Experimental Study On Changes Of Subcutaneous Sympathetic Nerve Discharges And Cervical Vagal Stimulation In Acute Pulmonary Embolism

Objective: Activation of the sympathetic nervous system may be involved in the development of acute pulmonary embolism(APE). In this study, we explored the changes of sympathetic nervous system(SNS) activity by directly recording sympathetic nerve activity in APE.Methods: Eleven healthy adult mongrel dogs were anesthetized by intraperitoneal injection of 3% pentobarbital(30 mg/kg) and were in the supine position. Under an opening surgery, taking off the second rib, and a bipolar golden hooked-electrode was placed nearby on the postganglionic inferior cardiac sympathetic nerve(ICSN) to directly record discharges under direct visual, then, an APE model was established by injecting autologous blood clots, and recording ICSN discharges simultaneously. The gross and histological evaluations were performed on all retrieved samples after animals died.Results: Postganglionic ICSN discharges were recorded in all eleven dogs, and the process of changes of ICSN discharges were successfully recorded in eight dogs in APE. After APE, ICSN discharges frequency and amplitude increased significantly. After the analysis using relevant software, the average ICSN discharge frequency and amplitude were 168.45±23.81 Hz and 1.81±0.34μV separately at the baseline in eleven dogs, after excluding three dogs, were 178.13±17.25 Hz and 1.96±0.29μV separately, increasing to 274.25±31.48 Hz and 3.53±0.76μV separately after APE, the differences were statistically significant(all p<0.001). Gross examination showed pulmonary infarction, histological examination showed pulmonary embolism, alveolar wall necrosis and alveolar hemorrhage.Conclusion: The activation of the SNS was confirmed by directly recording the ICSN activity in APE, and it could provide experimental basis for the treatment of pulmonary embolism with the intervention of the autonomic nervous system.Objectives: Previous studies have brought about some promising results by inhibiting sympathetic nerve system in the treatment of acute pulmonary embolism(APE), and the activation of sympathetic nervous system in APE was confirmed by directly recording the sympathetic nerve activity in the first part of our experiments. Vagus nerve stimulation(VNS) may suppress sympathetic activation in APE. The aim of this study was to evaluate the short-term efficacy of cervical VNS on pulmonary hemodynamics of APE with a sham control in a canine model.Methods: Eighteen experimental canines were divided randomly to VNS group(n=10) and sham group(n=8). The Swan-Ganz catheter was implanted through the right jugular vein in all dogs, and the mean pulmonary arterial pressure(m PAP), pulmonary artery systolic blood pressure(PASP), pulmonary artery diastolic pressure(PADP) and pulmonary capillary wedge pressure(PCWP) were monitored in real time. Left cervical VNS was performed in VNS-Group, stimulation current was 1.0m A-5.0m A, pulse width was 1ms, pulse interval was 50 ms, and stimulation time was 15s/60 s, the whole stimulation duration was three hours. Similar procedures without electrical stimulation were conducted in the sham group. The animals were sacrificed, and the gross and histological evaluations were performed on all retrieved samples.Results: All of the animals survived the treatment. The experimental dogs were well tolerated to cervical VNS, and no obvious adverse reactions were observed. After pulmonary embolism, the m PAP increased from baseline 15.89±2.81 mm Hg to 46.21±4.27 mm Hg in VNS-Group dogs, and from 16.82±2.72 mm Hg to 47.88±4.50 mm Hg in sham-Group dogs, there was no statistical difference between the two groups(p=0.52). After 3h intervention, compared with sham-Group, the declines of m PAP、PASP and PADP in the VNS-Group were more obvious(-17.56/-13.56 mm Hg, p=0.07、-24.11/-20.07 mm Hg, p=0.13、-14.14/-12.10 mm Hg, p=0.15), but it did not reach statistical difference. Gross examination showed pulmonary infarction, histological examination showed pulmonary embolism, alveolar wall necrosis and alveolar hemorrhage.Conclusions: Compared with the sham-Group, short-term cervical VNS could decrease the pulmonary circulation pressure in canine model of APE, but did not reach statistical significance. However, due to the limitations of short observation time and less evaluation index, it could not make a definite decision on the treatment of pulmonary embolism with cervical VNS, which needed to design more in-depth and comprehensive experimental studies to evaluate the efficacy.