Peiris Rachel M, May Clive N, Booth Lindsea C, McAllen Robin M, McKinley Michael J, Hood Sally, Martelli Davide, Bellomo Rinaldo, Lankadeva Yugeesh R
Preclinical Critical Care Unit, Florey Institute of Neuroscience and Mental Health, University of Melbourne, 30 Royal Parade Parkville, Victoria, 3052, Australia.
Department of Critical Care, Melbourne Medical School, University of Melbourne, Victoria, Australia.
Intensive Care Med Exp. 2023 Aug 3;11(1):53. doi: 10.1186/s40635-023-00530-6.
The autonomic nervous system can modulate the innate immune responses to bacterial infections via the splanchnic sympathetic nerves. Here, we aimed to determine the effects of bilateral splanchnic sympathetic nerve denervation on blood pressure, plasma cytokines, blood bacterial counts and the clinical state in sheep with established bacteremia.
Conscious Merino ewes received an intravenous infusion of Escherichia coli for 30 h (1 × 10 colony forming units/mL/h) to induce bacteremia. At 24 h, sheep were randomized to have bilaterally surgically implanted snares pulled to induce splanchnic denervation (N = 10), or not pulled (sham; N = 9).
Splanchnic denervation did not affect mean arterial pressure (84 ± 3 vs. 84 ± 4 mmHg, mean ± SEM; P = 0.7) compared with sham treatment at 30-h of bacteremia. Splanchnic denervation increased the plasma levels of the pro-inflammatory cytokine interleukin-6 (9.2 ± 2.5 vs. 3.8 ± 0.3 ng/mL, P = 0.031) at 25-h and reduced blood bacterial counts (2.31 ± 0.45 vs. 3.45 ± 0.11 log10 [CFU/mL + 1], P = 0.027) at 26-h compared with sham treatment. Plasma interleukin-6 and blood bacterial counts returned to sham levels by 30-h. There were no differences in the number of bacteria present within the liver (P = 0.3). However, there was a sustained improvement in clinical status, characterized by reduced respiratory rate (P = 0.024) and increased cumulative water consumption (P = 0.008) in splanchnic denervation compared with sham treatment.
In experimental Gram-negative bacteremia, interrupting splanchnic sympathetic nerve activity increased plasma interleukin-6, accelerated bacterial clearance, and improved clinical state without inducing hypotension. These findings suggest that splanchnic neural manipulation is a potential target for pharmacological or non-pharmacological interventions.
自主神经系统可通过内脏交感神经调节对细菌感染的固有免疫反应。在此，我们旨在确定双侧内脏交感神经去神经支配对已发生菌血症绵羊的血压、血浆细胞因子、血液细菌计数及临床状态的影响。
清醒的美利奴母羊静脉输注大肠杆菌30小时（1×10菌落形成单位/毫升/小时）以诱导菌血症。在24小时时，将绵羊随机分为两组，一组通过手术牵拉双侧植入的圈套器以诱导内脏去神经支配（n = 10），另一组不牵拉（假手术组；n = 9）。
与菌血症30小时时的假手术组相比，内脏去神经支配对平均动脉压无影响（84±3 vs. 84±4 mmHg，均值±标准误；P = 0.7）。与假手术组相比，内脏去神经支配在25小时时增加了促炎细胞因子白细胞介素-6的血浆水平（9.2±2.5 vs. 3.8±0.3 ng/mL，P = 0.031），并在26小时时降低了血液细菌计数（2.31±0.45 vs. 3.45±0.11 log10[CFU/mL + 1]，P = 0.027）。血浆白细胞介素-6和血液细菌计数在30小时时恢复到假手术组水平。肝脏内细菌数量无差异（P = 0.3）。然而，与假手术组相比，内脏去神经支配组的临床状态持续改善，表现为呼吸频率降低（P = 0.024）和累计饮水量增加（P = 0.008）。
在实验性革兰氏阴性菌血症中，中断内脏交感神经活动可增加血浆白细胞介素-6、加速细菌清除并改善临床状态，而不引起低血压。这些发现表明，内脏神经调控是药物或非药物干预的潜在靶点。
