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BACKGROUND Veno-arterial extracorporeal membrane oxygenation therapy is a growing treatment modality for acute cardiorespiratory failure. Cardiac output monitoring during veno-arterial extracorporeal membrane oxygenation therapy remains challenging. This study aims to validate a new thermodilution technique during veno-arterial extracorporeal membrane oxygenation therapy using a pig model. METHODS Sixteen healthy pigs were centrally cannulated for veno-arterial extracorporeal membrane oxygenation, and precision flow probes for blood flow assessment were placed on the pulmonary artery. After chest closure, cold boluses of 0.9% saline solution were injected into the extracorporeal membrane oxygenation circuit, right atrium, and right ventricle at different extracorporeal membrane oxygenation flows (4, 3, 2, 1 l/min). Rapid response thermistors in the extracorporeal membrane oxygenation circuit and pulmonary artery recorded the temperature change. After calculating catheter constants, the distributions of injection volumes passing each circuit were assessed and enabled calculation of pulmonary blood flow. Analysis of the exponential temperature decay allowed assessment of right ventricular function. RESULTS Calculated blood flow correlated well with measured blood flow (r = 0.74, P < 0.001). Bias was -6 ml/min [95% CI ± 48 ml/min] with clinically acceptable limits of agreement (668 ml/min [95% CI ± 166 ml/min]). Percentage error varied with extracorporeal membrane oxygenation blood flow reductions, yielding an overall percentage error of 32.1% and a percentage error of 24.3% at low extracorporeal membrane oxygenation blood flows. Right ventricular ejection fraction was 17 [14 to 20.0]%. Extracorporeal membrane oxygenation flow reductions increased end-diastolic and end-systolic volumes with reductions in pulmonary vascular resistance. Central venous pressure and right ventricular ejection fractions remained unchanged. End-diastolic and end-systolic volumes correlated highly (r = 0.98, P < 0.001). CONCLUSIONS Adapted thermodilution allows reliable assessment of cardiac output and right ventricular behavior. During veno-arterial extracorporeal membrane oxygenation weaning, the right ventricle dilates even with stable function, possibly because of increased venous return. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Veno-arterial extracorporeal membrane oxygenation is an accepted rescue therapy for patients experiencing severe cardiac or pulmonary failure.Weaning from veno-arterial extracorporeal membrane oxygenation is important for determining next steps in patients' cardiopulmonary care. Assessment of right ventricular function during veno-arterial extracorporeal membrane oxygenation support and weaning is often done using echocardiography, but echocardiographic guidance provides challenges because right ventricular dimensions change with ventricular loading and may not be related to intrinsic right ventricular function. WHAT THIS ARTICLE TELLS US THAT IS NEW In 16 healthy pigs that received veno-arterial extracorporeal membrane oxygenation support via central cannulation, a novel adaptation of thermodilution cardiac output assessment provided reliable estimation of right ventricular cardiac output and right ventricular function.Future studies appear warranted to determine whether this method of modified thermodilution can be used to accurately assess right ventricular output and function during veno-arterial extracorporeal membrane oxygenation support.

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co2) or oxygen uptake (V̇o2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement −542 to 741 mL/min) with blood content V̇o2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias −395, limits of agreement −1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA −1,357 to 1,863 mL/min] for expired V̇o2 bias 482 [LoA −760 to 1,724 mL/min] for expired V̇co2) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

A hypothermic avalanche victim underwent, during extracorporeal warming from asystolic arrest, 3-dimensional transesophageal echocardiography. At 33°C core temperature, left ventricular ejection fraction had recovered, whereas myocardial strain still demonstrated significant dysfunction until 36°C. Deformation analysis seems more sensitive than global assessment during myocardial recovery from hypothermic cardiac arrest. (Level of Difficulty: Intermediate.), Graphical abstract

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.

