Prehospital triage of acute aortic syndrome using a machine learning algorithm.

BACKGROUND: Acute aortic syndrome (AAS) comprises a complex and potentially fatal group of conditions requiring emergency specialist management. The aim of this study was to build a prediction algorithm to assist prehospital triage of AAS. METHODS: Details of consecutive patients enrolled in a regional specialist aortic network were collected prospectively. Two prediction algorithms for AAS based on logistic regression and an ensemble machine learning method called SuperLearner (SL) were developed. Undertriage was defined as the proportion of patients with AAS not transported to the specialist aortic centre, and overtriage as the proportion of patients with alternative diagnoses but transported to the specialist aortic centre. RESULTS: Data for 976 hospital admissions between February 2010 and June 2017 were included; 609 (62·4 per cent) had AAS. Overtriage and undertriage rates were 52·3 and 16·1 per cent respectively. The population was divided into a training cohort (743 patients) and a validation cohort (233). The area under the receiver operating characteristic (ROC) curve values for the logistic regression score and the SL were 0·68 (95 per cent c.i. 0·64 to 0·72) and 0·87 (0·84 to 0·89) respectively (P < 0·001) in the training cohort, and 0·67 (0·60 to 0·74) and 0·73 (0·66 to 0·79) in the validation cohort (P = 0·038). The logistic regression score was associated with undertriage and overtriage rates of 33·7 (bootstrapped 95 per cent c.i. 29·3 to 38·3) and 7·2 (4·8 to 9·8) per cent respectively, whereas the SL yielded undertriage and overtriage rates of 1·0 (0·3 to 2·0) and 30·2 (25·8 to 34·8) per cent respectively. CONCLUSION: A machine learning prediction model performed well in discriminating AAS and could be clinically useful in prehospital triage of patients with suspected AAS.

ANTECEDENTES: Los síndromes aórticos agudos (aortic acute syndromes, AAS) constituyen un grupo complejo y potencialmente letal de entidades que requieren un tratamiento especializado en emergencias. El objetivo de este estudio fue construir un algoritmo de predicción para ayudar a la selección prehospitalaria de los AAS. MÉTODOS: Se recogieron prospectivamente una serie de pacientes consecutivos inscritos en una red regional especializada en patología aórtica. Se desarrollaron dos algoritmos de predicción para AAS basados en una regresión logística y en un método de aprendizaje automático denominado Super Learner (SL). Undertriage (infra-selección) se definió como la proporción de pacientes con AAS no transportados al centro especializado en patología aórtica y el overtriage (sobre-selección) como la proporción de pacientes con diagnósticos alternativos al AAS pero transportados al centro especializado en patología aórtica. RESULTADOS: Se incluyeron los datos de 976 ingresos hospitalarios entre febrero de 2010 y junio de 2017, con 609 (62,4%) AAS. Las tasas de overtriage y undertriage fueron del 52,3% y del 16,1%, respectivamente. La población se dividió en una cohorte de entrenamiento (n = 743) y en una cohorte de validación (n = 233). El área bajo la curva ROC para la puntuación de regresión logística y el SL fueron de 0,68 (0,64, 0,72) y de 0,87 (0,84, 0,89), respectivamente (P < 0,001) en la cohorte de entrenamiento, y de 0,67 (0,60, 0,74) y de 0,73 (0,66, 0,79) en la cohorte de validación (P = 0,038). La puntuación de regresión logística se asoció con tasas de undertriage y overtriage de 33,7% (i.c. del 95% bootstrapped 29,3%, 38,3%) y de 7,2% (4,8%, 9,8%), respectivamente, mientras que el SL presentó tasas de undertriage y overtriage de 1,0% (0,3%, 2,0%) y de 30,2% (25,8%, 34,8%), respectivamente. CONCLUSIÓN: El modelo de predicción de aprendizaje automático funcionó bien para discriminar AAS y podría ser clínicamente útil en la selección prehospitalaria de pacientes con sospecha de síndrome aórtico agudo.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Comparison of two versions of the Vigileo-FloTrac system (1.03 and 1.07) for stroke volume estimation: a multicentre, blinded comparison with oesophageal Doppler measurements.

