In situ visualization of aortic dissection propagation in notched rabbit aorta using synchrotron X-ray tomography.

Aortic dissection is a complex, intramural, and dynamic condition involving multiple mechanisms, hence, difficult to observe. In the present study, a controlled in vitro aortic dissection was performed using tension-inflation tests on notched rabbit aortic segments. The mechanical test was combined with conventional (cCT) and synchrotron (sCT) computed tomography for in situ imaging of the macro- and micro-structural morphological changes of the aortic wall during dissection. We demonstrate that the morphology of the notch and the aorta can be quantified in situ at different steps of the aortic dissection, and that the notch geometry correlates with the critical pressure. The phenomena prior to propagation of the notch are also described, for instance the presence of a bulge at the tip of the notch is identified, deforming the remaining wall. Finally, our method allows us to visualize for the first time the propagation of an aortic dissection in real-time with a resolution that has never previously been reached. STATEMENT OF SIGNIFICANCE: With the present study, we investigated the factors leading to the propagation of aortic dissection by reproducing this mechanical process in notched rabbit aortas. Synchrotron CT provided the first visualisation in real-time of an aortic dissection propagation with a resolution that has never previously been reached. The morphology of the intimal tear and aorta was quantified at different steps of the aortic dissection, demonstrating that the early notch geometry correlates with the critical pressure. This quantification is crucial for the development of better criteria identifying patients at risk. Phenomena prior to tear propagation were also described, such as the presence of a bulge at the tip of the notch, deforming the remaining wall.

Multi-view digital image correlation systems for in vitro testing of arteries from mice to humans.

Background: Digital image correlation (DIC) methods are increasingly used for non-contact optical assessment of geometry and deformation in soft tissue biomechanics, thus providing the full-field strain estimates needed for robust inverse material characterization. Despite the well-known flexibility and ease of use of DIC, issues related to spatial resolution and depth-of-field remain challenging in studies of quasi-cylindrical biological samples such as arteries. Objective: After demonstrating that standard surrounding multi-view DIC systems are inappropriate for such usage, we submit that both the optical setup and the data analysis need to be specifically designed with respect to the size of the arterial sample of interest. Accordingly, we propose novel and optimized DIC systems for two distinct ranges of arterial diameters: less than 2.5 mm (murine arteries) and greater than 10 mm (human arteries). Methods: We designed, set up, and validated a four-camera panoramic-DIC system for testing murine arteries and a multi-biprism DIC system for testing human arteries. Both systems enable dynamic 360-deg measurements with refraction correction over the entire surface of submerged samples in their native geometries. Results: Illustrative results for 3D shape and full-surface deformation fields were obtained for a mouse infrarenal aorta and a latex cylinder of size similar to the human infrarenal aorta. Conclusion: Results demonstrated the feasibility and accuracy of both proposed methods in providing quantitative information on the regional behavior of arterial samples tested in vitro under physiologically relevant loading.

A combined experimental-numerical lamellar-scale approach of tensile rupture in arterial medial tissue using X-ray tomography.

Aortic dissection represents a serious cardio-vascular disease and life-threatening event. Dissection is a sudden delamination event of the wall, possibly leading to rupture within a few hours. Current knowledge and practical criteria to understand and predict this phenomenon lack reliable models and experimental observations of rupture at the lamellar scale. In an attempt to quantify rupture-related parameters, the present study proposes an analytical model that reproduces a uniaxial test on medial arterial samples observed under X-ray tomography. This model is composed of several layers that represent the media of the aortic wall, each having proper elastic and damage properties. Finite element models were created to validate the analytical model using user-defined parameters. Once the model was validated, an inverse analysis was used to fit the model parameters to experimental curves of uniaxial tests from a published study. Because this analytical model did not consider delamination strength between layers, a finite element model that included this phenomenon was also developed to investigate the influence of the delamination on the stress-strain curve through a sensitivity analysis. It was shown that shear delamination strength between layers, i.e. mode II separation, is essential in the rupture process observed experimentally.

Identification of the in vivo elastic properties of common carotid arteries from MRI: a study on subjects with and without atherosclerosis.

