Neonatal Sepsis Alters the Excitability of Regular Spiking Cells in the Nucleus of the Solitary Tract in Rats.

OBJECTIVE: Sepsis is a leading cause of mortality and morbidity in infants. Although the measures of autonomic dysfunction (e.g., reduced heart rate variability) predict mortality in sepsis, the mechanism of sepsis-induced autonomic dysfunction has remained elusive. The nucleus of the solitary tract (NTS) is a vital structure for the integrated autonomic response to physiological challenges. In the present study we hypothesized that sepsis alters the excitability of NTS neurons in a rat model of neonatal sepsis (14-day-old rats). METHODS AND RESULTS: Sepsis was induced by intraperitoneal injection of cecal slurry (CS) in rat neonates. The presence of autonomic dysfunction was confirmed by observing a significant reduction in both short-term and long-term heart rate variably following CS injection. We investigated the effect of polymicrobial sepsis on the electrophysiological properties of the medial NTS neurons using a whole cell patch clamp recording. Our results showed that the resting membrane potential in regular spiking neurons was significantly less polarized in the septic group (-37.6 ±â€Š1.76 mv) when compared with the control group (-54.7 ±â€Š1.73 mv, P < 0.001). The number of spontaneous action potentials in the septic group was also significantly higher than the control group (P < 0.05). In addition, the frequency and amplitude of the spontaneous excitatory post synaptic potentials was significantly higher in neurons recorded in the septic group (P < 0.001). Interestingly, regular spiking cells in the CS group exhibited a rebound action potential following hyperpolarization. Injection of depolarizing currents was associated with lower first spike latency and changes in rise slope of action potential (P < 0.001). CONCLUSIONS: We showed that polymicrobial sepsis increases the excitability of regular spiking cells in the medial NTS. These alterations can potentially affect neural coding and thus may contribute to an abnormal homeostatic or allostatic physiological response to sepsis and systemic inflammation.

Corrigendum: The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities.

[This corrects the article DOI: 10.3389/fphys.2019.00116.].

The Application of the Extended Poincaré Plot in the Analysis of Physiological Variabilities.

The Poincaré plot is a geometrical technique used to visualize and quantify the correlation between two consecutive data points in a time-series. Since the dynamics of fluctuations in physiological rhythms exhibit long-term correlation and memory, this study aimed to extend the Poincaré plot by calculating the correlation between sequential data points in a time-series, rather than between two consecutive points. By incorporating this so-called lag, we hope to integrate a temporal aspect into quantifying the correlation, to depict whether a physiological system holds prolonged association between events separated by time. In doing so, it attempts to instantaneously characterize the intrinsic behavior of a complex system. We tested this hypothesis on three different physiological time-series: heart rate variability in patients with liver cirrhosis, respiratory rhythm in asthma and body temperature fluctuation in patients with cirrhosis, to evaluate the potential application of the extended Poincaré method in clinical practice. When studying the cardiac inter-beat intervals, the extended Poincaré plot revealed a stronger autocorrelation for patients with decompensated liver cirrhosis compared to less severe cases using Pearson's correlation coefficient. In addition, long-term variability (known as SD2 in the extended Poincaré plot) appeared as an independent prognostic variable. This holds significance by acting as a non-invasive tool to evaluate patients with chronic liver disease and potentially facilitate transplant selection as an adjuvant to traditional criteria. For asthmatics, employing the extended Poincaré plot allowed for a non-invasive tool to differentially diagnose various classifications of respiratory disease. In the respiratory inter-breath interval analysis, the receiver operating characteristic (ROC) curve provided evidence that the extension of the Poincaré plot holds a greater advantage in the classification of asthmatic patients, over the traditional Poincaré plot. Lastly, the analysis of body temperature from patients using the extended Poincaré plot helped identify inpatients from outpatients with cirrhosis. Through these analyses, the extended Poincaré plot provided unique and additional information which could potentially make a difference in clinical practice. Conclusively, the potential use of our work lies in its possible application of predicting mortality for the organ allocation procedure in patients with cirrhosis and non-invasively distinguish between atopic and non-atopic asthma.

The effect of fractal-like mechanical ventilation on vital signs in a rat model of acute-on-chronic liver failure.

OBJECTIVE: The network of interactions between different organs is impaired in liver cirrhosis. Liver cirrhosis is associated with multi-system involvement, which eventually leads to multiple organ failure. This process is accelerated by a precipitating factor such as bacterial infection, which leads to respiratory distress, circulatory shock, neural dysfunction and very high mortality. Cirrhotic patients often have blunted respiratory sinus arrhythmia and impaired cardio-respiratory variability. Fractal-like mechanical ventilation is reported to enhance respiratory sinus arrhythmia and attenuate respiratory distress in experimental models. In the present study we hypothesise that fractal-like mechanical ventilation may improve the outcome of cirrhotic rats with multiple organ failure. APPROACH: Cirrhosis was induced by chronic biliary obstruction in rats. Acute multiple organ failure was induced by intraperitoneal injection of bacterial endotoxin in cirrhotic rats. The effect of conventional mechanical ventilation (with constant tidal volume and respiratory rate) or fractal-like ventilation (with the same average but variable tidal volume and respiratory rate) were assessed on vital signs, oxygen saturation and plasma alanine aminotransferase in anaesthetised cirrhotic rats. MAIN RESULTS: We demonstrated that fractal-like mechanical ventilation was accompanied by improved oxygen saturation, reduced heart rate and decreased liver injury following injection of bacterial endotoxin. Moreover, variable mechanical ventilation in cirrhotic rats reduced mortality and prevented a fall in short-term heart rate variability following endotoxin challenge in comparison with rats with constant mechanical ventilation. SIGNIFICANCE: We suggest further investigations into the beneficial effects of fractal-like ventilation strategy in critically ill patients with liver failure requiring organ support and mechanical ventilation.

The effect of endotoxin on heart rate dynamics in diabetic rats.

The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats.

Quantifying memory in complex physiological time-series.

In a time-series, memory is a statistical feature that lasts for a period of time and distinguishes the time-series from a random, or memory-less, process. In the present study, the concept of "memory length" was used to define the time period, or scale over which rare events within a physiological time-series do not appear randomly. The method is based on inverse statistical analysis and provides empiric evidence that rare fluctuations in cardio-respiratory time-series are 'forgotten' quickly in healthy subjects while the memory for such events is significantly prolonged in pathological conditions such as asthma (respiratory time-series) and liver cirrhosis (heart-beat time-series). The memory length was significantly higher in patients with uncontrolled asthma compared to healthy volunteers. Likewise, it was significantly higher in patients with decompensated cirrhosis compared to those with compensated cirrhosis and healthy volunteers. We also observed that the cardio-respiratory system has simple low order dynamics and short memory around its average, and high order dynamics around rare fluctuations.