BACKGROUND: Our aim was to evaluate the validity of stroke volume measurements obtained using the Vigileo-FloTrac system in comparison with those obtained using oesophageal Doppler considered as a reference. METHODS: Prospective, multicentre study (four university hospitals), in which investigators were blinded to stroke volume values acquired simultaneously with the other technique. Two different versions of the Vigileo software (1.03 and 1.07) were studied and compared over two consecutive periods of time. Forty critically ill patients (three ICUs) and 20 high-risk surgical patients (one operating theatre) were studied over a 6-month period. RESULTS: Two hundred and forty paired stroke volume values obtained using the second version of the Vigileo (1.07) yielded better correlation and agreement (R=0.48, P<0.001; bias=4 ml, limits of agreement: +/- 41 ml) than the 207 paired values obtained using version 1.03 (R=0.12, P=0.1; bias=1 ml, limits of agreement: +/- 75 ml). However, even with the second version, the percentage error in stroke volume measurement was 58%, a value still above the range considered clinically acceptable (30%). CONCLUSIONS: The precision of stroke volume estimation using Vigileo-FloTrac has improved with the second version of the software (1.07), but remains insufficient to allow the replacement of the reference technique in the population studied.

Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

PURPOSE: The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. MATERIAL AND METHODS: This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18FDG-PET-CT tumor uptake at 6months. RESULTS: Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18FDG-PET CT follow-up. CONCLUSION: Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance.

Effects of left ventricular pressure on sonicated albumin microbubbles: evaluation using an isolated rabbit heart model.

OBJECTIVES: We used an isolated, crystalloid-perfused rabbit heart model to test the hypothesis that the phasic changes in left ventricular contrast are due to bubble compression and decompression during systole and diastole, respectively. BACKGROUND: Contrast enhancement of the left ventricular cavity has been shown to decrease during ventricular systole. This phenomenon has been attributed to pressure-induced microbubble destruction. Such destruction, if confirmed, would severely confound the quantitative interpretation of contrast echocardiographic data. METHODS: A fixed volume of contrast solution (5% human albumin and Albunex, approximately 400:1 ratio) was introduced into a latex balloon placed within the left ventricular cavity of an isolated paced rabbit heart preparation (n = 12). Instantaneous left ventricular pressure was measured using a high fidelity microtip catheter and digitized on-line. The beating heart was placed in a water tank, and ultrasound images were obtained using a 7.5-MHz transducer and were recorded and digitized off-line at 12 frames/s. Simultaneously, the pacing signal was used for gated on-line acquisition of end-diastolic frames. A simple theoretic model based on surface tension physical principles was used to predict changes in bubble size and, consequently, the reflection intensity in response to the measured changes in left ventricular pressure. RESULTS: We found that under peak left ventricular systolic pressures ranging from 89 to 155 mm Hg, 1) end-diastolic videointensity decreased by 8 +/- 6% (mean +/- SD) over 25 consecutive heart beats; and 2) intracyclic variations in measured videointensity were in close agreement with the theoretic calculations: 80.1 +/- 2.9% versus 80.2 +/- 4.6% of diastolic videointensity at systole. CONCLUSIONS: The major cause of systolic decrease in contrast enhancement is periodic bubble compression (as opposed to bubble destruction) induced by high systolic pressures. The minor progressive decrease in end-diastolic videointensity reflects the degree of instability of Albunex microbubbles under left ventricular pressures. However, the clinical impact of these destructive effects is likely to be only minor because of the rapid transit of microbubbles through the left heart chambers and myocardial microcirculation.

Involvement of Wnt-1 in the formation of the mes/metencephalic boundary.

