Medico-legal autopsy in postoperative hemodynamic collapse following coronary artery bypass surgery

Sudden unexpected postoperative hemodynamic collapse with a high mortality develops in 1–3% of patients undergoing coronary artery bypass surgery (CABG). The contribution of surgical graft complications to this serious condition is poorly known and their demonstration at autopsy is a challenging task. Isolated CABG was performed in 8,807 patients during 1988–1999. Of the patients, 76 (0.9%) developed sudden postoperative hemodynamic collapse resulting in subsequent emergency reopening of the median sternotomy and open cardiac massage. Further emergency reoperation could be performed in 62 (82%) whereas 14 patients died prior to reoperation and a further 21 did not survive the reoperation or died a few days later. All 35 (46%) patients who did not survive were subjected to medico-legal autopsy combined with postmortem cast angiography. By combining clinical data with autopsy and angiography data, various types of graft complications were observed in 27 (36%, 1.3 per patient) of the 76 patients with hemodynamic collapse. There were no significant differences in the frequency (33 vs. 40%) or number of complicated grafts per patient (1.2 vs. 1.4) between those who survived reoperation and who did not. Autopsy detected 25 major and minor findings not diagnosed clinically. Postmortem cast angiography visualized 2 graft twists not possible to detect by autopsy dissection only. Surgical graft complications were the most frequent single cause for sudden postoperative hemodynamic collapse in CABG patients leading to a fatal outcome in almost half of the cases. Postmortem angiography improved the accuracy of autopsy diagnostics of graft complications

Possible extracardiac predictors of aortic dissection in Marfan syndrome

BACKGROUND: According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS. METHODS: A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-beta (TGF-beta) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed. RESULTS: Among patients with aortic dissection, TGF-beta serum level was elevated (43.78 +/- 6.51 vs. 31.64 +/- 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2alpha = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group. CONCLUSIONS: We found three easily measurable parameters (striae atrophicae, TGF-beta serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR

Development and characterisation of a large diameter decellularised vascular allograft

The aims of this study were to develop a biological large diameter vascular graft by decellularisation of native human aorta to remove the immunogenic cells whilst retaining the essential biomechanical, and biochemical properties for the ultimate benefit of patients with infected synthetic grafts. Donor aortas (n = 6) were subjected to an adaptation of a propriety decellularisation process to remove the cells and acellularity assessed by histological analysis and extraction and quantification of total DNA. The biocompatibility of the acellular aortas was determined using standard contact cytotoxicity tests. Collagen and denatured collagen content of aortas was determined and immunohistochemistry was used to determine the presence of specific extracellular matrix proteins. Donor aortas (n = 6) were divided into two, with one half subject to decellularisation and the other half retained as native tissue. The native and decellularised aorta sections were then subject to uniaxial tensile testing to failure [axial and circumferential directions] and suture retention testing. The data was compared using a paired t-test. Histological evaluation showed an absence of cells in the treated aortas and retention of histoarchitecture including elastin content. The decellularised aortas had less than 15 ng mg¯¹ total DNA per dry weight (mean 94% reduction) and were biocompatible as determined by in vitro contact cytotoxicity tests. There were no gross changes in the histoarchitecture [elastin and collagen matrix] of the acellular aortas compared to native controls. The decellularisation process also reduced calcium deposits within the tissue. The uniaxial tensile and suture retention testing revealed no significant differences in the material properties (p > 0.05) of decellularised aorta. The decellularisation procedure resulted in minimal changes to the biological and biomechanical properties of the donor aortas. Acellular donor aorta has excellent potential for use as a large diameter vascular graft

The Influence of pCO2 and Temperature on Gene Expression of Carbon and Nitrogen Pathways in Trichodesmium IMS101

Growth, protein amount, and activity levels of metabolic pathways in Trichodesmium are influenced by environmental changes such as elevated pCO2 and temperature. This study examines changes in the expression of essential metabolic genes in Trichodesmium grown under a matrix of pCO2 (400 and 900 µatm) and temperature (25 and 31°C). Using RT-qPCR, we studied 21 genes related to four metabolic functional groups: CO2 concentrating mechanism (bicA1, bicA2, ccmM, ccmK2, ccmK3, ndhF4, ndhD4, ndhL, chpX), energy metabolism (atpB, sod, prx, glcD), nitrogen metabolism (glnA, hetR, nifH), and inorganic carbon fixation and photosynthesis (rbcL, rca, psaB, psaC, psbA). nifH and most photosynthetic genes exhibited relatively high abundance and their expression was influenced by both environmental parameters. A two to three orders of magnitude increase was observed for glnA and hetR only when both pCO2 and temperature were elevated. CO2 concentrating mechanism genes were not affected by pCO2 and temperature and their expression levels were markedly lower than that of the nitrogen metabolism and photosynthetic genes. Many of the CO2 concentrating mechanism genes were co-expressed throughout the day. Our results demonstrate that in Trichodesmium, CO2 concentrating mechanism genes are constitutively expressed. Co-expression of genes from different functional groups were frequently observed during the first half of the photoperiod when oxygenic photosynthesis and N2 fixation take place, pointing at the tight and complex regulation of gene expression in Trichodesmium. Here we provide new data linking environmental changes of pCO2 and temperature to gene expression in Trichodesmium. Although gene expression indicates an active metabolic pathway, there is often an uncoupling between transcription and enzyme activity, such that transcript level cannot usually be directly extrapolated to metabolic activity

Transapical, off-pump, removal of the native aortic valve. A large animal study

ObjectiveThis study evaluates the feasibility of off-pump native aortic valve removal in preparation for transapical aortic valve replacement. Off-pump aortic valve replacement is performed by balloon predilatation of the native valve followed by insertion of a stented prosthesis. In patients with calcified annuli and cusps, particulate embolization, suboptimal prosthesis sizing, and perivalvular leaks may occur. Therefore, native valve removal may improve outcomes after transapical aortic valve replacement.MethodsThe aortic cusps were sequentially removed from 10 pigs in an off-pump procedure. A temporary valve was inserted percutaneously into the ascending aorta to prevent aortic regurgitation. The electrocardiogram, coronary blood flow, and arterial, left atrial, and ventricular pressures were continuously monitored.ResultsRemoval of the aortic cusps caused a drop in diastolic arterial pressure and its equalization with left ventricular diastolic pressure. Systolic pressure decreased by 13.5%. Left atrial pressure increased by 86.0%. Coronary blood flow decreased by 39.9% and its pattern changed from mostly diastolic to mostly systolic. Electrocardiographic signs of ischemia appeared almost immediately. Percutaneous insertion of a temporary valve in the ascending aorta increased diastolic pressure and caused a tendency toward echocardiographic normalization.ConclusionsAortic valve removal in a healthy beating heart causes acute massive aortic regurgitation, hemodynamic instability, and the rapid onset of myocardial ischemia. Reduction of left ventricular volume overload, by placement of a temporary valve in the ascending aorta, mitigates myocardial distress, helps stabilize hemodynamic parameters, and may be a useful tool to allow surgical manipulations of the aortic valve and annulus during transapical aortic valve replacement procedures