Introduction Hypothermic circulatory arrest (HCA) in conjunction with selective antegrade cerebral perfusion (sACP) is frequently used for neuroprotection.(1) Nonetheless optimal sACP has only been investigated in animal studies.(2) The objective of this study was to determine sACP during HCA necessary to reach baseline tissue oxygenation as measured by near infrared spectroscopy (NIRS). Methods With local ethics committee approval, consecutive patients scheduled for elective aortic arch surgery in HCA were included in this prospective observational single center study. Bilateral sACP was institued by introducing perfusion catheters in the innominate and left carotid artery. The quality of sACP was monitored by bifrontal NIRS. Baseline NIRS were measured before anesthesia induction in the awake patient. NIRS values were recorded after initiation of HCA at sACP of 6, 8 and 10 milliliters (ml) per ideal body weight (kg) per minute (min). For comparison the mean of bifrontal NIRS in each patient was calculated for this interim analysis. Differences in NIRS between sACP flow rates were assessed by one-way ANOVA and Bonferroni t-test. A p Results Fifteen patients had complete datasets (4 female). NIRS was 62 (8) at baseline; 56 (11) at 6; 62 (11) at 8 and 63 (9) at 10 ml/kg/min sACP, respectively. ANOVA showed no significant differences between baseline and the three distinct sACP (p = 0.223). Bonferroni t-test indicated no differences between the different sACP and the baseline (all p>0.05). Duration of HCA was 12 (15) minutes. All patients were discharged after a length of hospital stay of 10 +/- 4 days. Three patients had new onset focal neurological deficits before discharge and three patients had postoperative delirium. Discussion SACP of 6-10ml is the range often used in centers of aortic arch surgery. (1) In an animal-model, the lower threshold of 6ml/kg/min was confirmed recently, since venous saturation decreased markedly when sACP was lowered below this sACP.(2) Our data support this finding in humans as sACP f of 6 ml/kg/min is sufficient to reach baseline NIRS values. A further increase, e.g., to 8 or 10 ml/kg/min, is not associated with an even better NIRS. The data suggest that sufficient frontal brain oxygenation can be achieved with a relatively low sACP flow rate in HCA.

BACKGROUND:Asialoglycoprotein receptor 1 (ASGR1) mediates capture and phagocytosis of platelets in pig to primate liver xenotransplantation. However thrombocytopenia is also observed in xenotransplantation or xenoperfusion of other porcine organs than liver. We therefore assessed ASGR1 expression as well as ASGR1 mediated xenogeneic platelet phagocytosis in vitro and ex vivo on porcine aortic femoral arterial and liver sinusoidal endothelial cells (PAEC/PFAEC/PLSEC). METHODS:Porcine forelimbs were perfused with whole heparinized human or autologous pig blood. Platelets were counted at regular intervals. Pig limb muscle and liver as well as PAEC/PFAEC/PLSEC were characterized for ASGR1 expression. In vitro PAEC cultured on microcarrier beads and incubated with non anticoagulated human blood were used to study binding of human platelets and platelet white blood cell aggregation. Carboxyfluorescein diacetate succinimidyl ester labeled human platelets were exposed to PAEC/PFAEC/PLSEC and analyzed for ASGR1 mediated phagocytosis. RESULTS:Human platelet numbers decreased from 102 {\textpm} 33 at beginning to 13 {\textpm} 6 {\texttimes} 10/µL (P < 0.0001) after 10 minutes of perfusion whereas no significant decrease of platelets was seen during autologous perfusions (171 {\textpm} 26 to 122 {\textpm} 95 {\texttimes} 10/µL). The PAEC PFAEC and PLSEC all showed similar ASGR1 expression. In vitro no correlation was found between reduction in platelet count and platelet white blood cell aggregation. Phagocytosis of human carboxyfluorescein diacetate succinimidyl ester labeled platelets by PAEC/PFAEC/PLSEC peaked at 15 minutes and was inhibited (P < 0.05 to P < 0.0001) by rabbit anti ASGR1 antibody and asialofetuin. CONCLUSIONS:The ASGR1 expressed on aortic and limb arterial pig vascular endothelium plays a role in binding and phagocytosis of human platelets. Therefore ASGR1 may represent a novel therapeutic target to overcome thrombocytopenia associated with vascularized pig to primate xenotransplantation.