Wnt-1, a putative signaling molecule, is required before the 7 somite stage (E8.5) for the development of midbrain structures in the mouse. We show here that Wnt-1 is also needed for the formation of a boundary between the mesencephalic and metencephalic domains of the neural tube. In embryos homozygous for the Wnt-1sw allele, mesencephalic and metencephalic markers fail to segregate and the establishment of a straight limit of Otx-2 and Wnt-1 expression at the mid-hindbrain junction is impaired. In addition, as observed previously in heterotopic mes/metencephalic transplantation experiments in avian embryos, Wnt-1 expression is induced at the border of ectopic mes- and metencephalic islands observed in Wnt-1sw/sw mutants, suggesting that, in situ, interactions between mes- and metencephalic cells reinforce Wnt-1 expression at the boundary.

Psychiatric consequences of intraoperative awareness: short review and case series.

Intraoperative awareness is an unwanted outcome that consists of an explicit recall of events during a surgical procedure performed under general anesthesia. Despite its relatively infrequent occurrence, intraoperative awareness is of significant concern due to frequent adverse psychiatric sequelae. We present three patients who developed posttraumatic sequelae following an episode of awareness under anesthesia and discuss the importance of early detection and specific care.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

Development of the olivocerebellar projection in the rat: II. Matching of the developmental compartmentations of the cerebellum and inferior olive through the projection map.

A transient biochemical parcellation has been observed by immunocytochemical methods, during the perinatal development of both the inferior olive and the cerebellum. In the present study, we sought a relationship between this developmental compartmentation and the organization of the olivocerebellar projection. In the inferior olive, a transient parvalbumin immunoreactivity restricted to the dorsal cap of the medial accessory olive is observed around birth. The climbing fiber projection of the dorsal cap was identified in the cerebellum of newborn rats based on its parvalbumin immunoreactivity. The pattern of this projection, restricted to lobules IX and X of the vermis, and to the flocculus, is indistinguishable from that of the adult medial accessory olive, which was previously described from axonal tracing experiments. The parvalbumin immunoreactive climbing fibers were followed between birth and postnatal day 7. In the caudal vermis, Purkinje cell subpopulations can be identified between embryonic day 20 and postnatal day three, on the basis of their differential immunostaining with an antibody directed against a specific peptide, PEP 19. In lobule X, the parvalbumin immunoreactive climbing fibers form two sagittal bands on each side of the midline, one medial and one lateral. The medial parvalbumin immunoreactive climbing fiber band is coextensive with a PEP 19 negative Purkinje cell cluster, indicating a clear relationship between the biochemical parcellations of the cerebellum and inferior olive.

Development of the olivocerebellar projection in the rat: I. Transient biochemical compartmentation of the inferior olive.

In the present study the early phases of the development of the inferior olive were examined by using immunocytochemical techniques. We observed that, from embryonic day 16 onward, antibodies against the calcium binding proteins parvalbumin and calbindin and the calcitonin gene related peptide stain partially overlapping territories of the inferior olive. This staining delimits a biochemical zonation of the inferior olive which is combinatory and transient. We have previously observed a biochemical parcellation of the cerebellar Purkinje cells which, like that of the inferior olive, is first observed at E16, involves the combined expression of marker proteins and is also transient. In order to know whether the biochemical compartmentations of the cerebellum and inferior olive arise independently, the time course of the development of the olivocerebellar projection was studied by anterograde and retrograde in vitro axonal tracing by using the fluorescent carbocyanine dye DiI. The olivocerebellar axons were found to reach the limit of the cerebellar plate at E16 and to enter it at E17. Even at this age the great majority of the climbing fibers are tightly fasciculated, which minimizes their interactions with the PC clusters. These observations indicate that the topographical heterogeneity of Purkinje cells and inferior olive neurons arise independently. The transient biochemical individualization of subgroups of neurons during development could contribute to recognition mechanisms.

High tumor necrosis factor serum level is associated with increased survival in patients with abdominal septic shock: a prospective study in 59 patients.