The stiffness of the arterial wall, which is modified by many cardiovascular diseases such as atherosclerosis, is known to be an indicator of vulnerability. This work focuses on the in vivo quantification of the stiffness of the common carotid artery (CCA) by applying the Magnitude Based Finite Element Model Updating (MB-FEMU) method to 13 healthy and diseased volunteers aged from 24 to 76 years old. The MB-FEMU method is based on the minimisation of the deviation between the image of a deformed artery and a registered image of this artery deformed by means of a finite elements analysis. Cross sections of the neck of each subject at different times of the cardiac cycle are recorded using a Phase Contrast cine-MRI. Applanation tonometry is then performed to obtain the blood pressure variations in the CCA throughout a heart beat. First, a time averaged elastic modulus of each CCA between diastole and systole is identified and a stiffening of the artery with age and disease is observed. Second, four elastic moduli are identified during a single heart beat for each artery, highlighting the nonlinear mechanical behaviour of the artery. A stiffening of the artery is observed and quantified at systole in comparison to diastole.

Biomechanical response of varicose veins to elastic compression: a numerical study.

A patient-specific finite-element (FE) model of the human leg is developed to model the stress distribution in and around a vein wall in order to determine the biomechanical response of varicose veins to compression treatment. The aim is to investigate the relationship between the local pressure on the soft tissues induced by wearing the compression garment and the development and evolution of varicose veins and various skin-related diseases such as varicose veins and ulcers. Because experimental data on the mechanical properties of healthy superficial veins and varicose veins are scarce in literature, ultrasound images of in vivo varicose veins are acquired and analysed to extract the material constants using Finite Element Model Updating. The decrease in trans-mural pressure, which conditions the effectiveness of compressive treatments, is computed from the simulation results. This constitutes the original added value of the developed model as decrease in trans-mural pressures cannot be assessed experimentally by any other means. Results show that external compression is effective in decreasing the trans-mural pressure, thereby having a positive effect in the control and treatment of vein-related diseases.

Identification of the material parameters of soft tissues in the compressed leg.

Elastic compression is recommended in prophylaxis and the treatment of venous disorder of the human leg. However, the mechanisms of compression are not completely understood and the response of internal tissues to the external pressure is partially unknown. To address this later issue, a 3D FE model of a human leg is developed. The geometry is derived from 3D CT scans. The FE model is made up of soft tissues and rigid bones. An inverse method is applied to identify the properties of soft tissues which are modelled as hyperelastic, near-incompressible, homogeneous and isotropic materials. The principle is to calibrate the constitutive properties using CT scans carried out with and without the presence of a compression sock. The deformed geometry computed by the calibrated FE model is in agreement with the geometry deduced from the CT scans. The model also provides the internal pressure distribution, which may lead to medical exploitation in the future.

Optimal timing of preoperative intraaortic balloon pump support in high-risk coronary patients.

BACKGROUND: Beneficial effects of preoperative intraaortic balloon pump (IABP) treatment, on outcome and cost, in high-risk patients who have coronary artery bypass grafting have been demonstrated. We conducted a prospective, randomized study to determine the optimal timing for preoperative IABP support in a cohort of high-risk patients. METHODS: Sixty consecutive high-risk patients who had coronary artery bypass grafting (presenting with two or more of the following criteria: left ventricular ejection fraction less than 0.30, unstable angina, reoperation, or left main stenosis greater than 70%) entered the study. Thirty patients did not receive preoperative IABP (controls), 30 patients had preoperative IABP therapy starting 2 hours (T2), 12 hours (T12), or 24 hours (T24), by random assignment, before the operation. Fifty patients had preoperative left ventricular ejection fraction mean, less than 0.30 (less than 0.26+/-0.08), (n = 40) unstable angina, 28% (n = 17) left main stenosis, and 32% (n = 19) were reoperations. RESULTS: Cardiopulmonary bypass was shorter in the IABP groups. There was one death in the IABP group and six in the control group. The complication rate for IABP was 8.3% (n = 5) without group differences. Cardiac index was significantly higher postoperatively (p<0.001) in patients with preoperative IABP treatment compared with controls. There were no significant differences between the three IABP subgroups at any time. The incidence of postoperative low cardiac output was significantly lower in the IABP groups (p<0.001). Intubation time, length of stay in the intensive care unit and the hospital was shorter in the IABP groups (p = 0.211, p<0.001, and p = 0.002, respectively). There were no differences between the IABP subgroups in any of the studied variables. CONCLUSIONS: The beneficial effect of preoperative IABP in high-risk patients who have coronary artery bypass grafting was confirmed. There were no differences in outcome between the subgroups; therefore, at 2 hours preoperatively, IABP therapy can be started.