BACKGROUND Besides α1,3-galactosyltransferase gene (GGTA1) knockout, several transgene combinations to prevent pig-to-human xenograft rejection are currently being investigated. In this study, the potential of combined overexpression of human CD46 and HLA-E to prevent complement- and NK-cell-mediated xenograft rejection was tested in an ex vivo pig-to-human xenoperfusion model. METHODS α1,3-Galactosyltransferase knockout heterozygous, hCD46/HLA-E double transgenic (transgenic) as well as wild-type pig forelimbs were ex vivo perfused with whole, heparinized human and autologous pig blood, respectively. Blood samples were analyzed for the production of porcine and/or human inflammatory cytokines as well as complement activation products. Biopsy samples were examined for deposition of human and porcine C3b/c, C4b/c, and C6 as well as CD62E (E-selectin) and CD106 (VCAM-1) expression. Apoptosis was measured in the porcine muscle tissue using TUNEL assays. Finally, the formation of thrombin-antithrombin (TAT) complexes was measured in EDTA plasma samples. RESULTS No hyperacute rejection was seen in this model. Extremity perfusions lasted for up to 12 h without increase in vascular resistance and were terminated due to continuous small blood losses. Plasma levels of porcine cytokines IL1β, IL-6, IL-8, IL-10, TNF-α, and MCP-1 as well as human complement activation markers C3a (P = 0.0002), C5a (P = 0.004), and soluble C5b-9 (P = 0.03) were lower in blood perfused through transgenic as compared to wild-type limbs. Human C3b/c, C4b/c, and C6 as well as CD62E and CD106 were deposited in tissue of wild-type limbs, but significantly lower levels (P

Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation. We used C1-easterase inhibitor (C1-INH) in this study because of its known inhibitory effects on the activation of the complement, coagulation and kinin cascades. Forelimbs of 8 large white pigs were amputated, subjected to ischemia, and then reperfused with autologous whole blood. All limbs were exposed to 9h of cold ischemia at 4°C. After 2h of cold ischemia the limbs were either perfused with of C1-INH (1U/ml in hydroxyethyl starch, n=8) or hydroxyethyl starch alone (n=7). After completion of the 9-h ischemia period, all limbs were ex vivo perfused with heparinized autologous whole blood for 12h using a pediatric heart lung machine to simulate in vivo revascularization. Our results show that I/R injury in the control group led to a significant elevation of tissue deposition of IgG and IgM, complement C3b/c, C5b-9 and MBL. Also, activation of the kinin system was significantly increased, namely bradykinin in plasma, and expression of bradykinin receptors 1 and 2 in tissue. In addition, markers for endothelial integrity like expression of CD31, VE-cadherin and heparan sulfate proteoglycans were decreased in reperfused tissue. Limb I/R injury also led to activation of the coagulation cascade with a significant elevation of fibrin and thrombin deposition and increased fibrinogen-like protein-2 expression. C1-INH treated limbs showed much less activation of plasma cascades and better protection of endothelial integrity compared to the reperfused control limbs. In conclusion, the use of the cytoprotective drug C1-INH significantly reduced I/R injury by protecting the vascular endothelium as well as the muscle tissue from deposition of immunoglobulins, complement and fibrin.

