Time course of haemodynamic, respiratory and inflammatory disturbances induced by experimental acute pulmonary polystyrene microembolism

Background and objective The time course of cardiopulmonary alterations after pulmonary embolism has not been clearly demonstrated and nor has the role of systemic inflammation on the pathogenesis of the disease. This study aimed to evaluate over 12 h the effects of pulmonary embolism caused by polystyrene microspheres on the haemodynamics, lung mechanics and gas exchange and on interleukin-6 production. Methods Ten large white pigs (weight 35-42 kg) had arterial and pulmonary catheters inserted and pulmonary embolism was induced in five pigs by injection of polystyrene microspheres (diameter similar to 300 mu mol l(-1)) until a value of pulmonary mean arterial pressure of twice the baseline was obtained. Five other animals received only saline. Haemodynamic and respiratory data and pressure-volume curves of the respiratory system were collected. A bronchoscopy was performed before and 12 h after embolism, when the animals were euthanized. Results The embolism group developed hypoxaemia that was not corrected with high oxygen fractions, as well as higher values of dead space, airway resistance and lower respiratory compliance levels. Acute haemodynamic alterations included pulmonary arterial hypertension with preserved systemic arterial pressure and cardiac index. These derangements persisted until the end of the experiments. The plasma interleukin-6 concentrations were similar in both groups; however, an increase in core temperature and a nonsignificant higher concentration of bronchoalveolar lavage proteins were found in the embolism group. Conclusion Acute pulmonary embolism induced by polystyrene microspheres in pigs produces a 12-h lasting hypoxaemia and a high dead space associated with high airway resistance and low compliance. There were no plasma systemic markers of inflammation, but a higher central temperature and a trend towards higher bronchoalveolar lavage proteins were found. Eur J Anaesthesiol 27:67-76 (C) 2010 European Society of Anaesthesiology.

Fluid Replacement With Hypertonic or Isotonic Solutions Guided by Mixed Venous Oxygen Saturation in Experimental Hypodynamic Sepsis

Background: Splanchnic perfusion is prone to early injury and persists despite normalization of global hemodynamic variables in sepsis. Volume replacement guided by oxygen derived variables has been recommended in the management of septic patients. Our hypothesis was that a hypertonic isoneotic solution Would improve the benefits of crystalloids replacement guided by mixed venous oxygen saturation. Methods: Seventeen anesthetized and mechanically ventilated mongrel dogs received an intravenous infusion of live E. coli in 30 minutes. They were then randomized into three groups: control group (n = 3) bacterial infusion without treatment; normal saline (n = 7), initial fluid replacement with 32 mL/kg of normal saline during 20 minutes; hypertonic solution (n = 7), initial fluid replacement with 4 mL/kg of hypertonic solution during 5 minutes. After 30 and 60 Minutes, additional boluses of normal saline were administered when mixed venous oxygen saturation remained below 70%. Mean arterial pressure, cardiac output; regional blood flows, systemic and regional oxygen-derived variables, and lactate levels were assessed. Animals were observed for 90 minutes and then killed. Hystopathological analysis including apoptosis detection using terminal deoxynucleotidil transferase mediated dUTP-biotin nick end labeling was performed. Results: A hypodynamic septic shock was observed after bacterial infusion. Both the fluid-treated groups presented similar transient benefits in systemic and regional variables. A greater degree of gut epithelial cells apoptosis was observed in normal saline-treated animals. Conclusions: Although normalization of mixed venous oxygen saturation was not associated with restoration of markers of splanchnic or other systemic perfusion variables, the initial fluid savings with hypertonic saline and its latter effect on gut apoptosis may be of interest in sepsis management.