BACKGROUND: In several studies including patients with septic shock of various origins, high serum cytokine levels have been reported to correlate with poor outcome. The aim of this prospective study was to assess the prognostic value of cytokine serum levels in a group of patients with perioperative septic shock of digestive origin. METHODS: From January 1992 to December 1994, 59 patients were evaluated (mean age, 68 +/- 15 years). From the first day of septic shock to day 7, blood was drawn every day to measure the conventional biologic parameters (white blood cell count, platelet count, hematocrit, blood urea nitrogen level, serum electrolytes level, pH, blood gases, serum lactate level, coagulation parameters, liver function tests) and tumor necrosis factor (TNF), interleukin-1, and interleukin-6. RESULTS: No difference was observed between the 26 survivors and the 33 nonsurvivors with regard to age, gender, and cause of sepsis. On admission, mean platelet count was significantly higher in the survivors than in the nonsurvivors (260 +/- 142 versus 177 +/- 122 10(9)/L; p = 0.01). Mean blood urea nitrogen level was significantly lower in the survivors than in the nonsurvivors (9.6 +/- 9 versus 12 +/- 7 mmol/L; p = 0.04). No difference was observed between survivors and nonsurvivors for the other conventional biologic parameters and for serum interleukin-1 and interleukin-6 levels. Mean serum TNF level tended to be higher in survivors than in nonsurvivors (565 +/- 1325 versus 94 +/- 69 pg/ml; not significant). In the group survivor 9 (35%) of 26 patients had a serum TNF level greater than 200 pg/ml versus 2 (6%) of 33 patients in the nonsurvivor group (p < 0.02). Survival was noted in 6 (100%) of 6 patients who had both a serum TNF level greater than 200 pg/ml and a platelet count greater than 100.10(9)/L versus 1 (11%) of 9 in patients with neither of these criteria (p < 0.01). CONCLUSIONS: In our patients with abdominal septic shock, high serum TNF levels were associated with increased survival. The high serum level of TNF may reflect the efficacy of peritoneal inflammatory response against abdominal sepsis. Although this possibility must be further explored, a score combining the serum TNF level and platelet count could be helpful for the prognostic assessment of patients with abdominal septic shock.

Smooth muscle relaxation and local hydraulic impedance properties of the aorta.

Smooth muscle relaxation is expected to yield beneficial effects on hydraulic impedance properties of large vessels. We investigated the effects of intravenous diltiazem infusion on aortic wall stiffness and local hydraulic impedance properties. In seven anesthetized, closed-chest dogs, instantaneous cross-sectional area and pressure of the descending thoracic aorta were measured using transesophageal echocardiography combined with acoustic quantification and a micromanometer, respectively. Data were acquired during a vena caval balloon inflation, both at the control condition and with diltiazem infusion. At the operating point, diltiazem reduced blood pressure in all dogs but did not alter aortic dimensions or wall stiffness. Over the observed pressure range, aortic area-pressure relationships were linear. Whereas diltiazem affected the slope of this relationship variably (no change in 3 dogs, increase in 1 dog, decrease in 3 dogs), the zero-pressure area intercept was significantly increased in every case such that higher area was observed at any given pressure. When comparisons were made at a common level of wall stress, wall stiffness was either increased or unchanged during diltiazem infusion. In contrast, diltiazem decreased wall stiffness in every case when comparisons were made at a common level of aortic midwall radius. Aortic characteristic impedance and pulse wave velocity, components of left ventricular hydraulic load that are determined by aortic elastic and geometric properties, were affected variably. A comparison of wall stiffness at matched wall stress appears inappropriate for assessing changes in smooth muscle tone. Because of the competing effects of changes in vessel diameter and wall stiffness, smooth muscle relaxation is not necessarily accompanied by the expected beneficial changes in local aortic hydraulic impedance. These results can be reconciled by recognizing that components other than vascular smooth muscle (e.g., elastin, collagen) contribute to aortic wall stiffness.

Changes in lower limb volume in humans during parabolic flight.