Background. Natural IgM containing anti Gal antibodies initiates classic pathway complement activation in xenotrans plantation. However in ischemia reperfusion injury IgM also induces lectin pathway activation. The present study was therefore focused on lectin pathway as well as interaction of IgM and mannose binding lectin (MBL) in pig to human xenotransplantation models. Methods. Activation of the different complement pathways was assessed by cell enzyme linked immunosorbent assay using human serum on wild type (WT) and > galactosyl transferase knockout (GalTKO)/hCD46 transgenic porcine aortic endothelial cells (PAEC). Colocalization of MBL/MASP2 with IgM C3b/c C4b/c and C6 was investigated by immunofluorescence in vitro on PAEC and ex vivo in pig leg xenoperfusion with human blood. Influence of IgM on MBL binding to PAEC was tested using IgM depleted/repleted and anti Gal immunoabsorbed serum. Results. Activation of all the three complement pathways was observed in vitro as indicated by IgM C1q MBL and factor Bb deposition on WT PAEC. MBL deposition colocalized with MASP2 (Manders’ coefficient [3D] r2=0.93) C3b/c (r2=0.84) C4b/c (r2=0.86) and C6 (r2=0.80). IgM colocalized with MBL (r2=0.87) and MASP2 (r2=0.83). Human IgM led to dose dependently increased deposition of MBL C3b/c and C6 on WT PAEC. Colocalization of MBL with IgM (Pearson’s coefficient [2D] rp2=0.88) C3b/c (rp2=0.82) C4b/c (rp2=0.63) and C6 (rp2=0.81) was also seen in ex vivo xenoperfusion. Significantly reduced MBL deposition and complement activation was observed on GalTKO/hCD46 PAEC. Conclusion. Colocalization of MBL/MASP2 with IgM and complement suggests that the lectin pathway is activated by human anti Gal IgM and may play a pathophysiologic role in pig to human xenotransplantation. Keywords: Mannose binding lectin Complement pathways Natural antibody Xenotransplantation Porcine aortic endothelial cells.

OBJECTIVE To analyse the results after elective open total aortic arch replacement. METHODS We analysed 39 patients (median age 63 years, median logistic EuroSCORE 18.4) who underwent elective open total arch replacement between 2005 and 2012. RESULTS In-hospital mortality was 5.1% (n = 2) and perioperative neurological injury was 12.8% (n = 5). The indication for surgery was degenerative aneurysmal disease in 59% (n = 23) and late aneurysmal formation following previous surgery of type A aortic dissection in 35.9% (n = 14); 5.1% (n = 2) were due to anastomotical aneurysms after prior ascending repair. Fifty-nine percent (n = 23) of the patients had already undergone previous proximal thoracic aortic surgery. In 30.8% (n = 12) of them, a conventional elephant trunk was added to total arch replacement, in 28.2% (n = 11), root replacement was additionally performed. Median hypothermic circulatory arrest time was 42 min (21-54 min). Selective antegrade cerebral perfusion was used in 95% (n = 37) of patients. Median follow-up was 11 months [interquartile range (IQR) 1-20 months]. There was no late death and no need for reoperation during this period. CONCLUSIONS Open total aortic arch replacement shows very satisfying results. The number of patients undergoing total arch replacement as a redo procedure and as a part of a complex multisegmental aortic pathology is high. Future strategies will have to emphasize neurological protection in extensive simultaneous replacement of the aortic arch and adjacent segments.

Background Revascularization of amputated extremities after prolonged ischemia is complicated by reperfusion injury. We assessed ischemia/reperfusion (I/R) injury of porcine extremities after prolonged preservation using extracorporeal circulation (ECC). Methods Forelimbs of 32 pigs were divided into four groups based on ischemia times: group I: 6 h, group II: 12 h, group III: 0 h plus replantation, and group IV: 6 h plus replantation. Limbs were perfused with autologous blood using ECC for 12 h except group II with only 5 h perfusion. Limbs from groups III and IV were heterotopically replanted with a 7-d follow-up. Contralateral limbs served as controls in all groups. Tissue, plasma, and serum were analyzed for the extent of I/R injury. Results No significant differences in tissue wet/dry ratios were found within or between groups. This finding was confirmed by histology, except for an increased damage in group IV muscles compared with baseline (P = 0.016). Complement C3 deposition was only increased in group IV muscle (P = 0.031), group II nerves (P = 0.046), and group II vessels (P = 0.037). Group IV muscle and nerve tissues were the only ones with significant IgM antibody deposition (P = 0.031) at end of perfusion. Values were normal again after replantation. Reduced complement activity and elevated IL-6, IL-8, MCP-1, VEGF, PDGF-bb, bFGF, and complement split products were found during perfusion but were normal again after replantation. Staining for heparin sulfate proteoglycans and von Willebrand factor confirmed minimal activation of endothelial cells. Conclusion The results demonstrate that prolonged limb preservation using ECC has minimal impact on I/R-induced tissue injury. Extracorporeal perfusion is a potential limb-preserving technique encouraging further studies for use in limb revascularization.