Factors associated with pelvic asymmetry in transverse plane during gait in patients with cerebral palsy

The purpose of this study was to describe the patterns of pelvic rotational asymmetry in the transverse plane and identify the possible factors related to this problem. One thousand and forty-five patients with cerebral palsy (CP) and complete documentation in the gait laboratory were reviewed in a retrospective study. Pelvic asymmetry in the transverse plane was observed in 52.7% of the patients; and to identify the possible causes of pelvic retraction, clinical (Thomas test, popliteal angle, and gastrocnemius tightness) and dynamic parameters (mean rotation of the hip in stance, minimum hip flexion, minimum knee flexion, and peak ankle dorsiflexion) were evaluated. The association between these parameters and pelvic retraction was assessed statistically. The results showed that 75.7% of patients with asymmetric pattern of the pelvis had clinical diagnosis of diplegic spastic CP. Among the patients with asymmetrical CP, the most common pattern was pelvic retraction on the affected side. The relationship between pelvic retraction and internal hip rotation was stronger in patients with asymmetrical diplegic CP than in those with hemiplegic (P<0.001) or symmetrical diplegic CP (P=0.014). All of the patients exhibited a significant association among clinical parameters (Thomas test, popliteal angle, and gastrocnemius tightness) and pelvic retraction. In conclusion, pelvic retraction seems to be a multifactorial problem, and the etiology can change according to topographic classification, which must be taken into account during the decision-making process in patients with CP. J Pediatr Orthop B 18:320-324 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Monoclonal anti-vascular endothelial growth factor antibody reduces fluid volume in an experimental model of inflammatory pleural effusion

Background and objective: Vascular endothelial growth factor (VEGF) is known to increase vascular permeability and promote angiogenesis. It is expressed in most types of pleural effusions. However, the exact role of VEGF in the development of pleural effusions has yet to be determined. The anti-VEGF mAb, bevacizumab, has been used in the treatment of cancer to reduce local angiogenesis and tumour progression. This study describes the acute effects of VEGF blockade on the expression of inflammatory cytokines and pleural fluid accumulation. Methods: One hundred and twelve New Zealand rabbits received intrapleural injections of either talc or silver nitrate. In each group, half the animals received an intravenous injection of bevacizumab, 30 min before the intrapleural agent was administered. Five animals from each subgroup were sacrificed 1, 2, 3, 4 or 7 days after the procedure. Twelve rabbits were used to evaluate vascular permeability using Evans`s blue dye. Pleural fluid volume and cytokines were quantified. Results: Animals pretreated with anti-VEGF antibody showed significant reductions in pleural fluid volumes after talc or silver nitrate injection. IL-8 levels, vascular permeability and macroscopic pleural adhesion scores were also reduced in the groups that received bevacizumab. Conclusions: This study showed that bevacizumab interferes in the acute phase of pleural inflammation induced by silver nitrate or talc, reinforcing the role of VEGF as a key mediator in the production of pleural effusions. The results also suggest that bevacizumab should probably be avoided in patients requiring pleurodesis.

Delay in the Diagnosis of Cerebral Vein and Dural Sinus Thrombosis Influence on Outcome

Background and Purpose-Diagnostic delay of cerebral vein and dural sinus thrombosis may have an impact on outcome. Methods-In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score > 2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field). Results-Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P < 0.001) and of mental status (P = 0.042), seizure (< 0.001), and with parenchymal lesions on admission CT/MR (P < 0.001) were diagnosed earlier, whereas men (P = 0.01) and those with isolated intracranial hypertension syndrome (P = 0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P = 0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P = 0.86) or deaths (P = 0.53). Persistent visual deficits were more frequent in patients diagnosed later (P = 0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score > 2 at the end of follow-up was more frequent in patients diagnosed later (P = 0.02). Conclusions-Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency. (Stroke. 2009; 40: 3133-3138.)

Influence of parecoxib (cox-2 inhibitor) in experimental pleurodesis

Background: The intrapleural instillation of a sclerosing agent produces an inflammatory process frequently followed by pain. The treatment can include the use of analgesics or anti-inflammatory drugs. Previously, it was demonstrated (experimental studies) that corticoids and nonsteroidal anti-inflammatory drugs (diclofenac) reduce the inflammation and fibrosis produced by talc but not by transforming growth factor-P or silver nitrate. The objective of this study was to determine whether parecoxib (COX-2 inhibitor) affects pleurodesis induced by talc or silver nitrate. Methods: 140 rabbits received intrapleural. injection (2 mL) of 400 mg/kg of talc or 0.5% silver nitrate. A subgroup of 70 animals received additional daily intramuscular parecoxib (1 mg/kg). They were sacrificed at 4, 24, 48, 72 h or 7, 14, or 28 days after the procedure. The pleural fluid was quantified; biochemical examinations (glucose, lactic dehydrogenase, and proteins) and immunologic dosages (interleukin-8, vascular endothelial growth factor, and transforming growth factor-beta(1)) were analyzed in pleural fluid and blood. Finally, macro- and microscopic pleura and lung studies were performed. Results: Evaluation after 28 days demonstrated that parecoxib reduced pleural and pulmonary inflammation but not pleural adhesions. The changes were observed precociously (72 h) and were more evident after silver nitrate injection. Conclusion: Systemic parecoxib injection does not interfere with talc or silver nitrate pleurodesis. These results suggest that use of COX-2 inhibitors can be considered and depending of the results of other studies, recommended in human pleurodesis. (c) 2008 Elsevier Ltd. All rights reserved.