Genetic variation in a human immunodeficiency virus type 2 live-virus Macaca nemestrina vaccine model.

Four pigtailed macaques were inoculated with an infectious, apathogenic human immunodeficiency virus type 2 (HIV-2) molecular clone (HIV-2KR) and subsequently challenged with a highly pathogenic strain, HIV-2287, together with two naive control animals. After challenge, two animals inoculated with a high dose of the immunizing strain were protected from CD4 decline and immunodeficiency. To examine the role of genetic heterogeneity in protection, fragments of the env gene were amplified from peripheral blood mononuclear cell DNA and plasma RNA of challenged animals by PCR, examined by using a heteroduplex tracking assay (HTA), and sequenced. By HTA, variation was detected principally within the V1 and V2 regions of envelope. Extent of variation in viral DNA clones as assessed by HTA correlated with inoculum size, as did the degree of variation in sequences of clones derived from viral DNA. Conversely, a rapid reduction in the number of plasma viral RNA variants was noted by HTA at 8 weeks postinfection in protected animals; this reduction was not present in naive or unprotected macaques. Sequences derived from plasma viral RNA were found to be more closely related than corresponding viral DNA sequences, and protection correlated with a significant reduction in variation in plasma RNA sequences in animals given the identical inocula of HIV-2287. Nonsynonymous mutations were significantly less prevalent in the protected animals. An additional potential glycosylation site was predicted to be present in the V2 region in all but one clone, and amino acid signatures related to protection were identified in viral DNA and RNA clones within both the V1 and V2 regions. Examination of the role of viral variation in this HIV-2 live-virus vaccine model may provide valuable insights into immunopathogenesis.

Characterization of a molecular clone of HIV type 2 infectious for Macaca nemestrina.

A lambda phage clone containing a full-length HIV-2 provirus, designated HIV-2KR, was obtained from the genomic DNA of Molt4 clone 8 (Molt4/8) lymphoblastic cells infected with the HIV-2PEI2 strain. HIV-2KR is genetically distinct from known HIV-2 isolates, possessing both a unique deletion in the LTR promoter region, and a long rev reading frame. It is replication competent in vitro after transfection into Molt4/8 cells, replicates in a variety of established human T lymphoblastic (Molt-3, Molt4/8, SupT1, H9, C8166) and myelomonocytic (U937) cell lines, and displays prominent cytopathic effects on infection of Molt4/8 cells, reflecting usage of both CCR5 and CXCR4 coreceptors. In addition, HIV-2KR was found to be infectious for human and Macaca nemestrina peripheral blood lymphocytes, and primary human monocyte-macrophage cultures. Intravenous inoculation of cell-free virus into M. nemestrina resulted in infection characterized by transient, low-level viremia and modest temporary decline in CD4 lymphocyte numbers, making HIV-2KR the first HIV-2 molecular clone reported to be infectious for this primate species.

Preoperative intraaortic balloon pump enhances cardiac performance and improves the outcome of redo CABG.

