions in severe forms of tuberculosis, disease progression was examined in C57BL/6 and P2X7R-/- mice that were intratracheally infected with highly virulent mycobacterial strains (Mycobacterium tuberculosis strain 1471 of the Beijing genotype family and Mycobacterium bovis strain MP287/03). The low-dose infection of C57BL/6 mice with bacteria of these strains caused the rapid development of extensive granulomatous pneumonia with necrotic areas, intense bacillus dissemination and anticipated animal death. In contrast, in P2X7R-/- mice, the lung pathology presented with moderate infiltrates of mononuclear leukocytes without visible signs of necrosis; the disease attenuation was accompanied by a delay in mortality. In vitro, the hypervirulent mycobacteria grew rapidly inside macrophages and induced death by a P2X7R-dependent mechanism that facilitated the release of bacilli. Furthermore, these bacteria were resistant to the protective mechanisms elicited in macrophages following extracellular ATP stimulation. Based on this study, we propose that the rapid intracellular growth of hypervirulent mycobacteria results in massive macrophage damage. The ATP released by damaged cells engages P2X7R and accelerates the necrotic death of infected macrophages and the release of bacilli. This vicious cycle exacerbates pneumonia and lung necrosis by promoting widespread cell destruction and bacillus dissemination. These findings suggest the use of drugs that have been designed to inhibit the P2X7R as a new therapeutic approach to treat the aggressive forms of tuberculosis.

Mycobacterium tuberculosis strains of the modern sublineage of the Beijing family are more likely to display increased virulence than strains of the ancient sublineage.

Strains of the Beijing genotype family of Mycobacterium tuberculosis are a cause of particular concern because of their increasing dissemination in the world and their association with drug resistance. Phylogenetically, this family includes distinct ancient and modern sublineages. The modern strains, contrary to the ancestral counterparts, demonstrated increasing prevalence in many world regions that suggest an enhanced bacterial pathogenicity. We therefore evaluated virulence of modern versus ancient Beijing strains with similar epidemiological and genotype characteristics. For this, we selected six strains that had very similar 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing profiles and belonged to the region of difference 181 (RD181) subgroup but differed using markers (mutT2 and mutT4 genes and NTF locus) that discriminate between modern and ancient Beijing sublineages. The strains were isolated from native patients in Brazil and Mozambique, countries with a low prevalence of Beijing strains. The virulence levels of these strains were determined in models of pulmonary infection in mice and in vitro macrophage infection and compared with that of a strain from Russia, part of the epidemic and hypervirulent Beijing clone B0/W148, and of the laboratory strain H37Rv. The results showed that two of the three modern Beijing strains were highly pathogenic, exhibiting levels of virulence comparable with that of the epidemic Russian strain. In contrast, all isolates of the ancient sublineage displayed intermediate or low virulence. The data obtained demonstrate that the strains of the modern Beijing sublineage are more likely to exhibit highly virulent phenotypes than ancient strains and suggest that genetic alterations characteristic of the modern Beijing sublineage favor selection of highly virulent bacteria.

Physiological responses of preterm newborn infants submitted to classical music therapy.

OBJECTIVE: To evaluate the physiological effects of music therapy on hospitalized preterm newborns. METHODS: A noncontrolled clinical trial including 12 newborn infants with gestational age <36 weeks, spontaneously breathing. The preterm infants were submitted to 15-minute sessions of classical music therapy twice a day (morning and afternoon) for three consecutive days. The variables: heart and respiratory rates, oxygen saturation, diastolic and systolic arterial pressures, and body temperature were analyzed before and immediately after each music therapy session. RESULTS: There was a decrease in the heart rate after the second session of music therapy (paired t-test; p=0.002), and an increase at the end of the third session (paired t-test; p=0.005). Respiratory rate decreased during the fourth and fifth sessions (paired t-test; p=0.01 and 0.03, respectively). Regarding oxygen saturation, there was an increase after the fifth session (p=0.008). Comparison of physiological parameters among sessions, for the six studied sessions, showed only that the gain in oxygen saturation during the fifth session was significantly higher than during the sixth one (Tukey's test after variance analysis; p=0.04). CONCLUSIONS: Music therapy may modify short-term physiological responses of hospitalized preterm newborn infants.

Toxic cardiomyopathy leading to fatal acute cardiac failure related to vandetanib: a case report with histopathological analysis.