GIANT FUSIFORM ANEURYSM ARISING FROM FENESTRATED POSTERIOR CEREBRAL ARTERY AND BASILAR TIP VARIATION: CASE REPORT

OBJECTIVE: A giant fusiform aneurysm in the posterior cerebral artery (PCA) is rare, as is fenestration of the PCA and basilar apex variation. We describe the angiographic and surgical findings of a giant fusiform aneurysm in the P1-P2 PCA segment associated with PCA bilateral fenestration and superior cerebellar artery double origin. CLINICAL PRESENTATION: A 26-year-old woman presented with a 2-month history of visual blurring. Digital subtraction angiography showed a giant (2.5 cm) fusiform PCA aneurysm in the right P1-P2 segment. The 3-dimensional view showed a caudal fusion pattern from the upper portion of the basilar artery associated with a bilateral long fenestration of the P1 and P2 segments and superior cerebellar artery double origin. INTERVENTION: Surgical trapping of the right P1 -P2 segment, including the posterior communicating artery, was performed by a pretemporal approach. Angiograms performed 3 and 13 months after surgery showed complete aneurysm exclusion, and the PCA was permeated and filled the PCA territory. Clinical follow-up at 14 months showed the patient with no deficits and a return to normal life. CONCLUSION: To our knowledge, this is the first report of a giant fusiform aneurysm of the PCA associated with P1-P2 segment fenestration and other variations of the basilar apex (bilateral superior cerebellar artery duplication and caudal fusion). Comprehension of the embryology and anatomy of the PCA and its related vessels and branches is fundamental to the decision-making process for a PCA aneurysm, especially when parent vessel occlusion is planned.

Assessment of a New Experimental Model of Isolated Right Ventricular Failure

We assessed a new experimental model of isolated right ventricular (RV) failure, achieved by means of intramyocardial injection of ethanol. RV dysfunction was induced in 13 mongrel dogs via multiple injections of 96% ethanol (total dose 1 mL/kg), all over the inlet and trabecular RV free walls. Hemodynamic and metabolic parameters were evaluated at baseline, after ethanol injection, and on the 14th postoperative day (POD). Echocardiographic parameters were evaluated at baseline, on the sixth POD, and on the 13th POD. The animals were then euthanized for histopathological analysis of the hearts. There was a 15.4% mortality rate. We noticed a decrease in pulmonary blood flow right after RV failure (P = 0.0018), as well as during reoperation on the 14th POD (P = 0.002). The induced RV dysfunction caused an increase in venous lactate levels immediately after ethanol injection and on the 14th POD (P < 0.0003). The echocardiogram revealed a decrease in the RV ejection fraction on the sixth and 13th PODs (P = 0.0001). There was an increased RV end-diastolic volume on the sixth (P = 0.0001) and 13th PODs (P = 0.0084). The right ventricle showed a 74% +/- 0.06% transmural infarction area, with necrotic lesions aged 14 days. Intramyocardial ethanol injection has allowed the creation of a reproducible and inexpensive model of RV failure. The hemodynamic, metabolic, and echocardiographic parameters assessed at different protocol times are compatible with severe RV failure. This model may be useful in understanding the pathophysiology of isolated right-sided heart failure, as well as in the assessment of ventricular assist devices.

