通过超声心动图改善对hDAF转基因猪心脏异种移植食蟹猴受体移植物功能的评估。
Improved assessment of graft function by echocardiography in cynomolgus monkey recipients of hDAF-transgenic pig cardiac xenografts.
作者信息
Stalder Mario, Tye Terry, Lam Tuan T, Chan Michael C Y, Berry Gerald J, Borie Dominic C, Morris Randall E
机构信息
Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
出版信息
J Heart Lung Transplant. 2005 Feb;24(2):215-21. doi: 10.1016/j.healun.2003.09.041.
BACKGROUND
The current practice of evaluating heterotopic heart xenografts by palpation allows only detection of severe graft dysfunction, which indicates terminal graft failure. Therefore, we evaluated whether echocardiography is a better method of detecting early graft dysfunction as a marker of rejection in abdominal pig heart xenografts in cynomolgus monkeys.
METHODS
Six cynomolgus monkeys received heterotopic heart transplants from pig donors transgenic for human decay-accelerating factor (hDAF). Induction therapy consisted of either cyclophosphamide or rabbit anti-thymocyte globulin. Maintenance therapy consisted of cyclosporine or tacrolimus, steroids, and sodium mycophenolate or mycophenolate mofetil, GAS914 (alphaGal oligosaccharide containing glycoconjugate), and for some animals TP10 (soluble complement receptor type 1). Echocardiography was performed immediately after transplantation and 3 times a week after surgery. We scored contractility and measured left ventricular wall thickness. Impaired contractility or increased wall thickness were considered graft dysfunction and were treated with pulse steroids. Palpation score was recorded daily. We also obtained myocardial biopsy specimens.
RESULTS
Palpation score remained at 4 out of 4 in all animals until 2 to 5 days before final graft failure, whereas echocardiography detected several episodes of impaired graft function, either decreased left ventricular contractility or increased left ventricular wall thickness before graft failure. Treatment with pulse steroids improved graft function only during early episodes of graft impairment. Final graft failure was steroid resistant and caused by severe vascular rejection.
CONCLUSIONS
Echocardiography is a better method of assessing graft dysfunction than is palpation. Therefore, echocardiography may detect early rejection episodes of heterotopic heart xenografts in non-human primates.
背景
目前通过触诊评估异位心脏异种移植的方法只能检测到严重的移植物功能障碍，这表明移植物已进入终末期衰竭。因此，我们评估了超声心动图是否是检测腹部猪心脏异种移植到食蟹猴体内早期移植物功能障碍（作为排斥反应标志物）的更好方法。
方法
六只食蟹猴接受了来自转人衰变加速因子（hDAF）基因猪供体的异位心脏移植。诱导治疗采用环磷酰胺或兔抗胸腺细胞球蛋白。维持治疗包括环孢素或他克莫司、类固醇、霉酚酸钠或霉酚酸酯、GAS914（含α-半乳糖寡糖的糖缀合物），部分动物还使用了TP10（可溶性1型补体受体）。移植后立即进行超声心动图检查，术后每周进行3次。我们对收缩性进行评分并测量左心室壁厚度。收缩性受损或壁厚度增加被视为移植物功能障碍，并采用脉冲类固醇进行治疗。每天记录触诊评分。我们还获取了心肌活检标本。
结果
在所有动物中，直到最终移植物衰竭前2至5天，触诊评分一直保持在4分（满分4分），而超声心动图在移植物衰竭前检测到几次移植物功能受损情况，即左心室收缩性降低或左心室壁厚度增加。脉冲类固醇治疗仅在移植物损伤的早期阶段改善了移植物功能。最终的移植物衰竭对类固醇耐药，是由严重的血管排斥反应引起的。
结论
超声心动图是一种比触诊更好的评估移植物功能障碍的方法。因此，超声心动图可能检测到非人灵长类动物异位心脏异种移植的早期排斥反应。
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