Afferent Reinnervation After Lung Transplantation in the Rat

肺移植时去神经支配导致咳嗽反射丧失和局部防御机制减弱，是肺移植后感染发生率和严重程度增加的原因。我们研究了大鼠原位左肺同种异体移植后不同时间段是否存在自发传入神经再支配（n=52）。正常大鼠（n=21）和左肺门剥脱大鼠（n=14）作为对照。通过静脉注射辣椒素（30 μ g/kg）（一种辣椒提取物，刺激肺C-纤维）引起的反射性心动过缓，对传入神经再支配进行生理学测试。在右肺动脉阻塞之前和之后重复注射辣椒素以将所有肺血流转移到左肺或同种移植物。而大鼠手术后早期失去了右肺动脉闭塞后的反射，大鼠手术后8个月或更长时间表现出强有力的反射性心动过缓，辣椒素反应正常大鼠。感觉神经元特异性物质，如降钙素基因相关肽（CGRP）和P物质的免疫组织化学染色，仅在右自体肺和左肺移植后2个月或更长时间。荧光金只发现在同侧结状神经节后，左肺胸膜内注射神经元特异性示踪剂在大鼠去神经后8个月或less.The目前的实验提供的生理，形态学和神经学证据表明，传入肺神经支配，取消移植后早期，自发重建和功能的同侧迷走神经在大鼠肺同种异体移植后8个月。

Denervation at lung transplantation results in loss of cough reflex and attenuated local defense mechanisms, accounting for increased incidence and severity of infection after lung transplantation. We studied the presence or absence of spontaneous afferent reinnervation in rats at various intervals after orthotopic left lung isografting (n=52). Normal rats (n=21) and rats undergoing left hilar stripping (n=14) served as controls. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30mug/kg), an extract of paprika stimulating pulmonary C-fibers. Injection of capsaicin was repeated before and after right pulmonary artery occlusion to divert all pulmonary blood flow to the leftlung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin as did the normal rats. Immunohistochemical staining for sensory neuron specific substances, such as Calcitonin Gene-Related Peptide (CGRP) and substance P,were identified only in the right native lungs and left lung isografts 2 months or longer after transplantation. Fluoro-gold was found only in the ipsilateral nodose ganglion after left lung intrapleural injection of the neuron specific tracer in rats 8 months or longer after denervation.The current experiments provide physiologic, morphologic and neurologic evidence suggesting that afferent lung innervation, abolished early after transplantation, is spontaneously reestablished and functioning in the ipsilateral vagus nerve by 8 months after lung isografting in the rat.