Risk Score to Predict the Outcome of Patients with Cerebral Vein and Dural Sinus Thrombosis

Background: Around 15% of patients die or become dependent after cerebral vein and dural sinus thrombosis (CVT). Method: We used the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) sample (624 patients, with a median follow-up time of 478 days) to develop a Cox proportional hazards regression model to predict outcome, dichotomised by a modified Rankin Scale score > 2. From the model hazard ratios, a risk score was derived and a cut-off point selected. The model and the score were tested in 2 validation samples: (1) the prospective Cerebral Venous Thrombosis Portuguese Collaborative Study Group (VENO-PORT) sample with 91 patients; (2) a sample of 169 consecutive CVT patients admitted to 5 ISCVT centres after the end of the ISCVT recruitment period. Sensitivity, specificity, c statistics and overall efficiency to predict outcome at 6 months were calculated. Results: The model (hazard ratios: malignancy 4.53; coma 4.19; thrombosis of the deep venous system 3.03; mental status disturbance 2.18; male gender 1.60; intracranial haemorrhage 1.42) had overall efficiencies of 85.1, 84.4 and 90.0%, in the derivation sample and validation samples 1 and 2, respectively. Using the risk score (range from 0 to 9) with a cut-off of 6 3 points, overall efficiency was 85.4, 84.4 and 90.1% in the derivation sample and validation samples 1 and 2, respectively. Sensitivity and specificity in the combined samples were 96.1 and 13.6%, respectively. Conclusions: The CVT risk score has a good estimated overall rate of correct classifications in both validation samples, but its specificity is low. It can be used to avoid unnecessary or dangerous interventions in low-risk patients, and may help to identify high-risk CVT patients. Copyright (C) 2009 S. Karger AG, Basel

Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

Background and objective The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Methods Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 ml kg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1 : 2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 ml kg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2: 1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). Results During baseline, a positive end-expiratory pressure of 15cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P<0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P<0.001). High tidal volume increased pulse pressure variation from 15.8 8.5% to 31.6 +/- 10.4% (P<0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1 % post, P<0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without without affecting pulse pressure variation or right ventricle end-diastolic volume. Conclusion We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters. Eur J Anaesthesiol 26:66-72 (c) 2009 European Society of Anaesthesiology.

Initial hepatosplanchnic blood flow distribution and oxygen metabolism in experimental model of hypotensive brain death

Background: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. Material/Methods: Ten dogs (21.3 +/- 0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without ally additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. Results: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0 +/- 0.2 VS. 2.8 +/- 2.8 L/min) and PVBF (687 +/- 114 vs. 623 +/- 130 ml/min) was observed, whereas HABF (277 33 vs. 134 28 ml/min, p<0.005) remained lower than baseline values. Conclusions: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.

Are the recommendations from three-dimensional gait analysis associated with better postoperative outcomes in patients with cerebral palsy?

This study was performed to check if recommendations based on three-dimensional gait analysis (3DGA) are associated with better postoperative outcomes in patients with cerebral palsy (CP). Thirty-eight patients who underwent orthopedic surgery and assessment at the Gait Analysis Laboratory were evaluated retrospectively. The patients were divided in four groups according to the agreement between the recommendations from gait analysis and the procedures actually carried out. Fifteen patients with diplegic spastic cerebral palsy and indication for orthopedic surgery to improve walking - and whose surgical intervention was postponed - were also included in the study as a control group. Fourteen gait parameters recorded before and after treatment, were included in the statistical analysis. No gait improvement was noted in the control group or inh patients on whom no procedures recommended by the gait exam were performed (agreement of 0%). In the other groups, agreements averaged 46.71%, 72.2%, and 100%, respectively. Improvement of gait parameters after treatment was observed in these groups, with more significant values directly related to increased agreement percentage. Therefore, in this study the patients whose treatment matched the recommendations from three-dimensional gait analysis showed a more significant improvement in walking. (c) 2008 Elsevier B.V. All rights reserved.