CONTEXT: Medullary thyroid carcinoma (MTC) accounts for 3-4% of all malignant thyroid neoplasias. Vandetanib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor 2, epidermal growth factor receptor, and RET, has been approved by the FDA for the treatment of locally advanced or metastatic MTC. The heart seems to be particularly susceptible to adverse effects associated with TKI therapy, and virtually all TKIs have been associated with cardiovascular events. CLINICAL PRESENTATION: We report the case of a patient with metastatic MTC who was enrolled in the Phase III clinical study (NCT00410761) and presented a favorable response to vandetanib therapy, displaying marked decrease in the level of serologic tumor markers and shrinkage of metastatic lesions. After 14 months of therapy, the patient developed a fatal cardiac failure. Myocardial infarction was excluded by serial measurements of specific cardiac markers (serial troponin-T measurements varied from 0.037 to 0.042 ng/ml) and serologic tests for Chaga's disease were negative. Postmortem examination of the heart revealed cardiomyocyte hypertrophy and marked myocyte degeneration in the subendocardial zones and papillary muscles of the myocardium. These pathological changes are similar to those observed in TKI-treated rats and are suggestive of drug-induced cardiotoxicity. CONCLUSION: This case illustrates a previously unreported serious vandetanib-related adverse effect and highlights the need for close monitoring of patients under TKI therapy in order to identify early signs of congestive heart failure or myocardium damage.

Respostas fisiológicas de recém-nascidos pré-termo submetidos à musicoterapia clássica / Physiological responses of preterm newborn infants submitted to classical music therapy / Respuestas fisiológicas de recién nacidos pretérmino sometidos a musicoterapia clásica

OBJETIVO: Avaliar o efeito da musicoterapia nas respostas fisiológicas de recém-nascidos pré-termo hospitalizados. MÉTODOS: Ensaio clínico não controlado realizado com 12 recém-nascidos pré-termo, com idade gestacional <36 semanas, em respiração espontânea. Os pacientes foram submetidos a sessões de musicoterapia durante 15 minutos duas vezes ao dia, nos períodos matutino e vespertino, por três dias consecutivos. As variáveis: frequências cardíaca e respiratória, saturação de oxigênio, pressões arteriais sistólica e diastólica e temperatura corporal foram analisadas antes e imediatamente após a sessão de musicoterapia. RESULTADOS: Observou-se a diminuição da frequência cardíaca imediatamente após a segunda sessão de musicoterapia (t pareado; p=0,002) e o aumento ao final da terceira sessão, em relação ao início (t pareado; p=0,005). A frequência respiratória diminuiu após a musicoterapia na quarta e quinta sessões (t pareado; p=0,01 e 0,03, respectivamente). Em relação à saturação de oxigênio, houve aumento após a quinta sessão de musicoterapia (p=0,008). A análise de variância realizada entre as seis sessões, após o cálculo da média das diferenças entre os parâmetros iniciais e finais, demonstrou que o ganho médio de saturação de oxigênio na quinta sessão foi maior do que na sexta (teste de Tukey após análise de variância; p=0,04). CONCLUSÕES: A musicoterapia pode modificar em curto prazo as respostas fisiológicas de recém-nascidos pré-termo hospitalizados.

OBJECTIVE: To evaluate the physiological effects of music therapy on hospitalized preterm newborns. METHODS: A noncontrolled clinical trial including 12 newborn infants with gestational age <36 weeks, spontaneously breathing. The preterm infants were submitted to 15-minute sessions of classical music therapy twice a day (morning and afternoon) for three consecutive days. The variables: heart and respiratory rates, oxygen saturation, diastolic and systolic arterial pressures, and body temperature were analyzed before and immediately after each music therapy session. RESULTS: There was a decrease in the heart rate after the second session of music therapy (paired t-test; p=0.002), and an increase at the end of the third session (paired t-test; p=0.005). Respiratory rate decreased during the fourth and fifth sessions (paired t-test; p=0.01 and 0.03, respectively). Regarding oxygen saturation, there was an increase after the fifth session (p=0.008). Comparison of physiological parameters among sessions, for the six studied sessions, showed only that the gain in oxygen saturation during the fifth session was significantly higher than during the sixth one (Tukey's test after variance analysis; p=0.04). CONCLUSIONS: Music therapy may modify short-term physiological responses of hospitalized preterm newborn infants.