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase-related rate of high-intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre-defined procedural phases in SAVR using MiECC or CECC with (+F) or without (-F) an oxygenator with integrated arterial filter. Forty-eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19-2.56). This was due to different HITS rates in procedural phases from aortic cross-clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC-F generated a higher HITS rate than CECC+F (P = 0.005), CECC-F (P = 0.05) in phase 4, and CECC-F (P = 0.03) in phase 5, respectively. In open-heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.

Stereology is an essential method for quantitative analysis of lung structure. Adequate fixation is a prerequisite for stereological analysis to avoid bias in pulmonary tissue, dimensions and structural details. We present a technique for in situ fixation of large animal lungs for stereological analysis, based on closed loop perfusion fixation.Twenty anesthetized ventilated pigs (30 ± 3 kg) underwent cannulation of the pulmonary artery and ligation of the right hilus. Following circulatory arrest a continuous positive pressure of 12 mbar was applied to the airways and lung perfusion started with the fixative solution (1.5% paraformaldehyde; 1.5% glutaraldehyde in 0.15 M HEPES). In five animals, a single-pass perfusion technique was performed, in 15 subsequent animals, the closed-loop technique was applied. Afterwards, lungs were removed, externally postfixed in the recycled fixative solution, and stored at 4 °C. Fifteen lung specimens underwent stereological analysis with volume estimation and subsequent systematic uniform random sampling for light and electron microscopic analysis.Singlepass perfusion did not result in satisfactory fixation. Left lung closed loop perfusion rate was 0.5-0.7 L/min with total median [min-max] perfusion time of 15 min (11-19). Perfusion pressure was 15 mm Hg (9-33). Subsequent lung analysis revealed well-preserved cell and tissue ultrastructure.The closed loop perfusion technique represents a valuable and reproducible fixation method in large animal models. Pressure controlled fixation perfusion results in high-quality preservation of in situ parenchymal architecture of lungs with or without injury, which is ideally suited for quantitative assessment of lung structure by stereology.

Background— The goal of this study was to determine whether advanced age affects mortality and incidence of neurological injury in patients undergoing surgical repair with hypothermic circulatory arrest in acute and chronic thoracic aortic pathology. Methods and Results— A university center audit was done of 523 consecutive patients (median age, 64 years; interquartile range, 56–71 years) between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients) was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2% ( P P =0.002). Multivariable regression analysis revealed hypothermic circulatory arrest >40 minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60–11.06; P =0.004) and redo surgery (OR, 3.44; 95% CI, 1.11–10.64; P =0.03) but not age (OR, 1.98; 95% CI, 0.73–5.38; P =0.18) as independent predictor of mortality. Emergency surgery (OR, 3.27; 95% CI, 1.31–8.15; P =0.01) and extracardiac arteriopathy (OR, 2.38; 95% CI, 1.26–4.50; P =0.008) but not age (OR, 1.80; 95% CI, 0.93–3.48; P =0.08) were independent predictors of neurological injury. Conclusions— Age is not associated with increased risk for mortality and neurological injury in patients undergoing surgical repair for acute and chronic thoracic aortic pathology with hypothermic circulatory arrest. Extended hypothermic circulatory arrest times, reflecting the extent of disease, and redo surgery predict mortality, whereas emergency surgery and extracardiac arteriopathy predict neurological injury.