Role of promoter polymorphisms in the plasma glutathione peroxidase (GPx-3) gene as a risk factor for cerebral venous thrombosis

Background and Purpose-Plasma glutathione peroxidase (GPx-3) is a major antioxidant enzyme in plasma and the extracellular space that scavenges reactive oxygen species produced during normal metabolism or after oxidative insult. A deficiency of this enzyme increases extracellular oxidant stress, promotes platelet activation, and may promote oxidative posttranslational modification of fibrinogen. We recently identified a haplotype (H-2) in the GPx-3 gene promoter that increases the risk of arterial ischemic stroke among children and young adults. Methods-The aim of this study is to identify possible relationships between promoter haplotypes in the GPx-3 gene and cerebral venous thrombosis (CVT). We studied the GPx-3 gene promoter from 23 patients with CVT and 123 young controls (18 to 45 years) by single-stranded conformational polymorphism and sequencing analysis. Results-Over half of CVT patients (52.1%) were heterozygous (H1H2) or homozygous (H2H2) carriers of the H-2 haplotype compared with 12.2% of controls, yielding a more than 10-fold independent increase in the risk of CVT (OR=10.7; 95% CI, 2.70 to 42.36; P<0.0001). Among women, the interaction of the H2 haplotype with hormonal risk factors increased the OR of CVT to almost 70 (P<0.0001). Conclusions-These findings show that a novel GPx-3 promoter haplotype is a strong, independent risk factor for CVT. As we have previously shown that this haplotype is associated with a reduction in transcriptional activity, which compromises antioxidant activity and antithrombotic benefits of the enzyme, these results suggest that a deficiency of GPx-3 leads to a cerebral venous thrombophilic state.

Composition of Diesel Particles Influences Acute Pulmonary Toxicity: An Experimental Study in MICE

Ambient particles have been consistently associated with adverse health effects, yielding mainly high cardiorespiratory morbidity and mortality. Diesel engines represent a major source of particles in the urban scenario. We aimed to modify the composition of diesel particles, by means of different extraction procedures, to relate changes in chemical profile to corresponding indicators of respiratory toxicity. Male BALB/c mice were nasally instilled with saline, or with diesel particles, treated or not, and assigned to five groups: saline ( SHAM), intact diesel particles (DEP), and diesel particles previously treated with methanol ( METH), hexane ( HEX), or nitric acid (NA). Elemental composition and organic compounds were analyzed. Twenty-four hours after nasal instillation, respiratory parameters were measured and lung tissue was collected for histological analysis. Static elastance was significantly increased in groups DEP and MET in relation to the other groups. HEX and NA were different from DEP but not significantly different from SHAM and METH groups. The difference between dynamic and static elastance was increased in DEP, METH, and NA treatments; HEX was not statistically different from SHAM. DEP and METH groups presented significantly increased upper airways resistance, while DEP, METH, and NA showed higher peripheral airways resistance values. All groups had a higher total resistance than SHAM. DEP, METH, and NA showed significant increased infiltration of polymorphonuclear cells. In conclusion, diesel particles treated with hexane ( HEX) resulted in a respiratory-system profile very similar to that in SHAM group, indicating that hexane treatment attenuates pulmonary inflammation elicited by diesel particles.

Toxoplasma gondii isolates: Multi locus RFLP-PCR genotyping from human patients in Sao Paulo State, Brazil identified distinct genotypes

This study investigated the genetic characteristics of Toxoplasma gondii samples collected from 62 patients with toxoplasmosis in Sao Paulo State, Brazil. DNA samples were isolated from blood, cerebrospinal fluid and amniotic fluids of 25 patients with cerebral toxoplasmosis and AIDS, two patients with acute toxoplasmosis, 12 patients with ocular toxoplasmosis, six newborns with congenital toxoplasmosis and 17 pregnant women with acute infection. Diagnosis of toxoplasmosis was based in clinical, radiological and laboratory features. Genotyping was performed using multilocus PCR-RFLP genetic markers including SAG1, SAG2, 5`- and 3`-SAG2, alt.SAG2, SAG3, BTUB, GRA6, C22-8, c29-2, L358, PK1 and Apico. Among the 62 clinical samples, 20 (32%) were successfully genotyped at eight or more genetic loci and were grouped to three distinct genotypes. Eighteen samples belonged to ToxoDB Genotype #65 and the other two samples were identified as ToxoDB Genotypes #6 and #71, respectively (http://toxodb.org/toxo/). Patients presenting Genotypes #6 and #71 had severe and atypical cerebral toxoplasmosis, characterized by diffuse encephalitis without extensive brain lesions. These results indicate that T. gondii Genotype #65 may have a high frequency in causing human toxoplasmosis in Sao Paulo State, Brazil. This unusual finding highlights the need to investigate the possible association of parasite genotypes with human toxoplasmosis. (C) 2011 Elsevier Inc. All rights reserved.