BACKGROUND: Reoperative coronary artery bypass grafting (redo CABG) is associated with an increased operative risk compared with primary CABG. Because the hospital mortality in redo CABG is known to be influenced by poor left ventricular function (left ventricular ejection fraction < or = 0.40), unstable angina, and left main stem stenosis greater than or equal to 70%, a preoperative intraaortic balloon pump (IABP) support could be beneficial to improve the outcome in high-risk redo CABG. METHODS: Between June 1994 and October 1996, 48 high-risk patients underwent redo CABG and were randomized into the following groups: group 1 (24 patients) who received preoperative IABP treatment on average 2 hours before cardiopulmonary bypass, and group 2 (24 patients) who received no preoperative IABP and served as controls. Mean age was 65 years and 90% (43 patients) were men. Forty-one patients had preoperative left ventricular ejection fraction less than or equal to 0.40 (85%), 38% (18 patients) had left main stem stenosis greater than or equal to 70%, and 54% (26 patients) had unstable angina preoperatively. Preoperative patient characteristics did not differ between the groups. RESULTS: The time on cardiopulmonary bypass was shorter in group 1, 86 versus 110 minutes (p = 0.006). There were no hospital deaths in group 1, but four deaths occurred in the control group (p = 0.049). Cardiac index rose significantly preoperatively after introduction of the IABP in group 1. Cardiac index was significantly higher postoperatively in group 1 compared with group 2 and remained significantly higher during the first 24 hours after cardiopulmonary bypass. Significantly fewer patients in the IABP group had postoperative low cardiac output (4 versus 13 patients). Nine patients in group 2 required IABP support postoperatively for 4.1 +/- 1.7 days. Only 2 patients in group 1 needed IABP postoperatively, and their IABPs were successfully removed on the first postoperative day. The preoperative IABP-supported patients had a shorter intensive care unit stay, 2.4 +/- 0.8 days compared with group 2, 4.5 +/- 2.2 days (p = 0.007), as well as a shorter hospital stay. The preoperative IABP treatment was found to be cost-effective. CONCLUSIONS: Preoperative treatment with IABP in high-risk redo CABG patients is an effective modality to prepare these patients to have their myocardial revascularization in an as nonischemic situation as possible, which resulted in a significantly lower hospital mortality, fewer instances of postoperative low cardiac output, and shorter stays in both the intensive care unit and the hospital.

Evaluation of preoperative intra-aortic balloon pump support in high risk coronary patients.

OBJECTIVE: The intra-aortic balloon pump (IABP) is an established additional support to pharmacological treatment of the failing heart after myocardial infarction, unstable angina and cardiac surgery. The effect of preoperative IABP in high risk patients was evaluated. METHODS: Between June 1994 and March 1996 all high risk patients for CABG (two or more of these criteria: Left ventricular ejection fraction (LVEF) < or = 40%, left main stem stenosis > or = 70%, REDO-CABG, unstable angina) were randomized into either of 3 groups: (1) IABP 1 day prior to surgery, (2) IABP 1-2 h prior to CPB and (3) no preoperative IABP, controls. EXCLUSION CRITERIA: cardiogenic shock preoperatively. Fifty-two patients have entered the study-group 1 (13 patients), group 2 (19 patients) and group 3 (20 patients). Preoperative patient characteristics and operative data revealed no group differences. There were 56% REDO's, unstable angina 59%, LVEF < or = 40%, 87% (34.0 +/- 11.6%) and left main stem stenosis in 35%. RESULTS: The CPB-time was shorter in groups 1 and 2 88.7 +/- 20.3 min than in group 3 105.5 +/- 26.8 min, P < 0.001, while ischemia time did not differ. Hospital mortality was higher in group 3, 25% vs. 6% (groups 1 and 2). Postoperative low cardiac output was seen in 12 patients (60%) in group 3 vs. 6 patients (19%) in groups 1 and 2, P < 0.05. Cardiac index increased significantly prior to CPB in groups 1 and 2. After CPB cardiac index was significantly higher in groups 1 and 2 compared to Group 3 and continued to increase. The IABP was removed after 3.1 +/- 1.0 days in group 3 vs. 1.3 +/- 0.6 days in groups 1 and 2, P < 0.001. In group 3, 11 patients required IABP postoperatively compared to only 4 patients in groups 1 and 2. ICU stay was shorter in groups 1 and 2--2.3 +/- 0.9 days vs. 3.5 +/- 1.1 days for group 3, P = 0.004. All patients received dopamin postoperatively, however in a lower dose in groups 1 and 2, 4.5 vs. 13.5 microg/kg/min. Dobutamine was added in 23% of the patients (group 1), 32% (group 2) and 95% (group 3). Adrenalin/amrinonum was required in 40% of the patients in group 3, 5% in group 2 and none in group 1. Group 1 patients had a better improvement of cardiac performance than group 2, while other parameters did not differ. Three months follow up of hospital survivors showed no group differences. CONCLUSIONS: The use of preoperative IABP in high risk patients lowers hospital mortality and shortens the stay in ICU, due to improved cardiac performance, compared to a controls. The procedure was cost-beneficial. One day preoperative IABP treatment improves cardiac performance more than 1-2 h preoperative IABP treatment, but does not significantly affect the outcome in terms of hospital mortality or postoperative morbidity.