Background Many dissections seem to also have a retrograde component. The aim of the study was to evaluate different sites of primary entry tears and the propagation of the dissecting membrane, antegrade and retrograde, in an experimental model of acute type B aortic dissection. Methods The entire thoracic aortic aorta including the supraaortic branches was harvested from 26 adult pigs. An intimal tear of 15 mm was created by contralateral incisions sites 20 mm downstream the origin of the left subclavian artery. In 13 cases the dissection was created at the concavity and in 13 cases at the convexity. The aortic annulus was then sewn into a silicon ring of a driving chamber. The distal aorta was connected to a tubing with adjustable resistance elements. The circulation was driven by the pneumatically driven Vienna heart to mimic aortic flow and pressure. Results Mean circulation time was 64 ± 45 minutes. A mean pressure of 152 ± 43 mm Hg and a mean flow of 4.5 ± 1.0 L/minute were reached. The median antegrade propagation length of the dissecting membrane was 65 mm. The median retrograde propagation length in primary entry tears at the convexity was 20 mm and was stopped by the left subclavian artery. In aortas with the primary entry tear at the concavity, median retrograde propagation length was 21 mm extending up to the ascending aorta in 16%. Conclusions In this experimental model of acute type B aortic dissection, we confirmed that many type B dissections do also have a retrograde component. At the convexity, this component is stopped by the left subclavian artery as an anatomic barrier. At the concavity, the propagation of the dissecting membrane may extend up to the ascending aorta and may therefore cause retrograde type A dissection. These findings may substantiate clinical need for treatment of type B dissections with a primary entry tear at the concavity.

Objective: To measure surrogate markers of coagulation activation as well as of the systemic inflammatory response in patients undergoing primary elective coronary artery bypass grafting (CABG) using either the so-called Smart suction device or a continuous autotransfusion system (C.A.T.S.®). Methods: Fifty-eight patients being operated with a miniaturized circuit (minimal extracorporeal circuit, MECC) were prospectively randomized to using a so-called Smart suction device or a routine continuous autotransfusion system (C.A.T.S.®) for collection of mediastinal shed blood. The coagulation response was measured by thrombin-antithrombin complex (TAT) and D-dimer. The inflammatory response was measured by Interleukin 6 (IL-6) and complement factor 3a (C3a) at three different time points, before surgery, 2h after surgery, as well as 18h after surgery. Results: No serious adverse cardiovascular event was observed. Serum levels of TAT significantly differed between both groups 2h after surgery (Smart suction 16.12±13.51μgl−1 vs C.A.T.S® 9.83±7.81μgl−1, p=0.040) and returned to baseline values after 18h in both groups. Serum levels of D-dimer showed a corresponding pattern with a peak 2h after surgery (Smart suction 1115±1231ngml−1 vs C.A.T.S.® 507±604ngml−1, p=0.025). IL-6 levels also significantly differed between both groups 2h after surgery (Smart suction 186±306pgml−1 vs C.A.T.S.® 82±71pgml−1, p=0.072). No significant changes in serum levels of C3a over time could be observed. Conclusions: Despite no differences in the clinical course of patients with either Smart suction or C.A.T.S.® being observed, surrogate markers of coagulation and inflammation seem to be less pronounced in patients where cardiotomy blood is not being directly reinfused. As such, C.A.T.S.® should be preferred in routine CABG, as long as no extensive volume substitution is anticipated

