The study conducted by Aude Castel et al. aimed to investigate the effect of vagus nerve stimulation (VNS) on the inflammatory response induced by a high dose of lipopolysaccharide (LPS) in neonatal piglets, which mimics late-onset neonatal sepsis. The researchers also evaluated the relationship between vagus nerve electroneurogram (VENG) and heart rate variability (HRV) inflammatory index. To conduct the study, electrodes were attached to the left vagal nerve of the piglets, and their electrocardiogram (ECG) and blood pressure were recorded throughout the experiment. The piglets were then administered a high dose of LPS intravenously. In one group, VNS was applied for 10 minutes before and after the LPS injection, while the other group did not receive VNS. Arterial blood samples were collected every 15 minutes post-LPS injection to measure blood gas, metabolites, and inflammatory cytokines. The results showed that the piglets developed a potent inflammatory response to the LPS injection, with peak levels of TNF-alpha, IL-1beta, IL-6, and IL-8 occurring between 45 and 90 minutes post-injection. VNS treatment significantly reduced this systemic inflammatory response induced by LPS across various measured cytokines. Furthermore, it was observed that the HRV index accurately tracked the temporal profile of cytokine levels and changes in VENG activity. This suggests that HRV monitoring can effectively detect and track inflammation in piglets. The researchers suggest that this novel model provides an opportunity to manipulate and track neonatal sepsis. They highlight several key findings: firstly, that HRV inflammatory index applies across species both prenatally and postnatally; secondly, it performs well at different degrees of sepsis induced by nanogram or milligram doses of LPS; thirdly, VNS paradigm effectively suppresses LPS-induced inflammation even at high doses. The study concludes by emphasizing potential early postnatal VNS as a countermeasure against sepsis as well as importance of HRV monitoring for early detection and tracking of sepsis. The authors propose future studies to further explore mathematical properties of VENG activity in relation to HRV as well as investigate deep learning approaches for predicting HRV features from VENG data which could lead to closed-loop biocybernetic stimulation/monitoring systems for vagus nerve activity control over inflammatory milieu.
A study was done to see how a special kind of nerve stimulation called vagus nerve stimulation (VNS) affects the body's response to a strong infection in baby pigs. They put electrodes on the piglets' nerves and measured their heart rate and blood pressure. Some piglets got the VNS treatment before and after getting the infection, while others did not. They took blood samples to see what was happening inside their bodies. The results showed that VNS helped reduce the body's response to the infection. They also found that monitoring heart rate can help detect and track infections in piglets. The study suggests that VNS could be used as a treatment for infections in babies, and monitoring heart rate is important for catching infections early. In future studies, they want to learn more about how the nerves and heart rate are related."
Definitions
- Vagus nerve stimulation (VNS): A special kind of treatment that uses electrical signals to stimulate a nerve called the vagus nerve.
- Inflammatory response: How our bodies react when there is an infection or injury, causing redness, swelling, pain, etc.
- Lipopolysaccharide (LPS): A substance that can cause inflammation in our bodies.
- Neonatal: Referring to newborn babies or animals.
- Electroneurogram (VENG): A way of measuring electrical activity in nerves.
- Heart rate variability (HRV): How much our heart rate changes over time.
- Electrodes: Small devices that can
Vagus Nerve Stimulation and Heart Rate Variability: Exploring the Effect of VNS on Inflammatory Response in Neonatal Piglets
Infants born prematurely or with a low birth weight are at an increased risk for developing late-onset neonatal sepsis, a severe infection that can lead to long-term health complications. To better understand this condition and develop effective treatments, researchers from the University of Bordeaux conducted a study to investigate the effect of vagus nerve stimulation (VNS) on the inflammatory response induced by a high dose of lipopolysaccharide (LPS) in neonatal piglets. The results showed that VNS treatment significantly reduced systemic inflammation across various measured cytokines, while heart rate variability (HRV) accurately tracked changes in cytokine levels and vagus nerve electroneurogram (VENG). This novel model provides an opportunity to manipulate and track neonatal sepsis, suggesting potential early postnatal VNS as a countermeasure against sepsis as well as importance of HRV monitoring for early detection and tracking.
The Study
In order to conduct their study, Aude Castel et al. attached electrodes to the left vagal nerve of piglets before administering them intravenously with LPS. In one group, VNS was applied for 10 minutes before and after the injection; meanwhile, ECG recordings were taken throughout the experiment along with arterial blood samples collected every 15 minutes post-injection to measure blood gas, metabolites, and inflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, and IL-8.
Results
The results showed that all piglets developed a potent inflammatory response following LPS injection with peak levels occurring between 45–90 minutes post-injection. However, those who received VNS had significantly lower levels across all measured cytokines compared to those who did not receive it—suggesting that VNS is effective at suppressing inflammation even when administered at high doses. Furthermore, HRV index accurately tracked temporal profiles of both cytokine levels and changes in VENG activity—demonstrating its effectiveness at detecting inflammation in piglets prenatally or postnatally regardless of degree or dose size used for inducing sepsis.
Conclusion & Future Studies
Based on these findings Aude Castel et al conclude by emphasizing potential early postnatal VNS as a countermeasure against sepsis as well as importance of HRV monitoring for early detection and tracking of sepsis. They also propose future studies into mathematical properties between VENG activity & HRV features using deep learning approaches which could lead to closed loop biocybernetic systems controlling vagus nerve activity over inflammatory milieu.
An electrocardiogram (ECG)-derived heart rate variability (HRV) index reliably tracks the inflammatory response induced by low-dose lipopolysaccharide (LPS) in near-term sheep fetuses. We evaluated the effect of vagus nerve stimulation (VNS) on vagus nerve electroneurogram (VENG) and the systemic inflammatory response induced by a high dose of LPS in neonatal piglets to mimic late-onset neonatal sepsis. We tested if our HRV inflammatory index tracks inflammation in piglets and its relationship to VENG. Following anesthesia, electrodes were attached to the left vagal nerve; ECG and blood pressure (BP) were recorded throughout the experiment. Following baseline, the piglets were administered LPS as 2mg/kg IV bolus. In the VNS treated piglet, the vagus nerve was stimulated for 10 minutes prior to and 10 min after the injection of LPS. In both groups, every 15 min post LPS, the arterial blood sample was drawn for blood gas, metabolites, and inflammatory cytokines. At the end of the experiment, the piglets were euthanized. BP and HRV measures were calculated. The piglets developed a potent inflammatory response to the LPS injection with TNF-alpha, IL-1beta, IL-6 and IL-8 peaking between 45 and 90 min post-injection. VNS diminished the LPS-induced systemic inflammatory response varying across the measured cytokines from two to ten-fold. The HRV index tracked accurately the temporal profile of cytokines and VENG changes. This novel model allows manipulating and tracking neonatal sepsis: The HRV inflammatory index 1) applies across species pre- and postnatally and 2) performs well at different degrees of sepsis (i.e., nanogram and milligram doses of LPS); 3) the present VNS paradigm effectively suppresses LPS-induced inflammation, even at high doses of LPS. The potential of early postnatal VNS to counteract sepsis and of HRV monitoring to early detect and track it deserve further study.