The effect of preoperative intra-aortic balloon pump support in patients with coronary artery disease, poor left-ventricular function (LVEF < 40%), and hypertensive LV hypertrophy.

Poor left-ventricular function, hypertension, and left-ventricular hypertrophy in patients with coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG) are associated with increased operative risks. Between June 1994 and March 1996, 33 patients undergoing CABG, were randomized into 2 groups. One group (IABP group, n = 19) received IABP treatment on average for 2 hours prior to CPB, the other group (control group, n = 14) had no preoperative IABP, Cardiac performance was measured pre- and postoperatively by Swan-Ganz catheter. Mean age was 65 years and 90% were men. All patients had a preoperative LVEF < or = 40% (mean 32.6 +/- 11.1%), 3-vessel disease, established hypertension (WHO criteria), and LV hypertrophy (ventricular mass > or = 136 g/m2 [men] or > or = 110 g/m2 [women]). Ischemia time was similar in both groups while CPB-time was shorter in the IABP group, p < 0.05. There were no hospital deaths in the IABP group, but 3 in the control group suffered postoperative low cardiac output. Nine patients (64%) in the control group required IABP support postoperatively, but only 20% of the patients in the IABP group had a shorter ICU stay, 2.4 +/- 0.9 vs. 3.4 +/- 1.1 days, p < 0.01. Cardiac index increased significantly in the IABP group prior to CPB and was higher compared to control, p < 0.001. Five min after CBP cardiac index was higher in the IABP group than in the control group, p = 0.013, and continued to increase thereafter, while no further improvement was observed in controls. Preoperative IABP treatment in hypertensive patients with CAD, low LVEF and LV hypertrophy who are undergoing CABG is beneficial. An improved cardiac performance pre- and postoperatively was associated with a lower rate of hospital mortality and less postoperative morbidity, as well as shorter ICU stay. The treatment is cost-beneficial.

Plateletpheresis before redo CABG diminishes excessive blood transfusion.

BACKGROUND: Blood conservation remains an important element for patients undergoing cardiac operations with cardiopulmonary bypass. Preoperative platelet-rich plasma (PRP) harvest is an autologous blood conservation method. The efficacy of preoperative PRP harvest and post-cardiopulmonary bypass reinfusion on postoperative bleeding and need for postoperative blood transfusion was evaluated in patients undergoing redo coronary artery bypass grafting in a prospective, randomized manner. METHODS: All adult patients admitted for redo coronary artery bypass grafting entered into the study. The PRP harvest aim was 20% or more of the total estimated circulating platelets. Immediately preoperatively three sequestration cycles were performed. The PRP was reinfused after weaning from cardiopulmonary bypass. One hundred seven parameters/patient were recorded. There were 20 patients in the RPR group and 20 controls (without PRP harvest). RESULTS: Patient characteristics, operative data, and preoperative hematologic parameters did not differ between the groups. In the PRP group, the mean platelet count in the PRP was 864 +/- 139 x 10(3)/microL, and the platelet yield was 27% +/- 5% (range, 20% to 37%). The average total chest tube blood loss was 423 mL (PRP) compared with 1,462 mL (controls; p < 0.001). Fourteen patients in the control group required blood transfusions postoperatively compared with only 1 patient in the PRP group (p < 0.001). Postoperative fluid requirements were also significantly greater in the control group (p < 0.001). Postextubation gas exchange was significantly better in the PRP group compared with controls (p < 0.01). Postoperative ventilation time and intensive care stay were significantly shorter in patients in the PRP group. CONCLUSIONS: A preoperative PRP harvest of 20% or more of the total platelets and reinfusion of the PRP after cardiopulmonary bypass resulted in significantly less postoperative blood loss and decreased fluid and blood transfusion requirements compared with controls. Postextubation gas exchange, ventilation time, and time required in the intensive care unit were also better, and the method was found cost-effective.

Adult respiratory distress syndrome after cardiac surgery.