Background Successful extremity transplantations and replantations have to be performed within 6 h of amputation to avoid irreversible tissue loss. This study investigates ex vivo the technical feasibility and the limb preservation potential of extracorporeal whole blood perfusion in a porcine model. Methods Forelimbs of eight large white pigs were divided into paired groups: I perfusion group, II contralateral cold ischemia controls. In group I axillary arteries and veins were cannulated and perfusion with anticoagulated autologous blood was performed for 12 h; O2, CO2, Hb, lactate, potassium, pH, and muscle contractility were monitored. Tissue biopsies were examined by histology and immunofluorescence. Group II was stored at 4°C. Results Continuous limb perfusion could be performed in all extremities of group I for 12 h. pH was maintained normal and potassium controlled with insulin and glucose. Lactate levels increased initially during perfusion due to the lack of a metabolizing liver. Muscle stimulation was possible throughout the entire perfusion, whereas a complete loss of response was noted in cold ischemia controls. Minor tissue damage was observed histologically and by immunofluorescence in group I, whereas the samples of group II were apparently preserved with the exception of a loss of endothelial heparan sulfate. Conclusions The tissue preserving potential and the feasibility of extremity perfusion using common extracorporeal blood circulation techniques was demonstrated in this ex vivo study. The results encourage further investigations in prolonged perfusion followed by limb replantation. This approach harbors promising clinical potential for extremity preservation in extremity transplantation and replantation.

Objective: This study investigated the use of a new concept of mitral valve reconstruction using a novel device to stent the posterior mitral leaflet in combination with semicircular annuloplasty. Modern mitral valve repair is an accepted modality and a routine procedure for treatment of degenerative mitral valve insufficiency. One of the most common mechanisms of mitral valve insufficiency is leaflet prolapse. In the majority of cases the posterior leaflet is dysfunctional and therapeutic reconstruction of the PII flail leaflet segment involves quadrangular resection which is usually combined to mitral annuloplasty with a ring. A new time-saving concept of mitral valve reconstruction by stenting the posterior mitral leaflet in combination with semicircular annuloplasty is presented. Methods: The new mitral valve reconstruction device (Shelhigh MitroFast(tm), Shelhigh, Inc. TM , Union, NJ, USA) was implanted in four adult sheep. It is constructed as an annuloplasty ring in combination with a posterior leaflet stent. The device has the shape of a closed posterior leaflet and forms a “buttress” against which the anterior leaflet can coapt. Results: Every implantation of a MitroFast TM device could be performed in less than 30 minutes. After implantation of the device, all animals could be successfully weaned from CPB. Invasively measured left atrial pressure was below 12 mm Hg in all animals. After chest closure, transoesophageal echocardiography revealed a competent mitral valve in all animals, without any inflow restriction in three animals, and suspected mild stenosis in one animal. Conclusions: In this experimental model, implantation of the newly designed annuloplasty ring with stenting the posterior mitral leaflet avoids extensive and time-consuming reconstructive surgery on a flail posterior leaflet. Implantation of the device resulted in favorable short-term hemodynamic effects. Implantation technique of the device is simple, the potential for minimal invasive implantation of a conceptual similar device will be further investigated. INTRODUCTON Modern mitral valve repair with implantation of a prosthetic ring was first performed in the late 1960s by Carpentier [Carpentier 1969]. Results following mitral valve repair are superior [Gillinov 2001, Grossi 2001] to those of standard mitral valve replacement without saving the subvalvular apparatus. Therefore repair is nowadays a routine procedure for treatment of degenerative mitral valve insufficiency. One of the most common mechanisms of mitral valve insufficiency is leaflet prolapse due to chordal elongation, ruptured chordae or papillary muscle. In the majority of cases the middle part (P II) of the posterior leaflet is dysfunctional and reconstruction of the PII flail leaflet segment involves quadrangular resection. This is usually combined to mitral annuloplasty with a ring. Resection of the middle segment is performed and the resulting gap sutured with single interrupted sutures to reconstruct a competent valve. Echocardiographic assessment following mitral valve repair commonly shows a rather shrinked and remaining posterior leaflet with decreased motility. We investigated a new concept of mitral valve reconstruction using the Shelhigh MitroFast(tm) (Shelhigh, Inc. TM , Union, NJ, USA) device to stent the posterior mitral leaflet in combination with semicircular annuloplasty. This technique allows substantial time saving compared to a classical reconstruction procedure.