OBJETIVO: Evaluar el efecto de la musicoterapia en las respuestas fisiológicas de recién nacidos pretérmino hospitalizados. MÉTODOS: Ensayo clínico no controlado realizado con 12 recién nacidos pretérmino internados en la Unidad de Terapia Intensiva Neonatal y en la Unidad Intermediaria, con edad gestacional <36 semanas en respiración espontánea. Los recién nacidos pretérmino fueron sometidos a sesiones de musicoterapia durante 15 minutos dos veces al día, en los periodos matutino y vespertino, durante tres días consecutivos. Las variables: frecuencia cardíaca y respiratoria, saturación de oxígeno, presiones arteriales sistólica y diastólica y temperatura corporal fueron analizadas antes e inmediatamente después de la sesión de musicoterapia. RESULTADOS: Fueron observados la reducción de la frecuencia cardíaca inmediatamente después de la segunda sesión de musicoterapia (t pareado; p=0,002) y el aumento al final de la tercera sesión, respecto al inicio (t pareado; p=0,005). La frecuencia respiratoria se redujo después de la musicoterapia en la cuarta y quinta sesiones (t pareado; p=0,01 y 0,03, respectivamente). Respecto a la saturación de oxígeno, hubo aumento después de la quinta sesión de musicoterapia (p=0,008). El análisis de variancia realizado entre las seis sesiones después del cálculo del promedio de las diferencias entre los parámetros iniciales y finales demostró que la ganancia mediana de saturación de oxígeno en la quinta sesión fue más grande que en la sexta (prueba de Tukey después de análisis de variancia; p=0,04). CONCLUSIONES: La musicoterapia puede modificar en corto plazo las respuestas fisiológicas de recién nacidos pretérmino hospitalizados.

Exon 11 mutations, Ki67, and p16(INK4A) as predictors of prognosis in patients with GIST.

Prognostic biomarkers for GIST are under investigation. The aim of this study was to assess whether exon 11 mutations, Ki67, and p16(INK4A) are predictors of prognosis in GIST. Consecutive GIST cases (n=84) had their specimens evaluated for exon 11 mutations and expression of Ki67 and p16(INK4A). Surgical cases were categorized according to NIH and Miettinen's classification, and survival was analyzed from hospital database. GISTs were predominately gastric (45%) and with spindle cell morphology (74%). The risk category was very low or low in 28%, intermediate in 23%, and high in 49%. Exon 11 mutation was identified in 29 (48%) out of 60 cases studied. There were 12 point mutations, 10 deletions, 4 duplications, and 3 double mutations. A third of GISTs had either high Ki67 index (>3%) or negativity for p16(INK4A). In multivariate analysis, independent predictors of mortality were Ki67>3% (HR=7.3; P=0.036) and high mitotic index (HR=10.4; P=0.043). There was no association between exon 11 mutations and survival. This study suggests that Ki67>3% is an independent predictor of poor prognosis in patients with GIST. Exon 11 mutations and negativity for p16(INK4A) need further studies to address the prognostic value.

Emerging multidrug resistant Mycobacterium tuberculosis strains of the Beijing genotype circulating in Russia express a pattern of biological properties associated with enhanced virulence.

The epidemiologically important Mycobacterium tuberculosis Beijing genotype strains, highly endemic in East Asia, have become an emerging infection in certain geographic areas, including Russia, because of its increasing prevalence and association with multidrug resistance (MDR). The aim was to verify whether MDR Beijing strains circulating in the emerging regions present some biological particularities that could contribute to their success in causing disease in comparison with the sporadic strains from locations with low prevalence of the Beijing genotype. We evaluated virulence-associated characteristics of the MDR Beijing strains isolated in Russia and compared them with those of the drug-resistant and susceptible Beijing strains from Brazil and reference H37Rv strain. We found that Russian MDR strains demonstrated an increased bacterial fitness and growth in THP-1 macrophage-like cells, as well as a higher capacity to induce non-protective cytokine synthesis and necrotic macrophage death. By contrast, the biological properties of the strains isolated in Brazil largely resembled those of the H37Rv strain, with the exception of the drug-resistant isolates that presented significantly reduced fitness. The data demonstrate that the emerging MDR strains of the Beijing genotype circulating in Russia do express a pattern of properties associated with the enhanced virulence favouring its clonal dissemination in this region.

