Brandl U, Erhardt M, Jöckle H, Michel S, Thein E, Bittmann I, Brenner P, Burdorf L, Hammer C, Schmoeckel M, Reichart B
Department of Cardiac Surgery, Institute for Surgical Research, and Institute for Pathology, Ludwig Maximilians University of Munich, Munich, Germany.
Transplant Proc. 2006 Apr;38(3):733-4. doi: 10.1016/j.transproceed.2006.01.062.
Classic features of hyperacute rejection show differential severity in the inner compared to the outer myocardium. In the present study, regional blood flow (RBF) measured by fluorescent microspheres served as a marker of the extent of hyperacute rejection. Using a working heart model, hearts of nontransgenic and hDAF transgenic pigs were perfused with human blood. Additionally, hDAF transgenic pig hearts were perfused with human blood containing GAS914 or the GPIIb/IIIa inhibitor tirofiban. Injections of fluorescent microspheres into the donor heart were performed in situ and during perfusion. Reference arterial blood samples were collected from the inferior aorta and the afterload line. Perfusion was terminated before hyperacutely rejected hearts failed to pump against the afterload column. RBF was determined in tissue samples of standardized areas of the left atrium and ventricle. Each specimen was divided into subepicardial and subendocardial tissue samples. Fluorescence intensity was measured using an automated luminescence spectrometer. At the end of perfusion with human blood, hyperacutely rejected nontransgenic pig hearts showed a higher RBF in the subendocardium. In hDAF-transgenic pig hearts perfused with unmodified human blood the subendocardial/subepicardial blood flow ratio changed in favor of the subepicardium. This ratio was not further improved by GAS914. In contrast, tirofiban was able to assimilate subepicardial and subendocardial blood flow. In conclusion, RBF of hyperacutely rejected pig hearts was inhomogeneous. Inhibition of complement activation improved the reduced subepicardial RBF, but depletion of antibodies had no positive effect. The ability of tirofiban to further increase subepicardial RBF affirms thrombosis of subepicardial veins as the defining characteristic of hyperacute rejection.
超急性排斥反应的典型特征在心肌内层与外层表现出不同程度的严重性。在本研究中，通过荧光微球测量的局部血流量（RBF）作为超急性排斥反应程度的标志物。使用工作心脏模型，用人类血液灌注非转基因猪和hDAF转基因猪的心脏。此外，用含有GAS914或糖蛋白IIb/IIIa抑制剂替罗非班的人类血液灌注hDAF转基因猪心脏。在原位和灌注过程中向供体心脏注射荧光微球。从降主动脉和后负荷管线上采集参考动脉血样本。在超急性排斥反应的心脏无法对抗后负荷柱泵血之前终止灌注。在左心房和心室标准化区域的组织样本中测定RBF。每个标本分为心外膜下和心内膜下组织样本。使用自动发光光谱仪测量荧光强度。在用人类血液灌注结束时，超急性排斥反应的非转基因猪心脏的心内膜下RBF较高。在用未修饰的人类血液灌注的hDAF转基因猪心脏中，心内膜下/心外膜下血流比值向有利于心外膜的方向变化。GAS914并未进一步改善该比值。相比之下，替罗非班能够使心外膜下和心内膜下血流同化。总之，超急性排斥反应的猪心脏的RBF是不均匀的。补体激活的抑制改善了降低的心外膜下RBF，但抗体的消耗没有积极作用。替罗非班进一步增加心外膜下RBF的能力证实心外膜下静脉血栓形成是超急性排斥反应的决定性特征。
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