Afferent reinnervation after lung transplantation in the rat

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 pulmonary isografting (n = 52). Normal rats (n = 21) and rats undergoing left hilar stripping (n = 14) served as control subjects. Afferent reinnervation was tested physiologically by reflex bradycardia in response to intravenous infusion of capsaicin (30 microg/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 left lung or isograft. Whereas rats early after surgical denervation lost the reflex after right pulmonary artery occlusion, rats examined 8 months or longer after surgery showed potent reflex bradycardia in response to capsaicin, as did the control rats. Immunohistochemical staining for sensory neuron-specific substances, such as calcitonin gene-related peptide and substance P, were identified only in the right native lung and left pulmonary isografts 2 months or longer after transplantation. Fluorogold 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. These experiments provide physiological, 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 pulmonary isografting in the rat.