Emerging multidrug resistant Mycobacterium tuberculosis strains of the Beijing genotype circulating in Russia express a pattern of biological properties associated with enhanced virulence

The epidemiologically important Mycobacterium tuberculosis Beijing genotype strains, highly endemic in East Asia, have become an emerging infection in certain geographic areas, including Russia, because of its increasing prevalence and association with multidrug resistance (MDR). The aim was to verify whether MDR Beijing strains circulating in the emerging regions present some biological particularities that could contribute to their success in causing disease in comparison with the sporadic strains from locations with low prevalence of the Beijing genotype. We evaluated virulence-associated characteristics of the MDR Beijing strains isolated in Russia and compared them with those of the drug-resistant and susceptible Beijing strains from Brazil and reference H37Rv strain. We found that Russian MDR strains demonstrated an increased bacterial fitness and growth in THP-1 macrophage-like cells, as well as a higher capacity to induce non-protective cytokine synthesis and necrotic macrophage death. By contrast, the biological properties of the strains isolated in Brazil largely resembled those of the H37Rv strain, with the exception of the drug-resistant isolates that presented significantly reduced fitness. The data demonstrate that the emerging MDR strains of the Beijing genotype circulating in Russia do express a pattern of properties associated with the enhanced virulence favouring its clonal dissemination in this region.

Mycobacteria directly induce cytoskeletal rearrangements for macrophage spreading and polarization through TLR2-dependent PI3K signaling.

Macrophage migration and adhesion are important for the control of mycobacterial infection and are critically dependent on the reorganization of the cytoskeleton. Mycobacteria elicit rapid morphological changes, such as cell spreading, a process relevant to in vivo changes of macrophage shape during extravasation and migration. In this study, we investigated the BCG mycobacteria-induced signaling events leading to macrophage cytoskeletal rearrangements employing specific pharmacological inhibitors to suppress distinct kinase pathways known to be elicited by infection. Viable or lysed mycobacteria, as well as purified cell wall lipoprotein p19, TLR2 agonist, induced RAW264.7 cells to extend actin-rich pseudopods, which impart radial spreading within 3 h, leading later to persistent cell polarization. BCG induced rapid activation of phosphatidylinositol 3-kinase, PI3K, activation that was recruited to the activated TLR2 receptor. TLR2- neutralizing antibody inhibited macrophage spreading and PI3K activation induced by p19. Additionally, BCG induced spreading and polarization of bone marrow-derived macrophages from TLR2- expressing mice in contrast to their TLR2-knockout counterparts. Neither MEK1/ERK, p38 MAPK, nor NF-kappaB activation were important for the early cytoskeletal rearrangements observed, although suppression of these pathways is known to inhibit chemokine secretion by activated macrophages. Beta2-integrins blockade with a corresponding antibody inhibited macrophage spreading and polarization but had no effect on pseudopodia protrusions demonstrating the downstream position of integrin-mediated adhesion in PI3K- dependent signaling pathway leading to the motility phenotype. The obtained data demonstrate that the direct effect of mycobacteria on macrophage shape might be mediated through TLR2-dependent PI3K activation.

Mulher branca, 45 anos, consulta por diarréia crônica, emagrecimento e anemia ferropênica / 45-year-old, white woman presents with chronic diarrhea, weight loss and iron deficiency anemia

Em novembro de 1996, uma mulher branca de 45 anos veio à consulta por diarréia aquosa e emagrecimento acentuado. Negava tabagismo e alcoolismo. Ao exame físico, apresentava mucosas hipocoradas e emagrecimento. Trazia consigo o laudo de uma endoscopia digestiva alta considerada normal e de uma colonoscopia com descrição de cólon espástico. Os exames mostraram, no soro: glicose, 74 mg/dL; uréia, 13 mg/dL; creatinina, 0,4 mg/dL; sódio, 137 mEq/L; e potássio, 4,3 mEq/L. A pesquisa de leucócitos fecais e o parasitológico de fezes foram negativos (três amostras). Foi iniciado sulfato ferroso via oral. A reavaliação, em fevereiro de 1997, mostrou os exames contidos na tabela 1, além de: alanina aminotransferase (ALT), 57 UI/L (3-17); aspartato aminotransferase (AST), 62 UI/L (9-36); bilirrubinas e provas de coagulação normais. Foi iniciada a suplementação de ácido fólico. Como havia queixa de menorragia, a paciente foi avaliada por ginecologista, que indicou reposição hormonal. Em abril de 1998, a paciente persistia com queixa de menorragia e emagrecimento. Foi submetida a nova endoscopia digestiva alta, que evidenciou algumas erosões com fibrina, no antro, e mucosa de bulbo duodenal com aspecto ladrilhado

Effects of inhaled nitric oxide on pulmonary hemodynamics in a porcine model of endotoxin shock.

