Author Correction: Consistent success in life-supporting porcine cardiac xenotransplantation.

In this Letter, Mayuko Kurome and Valeri Zakhartchenko have been added to the author list (affiliated with Institute of Molecular Animal Breeding and Biotechnology, Gene Center, LMU Munich, Munich, Germany). The author list and 'Author contributions' section have been corrected online; see accompanying Amendment.

Consistent success in life-supporting porcine cardiac xenotransplantation.

Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.

Effects of 20-minute warm ischemia on coronary endothelial function of pig donor hearts after cardiac death / 中国组织工程研究

BACKGROUND:Myocardial and coronary endothelial injury occurs in donor hearts due to warm ischemia during cardiac transplantation. Coronary endothelial structure and function play a critical role in long-term outcomes for patients after cardiac transplantation. OBJECTIVE:To study the effect of hypoxia-induced warm ischemia (20 minutes) on coronary endothelial function of porcine donor hearts after cardiac death (DCD). METHODS:Sixteen healthy Swedish domestic pigs were randomized into control (n=6), DCD (n=5), and DCD plus cold storage (n=5) groups, respectively. A DCD model in pigs was established using the method of hypoxia-induced 20-minute warm ischemia in the DCD and DCD plus cold storage groups. Isolation of the heart left anterior descending coronary artery or combined with heart preservation pretreatment for 4 hours was performed in the DCD and DCD plus cold storage groups. The maximum coronary endothelium-dependent relaxation was determined in the three groups. RESULTS AND CONCLUSION:There were no significant differences in the maximum coronary endothelium-dependent relaxation and the minus logarithmic of substance concentration induced 50%maximal relaxation among three groups (P>0.05). These results indicate that 20-minute warm ischemia cannot lead to obvious coronary endothelial dysfunction. In addition, DCD combined with 4-hour cold storage does not affect coronary endothelial function.

A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction. Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model. The purpose of this study was to establish a novel, minimally invasive rat model of normothermic CPB model without blood priming.</p><p><b>METHODS</b>Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n = 10) and control group (n = 10). All rats were anaesthetized and mechanically ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery. The volume of the priming solution, composed of 6% HES 130/0.4 and 125 IU heparin, was less than 12 ml. The surface of the hollow fiber oxygenator was 0.075 m(2). CPB was conducted for 60 minutes at a flow rat of 100-120 ml × kg (-1)× min(-1) in CPB group. Oxygen flow/perfusion flow was 0.8 to 1.0, and the mean arterial pressure remained 60-80 mmHg.</p><p><b>RESULTS</b>All CPB processes were successfully achieved. Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges. The vital signs of all rats were stable.</p><p><b>CONCLUSIONS</b>The establishment of CPB without blood priming in rats can be achieved successfully. The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions. This novel, recovery, and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.</p>

Detection of bronchial function of NHBD lung following one-h warm ischemia by organ bath model / 华中科技大学学报（医学）（英德文版）

This study investigated the feasibility and effects of organ bath to be used for detection of bronchial function of non-heart-beating donor (NHBD) lung after 1-h warm ischemia. Sixteen Swedish pigs were divided into two groups randomly: heart-beating donor (HBD) group and NHBD with 1-h warm ischemia (NHBD-1 h) group. The bronchial rings whose lengths and inner diameters were both 1.5 mm were obtained from isolated left lungs of all the pigs. Acetylcholine, arachidonic acid natrium and papaverine were used to test and compare the contractile and relaxant function of bronchial smooth muscles and epithelium-dependent relaxation (EpiDR) response between HBD and NHBD-1 h groups. The results showed that there was no significant difference in the values of bronchial precontraction between HBD and NHBD-1 h groups (5.18+/-0.07 vs 5.10+/-0.11 mN, P>0.05). No significant difference in the values of EpiDR responses between HBD and NHBD-1 h groups (1.26+/-0.05 vs 1.23+/-0.07 mN, P>0.05) was observed either. During the process of EpiDR induction, the rings had no spontaneous relaxation in two groups. In addition, papaverine solution completely relaxed the bronchial smooth muscles of all bronchial rings. It was concluded that after warm ischemia for 1 h, the contractile and relaxant abilities of bronchial smooth muscles, and the epithelium-dependent adjustment both kept intact. Organ bath model could be a liable and scientific way to evaluate the bronchial function of NHBD lung.

Effects of perfusion pressure with cold cardioplegic solution on porcine coronary arterial endothelial and smooth muscle function / 第三军医大学学报

Objective To investigate the effects of perfusion pressure with a cardioplegic solution on endothelium-dependent relaxation and smooth muscle function of porcine coronary artery. Methods The hearts were infused with a modified St.Thomas’ hospital solution at the pressures of 40, 60 and 80 mmHg. The distal part of porcine left anterior descending coronary artery (LAD) having a diameter of 1.0-1.5 mm, was dissected free from the surrounding tissue, cut into 1 mm long segments, immediately transferred to organ baths for the evaluation of endothelial and smooth muscle function. Results Smooth muscle function was not affected after cardioplegic flushing at the pressures used in this study. The maximal endothelium-dependent relaxations of the vessels in 40 and 60 mmHg groups were not reduced compared to fresh segments . The maximal EDR was significantly reduced to (90.8?2.2)% (P