Microdialysis of the rectus abdominis muscle for early detection of impending abdominal compartment syndrome

Objective: To investigate whether microdialysis is capable of assessing metabolic derangements during intra-abdominal hypertension (IAH), and whether monitoring of the rectus abdominis muscle (RAM) by microdialysis represents areliable approach in the early detection of organ dysfunctions in abdominal compartment syndrome (ACS). Design: Prospective, randomized, controlled animal study. Setting: University animal research facility. Subjects: Fifteen isoflurane-anesthetized and mechanically ventilated Sprague-Dawley rats. Interventions: IAH of 20 mmHg was induced for 3 h and followed by decompression and reperfusion for another 3-h period (n = 10). Five sham-operated animals served as controls. Microdialysis was performed in the anterior gastric wall, liver, kidney, and RAM. The anterior cervical muscles served as distant reference. Glucose, lactate, pyruvate, and glycerol was analyzed throughout the 6-h experiment. Measurements and main results: Prolonged IAH induced significant cardiopulmonary dysfunction and persistent abdominal organ injury. Microdialysis revealed asignificant increase of lactate/pyruvate and glycerol in kidney, intestine and liver, indicating ischemia, energy failure, and cell membrane damage. In addition, at 3 h IAH glucose was significantly decreased in all organs studied. The distant reference did not show any alteration of lactate/pyruvate, glycerol, and glucose over the entire 6-h observation period. In contrast to the other organs, microdialysis of the RAM showed an early and more pronounced increase of lactate, lactate/pyruvate and glycerol already at 1 h IAH. It is noteworthy that lactate, glycerol, and glucose did not completely recover upon decompression of IAH. Conclusions: Our data suggest that continuous microdialysis in the RAM may represent apromising tool for early detecting IAH-induced metabolic derangement

Angiogenesis in tissue engineering : Breathing life into constructed tissue substitutes

Long-term function of three-dimensional (3D) tissue constructs depends on adequate vascularization after implantation. Accordingly, research in tissue engineering has focused on the analysis of angiogenesis. For this purpose, 2 sophisticated in vivo models (the chorioallantoic membrane and the dorsal skinfold chamber) have recently been introduced in tissue engineering research, allowing a more detailed analysis of angiogenic dysfunction and engraftment failure. To achieve vascularization of tissue constructs, several approaches are currently under investigation. These include the modification of biomaterial properties of scaffolds and the stimulation of blood vessel development and maturation by different growth factors using slow-release devices through pre-encapsulated microspheres. Moreover, new microvascular networks in tissue substitutes can be engineered by using endothelial cells and stem cells or by creating arteriovenous shunt loops. Nonetheless, the currently used techniques are not sufficient to induce the rapid vascularization necessary for an adequate cellular oxygen supply. Thus, future directions of research should focus on the creation of microvascular networks within 3D tissue constructs in vitro before implantation or by co-stimulation of angiogenesis and parenchymal cell proliferation to engineer the vascularized tissue substitute in situ

Extracorporeal Circulation During Lung Transplantation Procedures: a Meta-Analysis

Extracorporeal circulation (ECC) is an invaluable tool in lung transplantation (lutx). More than the past years, an increasing number of centers changed their standard for intraoperative ECC from cardiopulmonary bypass (CPB) to extracorporeal membrane oxygenation (ECMO) - with differing results. This meta-analysis reviews the existing evidence. An online literature research on Medline, Embase, and PubMed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial ECMO (VA-ECMO) resulted in better outcomes compared with CPB. Six papers - all observational studies without randomization - were included in the analysis. All were considered to have serious bias caused by heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells (RBCs) with an average mean difference of -0.46 units 95{\%} CI = -3.72, 2.80, fresh-frozen plasma with an average mean difference of -0.65 units 95{\%} CI = -1.56, 0.25, platelets with an average mean difference of -1.72 units 95{\%} CI = -3.67, 0.23). Duration of ventilator support with an average mean difference of -2.86 days 95{\%} CI = -11.43, 5.71 and intensive care unit (ICU) length of stay with an average mean difference of -4.79 days 95{\%} CI = -8.17, -1.41 were shorter in ECMO patients. Extracorporeal membrane oxygenation treatment tended to be superior regarding 3 month mortality (odds ratio = 0.46, 95{\%} CI = 0.21-1.02) and 1 year mortality (odds ratio = 0.65, 95{\%} CI = 0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation, and underlying disease) influenced differences. These data indicate a benefit of the intraoperative use of ECMO as compared with CPB during lung transplant procedures regarding short-term outcome (ICU stay). There was no statistically significant effect regarding blood transfusion needs or long-term outcome. The superiority of ECMO in lutx patients remains to be determined in larger multi-center randomized trials

Identifying patients at risk: multi-centre comparison of HeartMate 3 and HeartWare left ventricular assist devices

Aims: Since the withdrawal of HeartWare (HVAD) from the global market, there is an ongoing discussion if and which patients require prophylactically exchange for a HeartMate 3 (HM3). Therefore, it is important to study outcome differences between HVAD and HM3 patients. Because centres differ in patient selection and standard of care, we performed a propensity score (PS)-based study including centres that implanted both devices and aimed to identify which HVAD patients are at highest risk. Methods and results: We performed an international multi-centre study (n = 1021) including centres that implanted HVAD and HM3. PS-matching was performed using clinical variables and the implanting centre. Survival and complications were compared. As a sensitivity analysis, PS-adjusted Cox regression was performed. Landmark analysis with conditional survival >2 years was conducted to evaluate long-term survival differences. To identify which HVAD patients may benefit from a HM3 upgrade, Cox regression using pre-operative variables and their interaction with device type was performed. Survival was significantly better for HM3 patients (P 2 years after implantation (P = 0.03). None of the pre-operative variable interactions in the Cox regression were significant. Conclusions: HM3 patients have a significantly better survival and a lower incidence of ischaemic strokes and pump thrombosis than HVAD patients. This survival difference persisted after 2 years of implantation. Additional research using post-operative variables is warranted to identify which HVAD patients need an upgrade to HM3 or expedited transplantation

Lower frequency routine surveillance endomyocardial biopsies after heart transplantation

In heart transplantation (HTx) patients, routine surveillance endomyocardial biopsies (rsEMB) are recommended for the detection of early cardiac allograft rejection. However, there is no consensus on the optimal frequency of rsEMB. Frequent rsEMB have shown a low diagnostic yield in the new era of potent immunosuppressive regimen. Efficacy and safety of lower frequency rsEMB have not been investigated so far. In this retrospective, single centre, observational study we evaluated 282 patients transplanted between 2004 and 2014. 218 of these patients were investigated by rsEMB and symptom-triggered EMB (stEMB). We evaluated EMB results, complications, risk factors for rejection, survival 1 and 5 years as well as incidence of cardiac allograft vasculopathy (CAV) 3 years after HTx. A mean of 7.1 +/- 2.5 rsEMB were conducted per patient within the first year after HTx identifying 7 patients with asymptomatic and 9 patients with symptomatic acute rejection requiring glucocorticoide pulse therapy. Despite this relatively low frequency of rsEMB, only 6 unscheduled stEMB were required in the first year after HTx leading to 2 additional treatments. In 6 deaths among all 282 patients (2.1%), acute rejection could not be ruled out as a potential underlying cause. Overall survival at 1 year was 78.7% and 5-year survival was 74%. Incidence of CAV was 17% at 3-year follow-up. Morbidity and mortality of lower frequency rsEMB are comparable with data from the International Society for Heart and Lung Transplantation (ISHLT) registry. Consensus is needed on the optimal frequency of EMB