OBJECTIVE: To evaluate the effects of inhaled nitric oxide (NO) on pulmonary circulation in a porcine endotoxin shock model. DESIGN: Prospective, randomized trial. SETTING: Laboratory at a large university medical center. SUBJECTS: Twelve pathogen-free pigs weighing 15 to 31 kg. INTERVENTIONS: After surgical preparation, all pigs received a 0.5 mg/kg endotoxin infusion over 30 mins. One hour after the start of endotoxin, NO inhalation (40 ppm) was initiated in six pigs, whereas the six remaining pigs served to control the progression of shock in this model. Consecutive changes in systemic and pulmonary hemodynamics, including characteristic resistance, vascular compliance, peripheral vascular resistance, and inductance, were continuously assessed during the experimental protocol using a four-element Windkessel model of the pulmonary circulation. MEASUREMENTS AND MAIN RESULTS: Endotoxin insult resulted in a biphasic pulmonary artery pressure increase from 14 +/- 2 to 32 +/- 4 mm Hg. Inhaled NO reversed the resistance to blood flow in small pulmonary arteries from 596 +/- 69 to 424 +/- 36 dyne-sec/ cm5. In contrast, the vascular capacitance of the entire pulmonary circuit, which decreased from 2.4 +/- 0.2 to 0.8 +/- 0.1 mL/mm Hg throughout endotoxin challenge, remained insensitive to NO administration. CONCLUSION: In endotoxin-induced pulmonary hypertension, inhaled NO may function as a modulator of distal pulmonary arterial tone but fails to act as a regulator of larger capacitance pulmonary vessels.

Analysis of endotoxin effects on the intact pulmonary circulation.

OBJECTIVE: The mechanism of sustained alterations in pulmonary hemodynamics during endotoxin shock remains unclear. To gain more detailed knowledge we used the four-element windkessel model as a descriptor of the pulmonary circuit. METHODS: Consecutive changes in characteristic resistance (R1), vascular compliance (C), input resistance (R2) and inductance (L) were continuously assessed following injection of endotoxin in 6 anaesthetised pigs, and were compared with the corresponding values measured in a similar group of sham-operated animals. RESULTS: Endotoxin challenge resulted in a biphasic pulmonary artery pressure response. Blood flow decreased progressively from 2.8 +/- 0.2 l/min to 2 +/- 0.2 l/min. Ohmic pulmonary vascular resistance (PVR) increased gradually from 0.2 +/- 0.04 to 0.76 +/- 0.1 mm Hg s ml-1. The early increase in PAP (from 14 +/- 2 to 27 +/- 4 mm Hg) was mediated by changes in both R1 (from 0.04 +/- 0.01 to 0.06 +/- 0.01 mm Hg s ml-1) and R2 (from 0.16 +/- 0.04 to 0.61 +/- 0.2 mm Hg s ml-1). These responses, in turn, altered the proximal vascular compliance. A subsequent increase in PAP (from 27 +/- 2 to 32 +/- 3 mm Hg) paralleled the specific decline in distal pulmonary vasculature compliance from 0.84 +/- 0.1 to 0.65 +/- 0.1 ml/mmHg. Analysis of the time course of PVR did not allow us to distinguish between vasoconstriction and stiffening of the vascular tree as mechanisms accounting for PAP changes. CONCLUSIONS: Endotoxemia leads to pulmonary hypertension, which is a result of constriction of proximal pulmonary arteries during the early phase, whereas the late phase is characterised by a decline in distal pulmonary vasculature compliance.

Correction of pressure waveforms recorded by fluid-filled catheter recording systems: a new method using a transfer equation.