Variations in gravity [head-to-foot acceleration (Gz)] induce hemodynamic alterations as a consequence of changes in hydrostatic pressure gradients. To estimate the contribution of the lower limbs to blood pooling or shifting during the different gravity phases of a parabolic flight, we measured instantaneous thigh and calf girths by using strain-gauge plethysmography in five healthy volunteers. From these circumferential measurements, segmental leg volumes were calculated at 1, 1.7, and 0 Gz. During hypergravity, leg segment volumes increased by 0.9% for the thigh (P < 0.001) and 0.5% for the calf (P < 0.001) relative to 1-Gz conditions. After sudden exposure to microgravity following hypergravity, leg segment volumes were reduced by 3.5% for the thigh (P < 0.001) and 2.5% for the calf (P < 0.001) relative to 1.7-Gz conditions. Changes were more pronounced at the upper part of the leg. Extrapolation to the whole lower limb yielded an estimated 60-ml increase in leg volume at the end of the hypergravity phase and a subsequent 225-ml decrease during microgravity. Although quantitatively less than previous estimations, these blood shifts may participate in the hemodynamic alterations observed during hypergravity and weightlessness.

Proximal trajectory of the brachium conjunctivum in rat fetuses and its early association with the parabrachial nucleus. A study combining in vitro HRP anterograde axonal tracing and immunocytochemistry.

The proximal course of the developing brachium conjunctivum (BC) in the rat described from embryonic day 16 (E16) to one day postnatal (P1). Axons of the cerebellar deep nuclear neurons entering this bundle were identified by anterograde axonal tracing after in vitro horseradish peroxidase (HRP) injections in the cerebellar plate. At all ages, the main ascending limb of the BC can be followed from its emergence, dorsal to the cerebellar plate where it assumes an almost vertical course, up to its decussation. Close to the ventricle at E16, the decussating fibers are progressively displaced ventrally probably because of the fusion, on the midline, of bilaterally produced raphe neurons. In E16 and E17 embryos, labeled BC fibers extend beyond the decussation in the caudal part of the red nucleus. Decussating BC axons, in some E16 early embryos, end with large and complicated growth cones, as described previously in 'decision regions' for chick embryo motoneurons. Growth cones were never observed in this region in older embryos. In addition to the main ascending limb of the BC, we also traced its ipsilateral descending limb and the cerebello-olivary projections. In parallel, the development of a nucleus immunoreactive for the vitamin D-dependent calcium-binding protein (CaBP) is reported. By E16, its neurons migrate rostrally and settle in the region where the BC is demonstrated by tracing experiments. At E17 and thereafter this isthmic nucleus is composed of a shell of CaBP-immunoreactive neurons ensheathing an immunonegative cylinder. Between E17 and birth, in spite of the profound modifications of the isthmic region, this CaBP-immunoreactive nucleus remains in close proximity to the BC. This nucleus is identified as the marginal nucleus of the BC or parabrachial nucleus, by double-labeling experiments combining the visualization of the retrogradely labeled axons and neurons of the deep cerebellar nuclei inside the CaBP immunofluorescently labeled parabrachial nucleus. Subsequently the deep cerebellar neurons translocate caudoventrally moving away from the parabrachial nucleus inside which their axons become visible. This pattern of migration could indicate that a few neurons of the deep nuclei remain ectopic, wedged between the restiform body and the BC while receiving an appropriate Purkinje cell (PC) projection.

Aortic elastic properties with transesophageal echocardiography with automated border detection: validation according to regional differences between proximal and distal descending thoracic aorta.