Adult respiratory distress syndrome, characterized by high permeability pulmonary oedema caused by endothelial cell damage, resulting in refractory hypoxemia, has a very high mortality. Cardiopulmonary bypass is said to be responsible for the development of adult respiratory distress syndrome after cardiac surgery. The present study was performed in order to identify predicting and aetiological factors of adult respiratory distress syndrome and multiple organ failure after cardiac surgery. Between January 1984 and December 1993, 3848 patients underwent cardiac surgery with cardiopulmonary bypass in the authors' institution, and were analysed in a retrospective manner. The operations performed were 3444 coronary artery bypass grafts (CABG), 267 valve and 137 combined (CABG + valve) procedures. The incidence of adult respiratory distress syndrome was 1.0% (38 of 3848) with an overall mortality rate of 68.4% (26 patients); 24 of these died from multiple organ failure. Multivariate regression analysis identified hypertension, current smoking, emergency surgery, preoperative New York Heart Association (NYHA) class 3 and 4, low postoperative cardiac output and left ventricular ejection fraction < 40% as significant, independent predictors for adult respiratory distress syndrome. Combined cardiac surgery and diffuse coronary disease were also significant predictors; cardiopulmonary bypass time was not. Thirty-six of the 38 patients that later developed adult respiratory distress syndrome had low postoperative cardiac output, 12 requiring intra-aortic balloon pump support. The remaining two had severe hypotension caused by postoperative bleeding. Twenty-six adult respiratory two had severe hypotension caused by postoperative bleeding. Twenty-six adult respiratory distress syndrome patients (68%) had confirmed gastrointestinal complication (e.g. intestinal ischaemia). Adult respiratory distress syndrome is a rare complication after cardiac surgery but is associated with a very high mortality. Preoperative predictors were identified. Cardiopulmonary bypass alone was not found to be an important factor. Postoperative low cardiac output leading to splanchnic hypoperfusion may be the most important single factor in developing adult respiratory distress syndrome after cardiac surgery.

Autologous platelet sequestration in patients undergoing coronary artery bypass grafting.

OBJECTIVES: Blood conservation remains an important issue for patients undergoing cardiac surgery with cardiopulmonary bypass. Platelet sequestration (PSQ) is an aggressive autologous blood conservation method, whose effectiveness is still debated. The main objective of the present study was to evaluate whether PSQ reduces postoperative blood transfusion requirements in patients undergoing coronary artery bypass grafting (CABG) and to determine if PSQ is a cost-effective blood conservation method. MATERIAL AND METHODS: All adult patients admitted for CABG entered the study. Exclusion criteria were: recent blood transfusion (<7 days), a platelet count of 150x10(3)/microl or less, hematocrit less than 35% and body weight 50 kg or less. The sequestration was aim 20% or more of the total platelet plasma volume. The sequestration protocol was three sequestration cycles performed just prior to surgery. The concentrated platelet portion was reinfused after weaning from the cardiopulmonary bypass. Hundred seven parameters/patients were recorded. Sixty patients entered the study; 30 in the PSQ group and 30 controls (CTR). RESULTS: Patient characteristics, operation data, preoperative hematology and coagulation parameters did not differ between the groups. In the PSQ group a mean of 433+/-34 ml concentrated platelet portion was collected. The mean platelet count in the concentrated platelet portion was 749+/-157x10(3)/microl, resulting in a platelet yield of 28+/-6% (2040%). The average total chest tube blood loss was 423 ml (PSQ) compared to 858 ml (CTR), p<0.001. A greater number of CTR patients required blood transfusion postoperatively (23) compared to PSQ (3), P<0.001, and fluid requirements were also significantly increased in the control group, P<0.001. No statistical differences in hematology and coagulation parameters between the groups were observed. The hospital mortality was low and the incidence of postoperative complications was few and without group differences. Post-extubation gas exchange was better in PSQ patients compared to CTR. CONCLUSIONS: A preoperative PSQ of a minimum 20% of the total platelet plasma volume resulted in significantly lower postoperative blood loss and fluid and blood transfusion requirements compared to controls. Post-extubation gas exchange was also better after PSQ. Only one patient did not tolerate the sequestration. No other adverse effects of the procedure were observed.