BACKGROUND: Pressure measuring systems using fluid-filled catheters can result in the recording of distorted pressure waveforms. It results in phase delay, overestimation of systolic and, to a lesser extent, of diastolic pressure. We designed and evaluated a method to correct this pressure waveform distortion using an appropriate transfer equation obtained from the dynamic response of the fluid-filled catheter. This transfer equation is based on the principle that a fluid-filled catheter recording system is considered as an underdamped dynamic system fully characterized by its natural frequency (omega n) and damping ratio (zeta). METHODS: Pressure waveforms, simultaneously recorded in vitro or in vivo by a fluid-filled catheter (Pc) and a micromanometer-tipped catheter (Pref), were used to validate the method. Dynamic response of the catheter used was obtained from a fastflush test. The corrected signal (Ppred) was obtained using omega n, zeta and the following transfer equation: d2Pc/dt2 + 2 omega n zeta dPc/dt + omega n 2Pc = C Ppred (t) After correction of Pc, Ppred was compared, using a linear regression, with Pref taken as reference. RESULTS: Our results showed that Ppred was fitted to Pref with excellent coefficient correlation (0.99). The mean error and the standard error of estimate were respectively -1.16 mmHg and 1.4 mmHg. CONCLUSION: This new method can convert the distorted pressure waveforms transmitted by any fluid-filled catheters into high-fidelity signals. It suppresses the phase delay and the over-estimation of systolic pressure induced by fluid-filled catheters.

Pulmonary impedance and right ventricular-vascular coupling in endotoxin shock.

OBJECTIVE: We tested the hypothesis that right heart failure during endotoxin shock may result from altered ventriculovascular coupling responsible for impeding power transfer to the pulmonary circulation. METHODS: The changes in vascular pulmonary input impedance and right ventricular contractility produced by low-dose endotoxin infusion were studied in 6 intact anesthetized dogs. RESULTS: Endotoxin insult resulted in pulmonary hypertension (from 22 +/- 2 to 33 +/- 3 mmHg) associated with significant decreases in stroke volume (from 26.9 +/- 4 to 20.2 +/- 3 ml) and right ventricular ejection fraction (from 41 +/- 3 to 32 +/- 2%). The first minimum of input impedance spectrum and zero phase were shifted towards higher frequencies. Input resistance and characteristic resistance were dramatically increased. The latter change contributed to a significant increase in the pulsatile component of total right ventricular power output from 13 to 21%, indicating a reduction in the hydraulic right ventricle power output delivered into the main pulmonary artery. Overall changes in input pulmonary impedance were indicative of increased afterload facing the right ventricle leading to depressed performance. In contrast, right ventricular systolic elastance was simultaneously increased from 0.56 to 0.93 mmHg/ml indicating an increase in right heart contractility. CONCLUSION: These data suggest that pulmonary hypertension in the setting of experimental endotoxin shock is accompanied by deleterious changes in the pulmonary impedance spectrum, which are responsible for a mismatch of increased contractile state of the right ventricle to the varying hydraulic load ultimately leading to ventricular-vascular uncoupling.

Leukotrienes antagonist-inhibitor and the bronchial response to inhaled antigen in actively sensitized guinea-pigs.

The aim of the study was to estimate an eventual contribution of leukotrienes in respiratory mechanic changes observed in guinea-pig during bronchial anaphylaxis. Twenty-eight guinea-pigs, actively sensitized to ovalbumin, were anesthetized and curarized before being challenged, during controlled ventilation, with antigen administered as an aerosol. Antigen challenge was performed before and after pretreatment with nebulized FPL55712 and BW755C, respectively used as an antagonist of leukotrienes and as a cyclo-oxygenase/lipoxygenase inhibitor. The experiments were carried out during continuous recording of tracheal pressure (Ptr), airflow (V) and tidal volume (VT) signals variations evidencing respiratory asynchronism (AS) and allowing measurements of the changes in airway resistance (AR) and dynamic compliance (Cdyn) during all the challenge. Administration of nebulized ovalbumin was stopped at the onset of AS appearance chosen as the threshold of the antigen-induced bronchoconstriction. The results showed that separate or combined pretreatment with FPL55712 and BW755C did not significantly modify the threshold of the ovalbumin-induced bronchoconstriction in guinea-pigs. Nevertheless pretreatment with nebulized FPL55712 reduced significantly the intensity and the duration of the response of these animals to inhaled leukotriene D4 (LTD4). Moreover the response of guinea-pigs to inhaled LTD4, characterized by a starting decrease in Cdyn, appeared quite different from the response to the antigen starting by an abrupt rise in RA induced by a sudden bronchoconstriction. From these results, we concluded that leukotrienes seem not to be the main mediator of the bronchial anaphylaxis in guinea-pigs.

Effects of PEEP on systemic venous capacitance.

The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.