We have previously described the use of transesophageal echocardiography with automated border detection to quantify regional aortic elastic properties. The purpose of this study was to validate this technique further by measuring regional variations of aortic elastic properties and comparing them with previously published data acquired by invasive methods. In nine anesthetized, closed-chest dogs, aortic pressure and lumenal area (transesophageal echocardiography with automated border detection) signals were recorded simultaneously at two aortic sites: just distal to the branching site of the left subclavian artery (proximal) and at the level of the diaphragm (distal). Instantaneous wall thickness was estimated by combining M-mode measurement of aortic end-diastolic thickness with instantaneous lumenal area. Data were acquired over a wide range of loading conditions, generated by inferior vena caval balloon occlusion. Aortic compliance per unit length, midwall radius, midwall stress, and incremental elastic modulus were computed. Aortic midwall radius and incremental elastic modulus values for proximal and distal aortic sites were compared at a common level of midwall stress. Compliance per unit length was higher in the proximal compared with the distal descending thoracic aorta (0.013 +/- 0.003 versus 0.008 +/- 0.003 cm2/mm Hg; mean +/- SD; p = 0.0011). Midwall radius was larger at the proximal location (0.76 +/- 0.07 cm versus 0.64 +/- 0.07 cm; p = 0.0001), whereas incremental elastic modulus was greater distally (0.799 +/- 0.052 dynes x 10(6)/cm2 versus 0.912 +/- 0.130 dynes x 10(6)/cm2; p = 0.02). Lower compliance values at the distal site of the descending thoracic aorta resulted from greater wall stiffness and a smaller radius. Transesophageal echocardiography with automated border detection provides reliable measurements of instantaneous aortic areas necessary for quantifying regional elastic properties.

Echocardiographic contrast agents and left ventricular contractility: evaluation using an isolated rabbit heart model.

The effects of Albunex (Molecular Biosystems, Inc., San Diego, Calif.) and a second generation contrast agent, FS069, on left ventricular (LV) contractility were evaluated using an isolated rabbit heart model under constant loading conditions and heart rate. Contrast injections (2 ml total volume) were performed in two separate protocols (N1 = 6, N2 = 6). In protocol 1, various doses of Albunex (0.1 to 2.0 ml in saline solution) were used, and paired control injections of a matched dose of 5% solution of human albumin in saline solution were administered. In protocol 2, LV contractility was assessed during injections of the following solutions: (1) 1:250 suspension of FS069 in saline solution, which caused optimal myocardial contrast enhancement; (2) a 1:25 suspension of FS069; (3) a 1:25 suspension of FS069 prefiltered using an 8 microns pore filter; and (4) 2 ml saline solution as a control. Instantaneous LV pressure was analyzed for variations in peak systolic pressure (peak P) and maximum pressure derivative (peak P'), both indices of LV contractility under conditions of fixed heart rate and chamber volume. Albumin alone caused a transient, dose-dependent depression of LV contractility, reflected by decreases in both peak P and peak P' values. These decreases presumably were caused by the decreasing availability of ionized calcium as a result of calcium binding. No further decrease in contractility was noted when Albunex microspheres were present in the solution. Saline injections caused a transient minor increase in LV contractility, reflected by increases of 4.5% +/- 1.1% and 10.6% +/- 3.8% in peak P and peak P' values, respectively. These levels returned to baseline levels within 2 minutes. A similar response was observed when a 1:250 suspension of FS069 was used. The 1:25 suspension of FS069 caused a bimodal response, with initial rises in peak P and peak P' levels (5.2% +/- 3.6% and 12.8% +/- 6.5%, respectively), followed by minor reductions in contractility (2.0% +/- 2.4% and 1.7% +/- 2.1%, respectively). The latter decrease in contractility caused by the 1:25 suspension of FS069 was eliminated by filtering. The isolated rabbit heart model is a highly sensitive tool that allows accurate and direct assessment of possible adverse effects of intravascular contrast agents on LV contractility. Using this model, we showed that neither Albunex microspheres nor FS069 microspheres impaired myocardial contractility.

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter]. / Effets modulateurs de collyres anti-allergiques sur l'activation du complément induite in vitro par des polluants particulaires.

BACKGROUND: Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation. PURPOSE: To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants. METHODS: Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested. RESULTS: Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface. CONCLUSION: Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.