To manufacture tissue engineering-based functional tissues, scaffold materials that can be sufficiently vascularized to mimic the functionality and complexity of native tissues are needed. Currently, vascular network bioengineering is largely carried out using natural hydrogels as embedding scaffolds, but most natural hydrogels have poor mechanical stability and durability, factors that critically limit their widespread use. In this study, we examined the suitability of gelatin-phenolic hydroxyl (gelatin-Ph) hydrogels that can be enzymatically crosslinked, allowing tuning of the storage modulus and the proteolytic degradation rate, for use as injectable hydrogels to support the human progenitor cell-based formation of a stable and mature vascular network. Porcine gelatin-Ph hydrogels were found to be cytocompatible with human blood-derived endothelial colony-forming cells and white adipose tissue-derived mesenchymal stem cells, resulting in >87% viability, and cell proliferation and spreading could be modulated by using hydrogels with different proteolytic degradability and stiffness. In addition, gelatin was extracted from mouse dermis and murine gelatin-Ph hydrogels were prepared. Importantly, implantation of human cell-laden porcine or murine gelatin-Ph hydrogels into immunodeficient mice resulted in the rapid formation of functional anastomoses between the bioengineered human vascular network and the mouse vasculature. Furthermore, the degree of enzymatic crosslinking of the gelatin-Ph hydrogels could be used to modulate cell behavior and the extent of vascular network formation in vivo. Our report details a technique for the synthesis of gelatin-Ph hydrogels from allogeneic or xenogeneic dermal skin and suggests that these hydrogels can be used for biomedical applications that require the formation of microvascular networks, including the development of complex engineered tissues.

Plasma-containing products are given during the pre-anhepatic stage of liver transplant surgery to correct abnormal thromboelastogram (TEG) values and prevent blood loss due to coagulation defects. However, evidence suggests that abnormal TEG results do not always predict bleeding. We questioned what effect using higher TEG values to initiate treatment would have on blood loss. A single transfusion protocol was used for all patients who underwent liver transplantation between 2007 and 2010. Thirty-eight patients received coagulation products when standard TEG cutoff values were exceeded, whereas another 39 patients received coagulation products when the TEG values were 35% greater than normal. The results of postoperative coagulation tests for total blood loss and the use of blood products were compared for the 2 groups. When the critical TEG values for transfusion were higher, significantly fewer units of fresh frozen plasma (5.58 6 6.49 versus 11.53 6 6.66 U) and pheresis platelets (1.84 6 1.33 versus 3.55 6 1.43 U) were used. There were no differences in blood loss or postoperative blood product use. In conclusion, the use of higher critical TEG values to initiate the transfusion of plasma-containing products is not associated with increased blood loss. Further testing is necessary to identify what TEG value predicts bleeding due to a deficit in coagulation factors. Liver Transpl 18:1254-1258, 2012. V C 2012 AASLD.Received October 10, 2011; accepted June 13, 2012.Blood transfusions in liver transplant recipients are associated with an increased risk of infection and lung injury.1 This leads to increases in morbidity and mortality.2 Other outcome studies have shown that intraoperative transfusions of plasma products significantly reduce 1-year survival 3-5 and increase morbidity in liver transplant recipients. 6Physicians have used the thromboelastogram (TEG) as a tool for identifying abnormal coagulation. TEG can discriminate between different phases of the coagulation system and is, therefore, useful for identifying clotting abnormalities and guiding the administration of blood products.In 2007, we reported using less frozen plasma in transplant patients when transfusions were guided by standard TEG cutoff values instead of the international normalized ratio (INR)/prothrombin time and platelet counts. 7 We concluded that TEG was a

The outcomes of living donor liver transplant patients who had fluid therapy guided by an SVV less than 10% were similar to those of patients who were given fluids to reach a CVP of 10 mmHg. Our findings suggest that the two measures of vascular filling are similar in liver transplant recipients with demographic characteristics similar to those of our patients.

Many studies have shown that crosstalk exists between apoptosis and autophagy, despite differences in mechanisms between these processes. Paeonol, a major phenolic compound isolated from Moutan Cortex Radicis, the root bark of Paeonia × suffruticosa Andrews (Paeoniaceae), is widely used in traditional Chinese medicine as an antipyretic, analgesic and anti-inflammatory agent. In this study, we investigated the detailed molecular mechanisms of the crosstalk between apoptosis and autophagy underlying the cardioprotective effects of paeonol in rats subjected to myocardial ischemia/reperfusion (I/R) injury. Myocardial I/R injury was induced by occlusion of the left anterior descending coronary artery (LAD) for 1 h followed by 3 h of reperfusion. Paeonol was intravenously administered 15 min before LAD ligation. We found that paeonol significantly improved cardiac function after myocardial I/R injury and significantly decreased myocardial I/R-induced arrhythmia and mortality. Paeonol also significantly decreased myocardial infarction and plasma LDH activity and Troponin-I levels in carotid blood after I/R. Compared with vehicle treatment, paeonol significantly upregulated Bcl-2 protein expression and significantly downregulated the cleaved forms of caspase-8, caspase-9, caspase-3 and PARP protein expression in the I/R injured myocardium. Myocardial I/R-induced autophagy, including the increase of Beclin-1, p62, LC3-I, and LC3-II protein expression in the myocardium was significantly reversed by paeonol treatment. Paeonol also significantly increased the Bcl-2/Bax and Bcl-2/Beclin-1 ratios in the myocardium after I/R injury. The cardioprotective role of paeonol during I/R injury may be due to its mediation of crosstalk between apoptotic and autophagic signaling pathways, which inhibits apoptosis and autophagic cell death.

In adults, intraoperative administration of tramadol could result in earlier recovery and less sedation than morphine. In this controlled, randomized, double-blind study, we investigated whether an intraoperative initial dose of tramadol could cause more rapid awakening from general anesthesia, less sedation, and earlier tracheal extubation than morphine in children during the immediate postoperative period. Forty children aged 1-6 yr, scheduled for atrial or ventricular septal defect repair and tracheal extubation in the pediatric intensive care unit, were randomly allocated to receive morphine, initial dose 0.2 mg/kg, or tramadol 2 mg/kg given at the end of sternal closure, followed by nurse-controlled analgesia (bolus 0.02 mg/kg of morphine and 0.2 mg/kg of tramadol) with background infusions (0.015 mg x kg(-1) x h(-1) for morphine and 0.15 mg x kg(-1) x h(-1) for tramadol). Postoperatively, children receiving tramadol had earlier awakening from general anesthesia (P = 0.02) and were less sedated at 1 and 2 h postoperatively (P = 0.03 and P = 0.01, respectively). Tracheal extubation was earlier in the tramadol group (P = 0.01). Lengths of pediatric intensive care unit stay did not differ between groups. Times to first trigger of nurse-controlled analgesia bolus and objective pain scores during the 48 h observation period were comparable between groups. The incidence of desaturation and emesis were similar between groups. The patients ate well and did not differ on Day 1 or Day 2.