Heart rate elevations during early sepsis predict death in fluid-resuscitated rats with fecal peritonitis

Rudiger, Alain; Jeger, Victor; Arrigo, Mattia; Schaer, Christian A.; Hildenbrand, Florian F.; Arras, Margarete; Seifert, Burkhardt; Singer, Mervyn; Schoedon, Gabriele; Spahn, Donat R.; Béttex, Dominique

doi:10.1186/s40635-018-0190-5

Cited by 11 publications

(8 citation statements)

References 42 publications

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“…The animals appeared to have different degrees of pathologic reaction, although all animals were treated with the same protocol. This variation in clinical parameters was also observed in previous studies 36 – 39 using the same sepsis induction protocol. A follow-up investigation with larger number of animals could improve the precision of the sample mean of the BFI.…”

Section: Discussionsupporting

confidence: 86%

Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

Park

Lee

et al. 2021

Sci Rep

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We developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.

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Section: Discussionsupporting

confidence: 86%

Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

Park

Lee

et al. 2021

Sci Rep

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“…Alterations proved to be most pronounced in the early post‐insult phase suggesting a disturbed resting phase with elevated activity levels and heart rate. Heart rate elevations have been discussed previously as a marker of distress in laboratory rodents exposed to surgical intervention, tumor models, or a sepsis model …”

Section: Discussionmentioning

confidence: 99%

“…Heart rate elevations have been discussed previously as a marker of distress in laboratory rodents exposed to surgical intervention, tumor models, or a sepsis model. 9,[33][34][35][36] In this context, it is of interest that heart rate variability has been reported to be differentially affected by chronic stress exposure with a decrease in time-domain indices and an increase in frequency domain indices. 37 The lack of any relevant and robust alterations in the electrical post-SE model may thus argue against a high level of stress.…”

Section: Discussionmentioning

confidence: 99%

Toward evidence‐based severity assessment in rat models with repeated seizures: III. Electrical post‐status epilepticus model

et al. 2019

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Objective Ethical approval of experiments in chronic epilepsy models requires a careful balancing of the expected gain‐in‐knowledge with the level of distress. Thus recommendations for evidence‐based severity assessment and classification are urgently needed for preclinical epilepsy research. Methods Therefore, we have completed a comprehensive analysis of alterations in behavioral, biochemical, and physiological parameters in a rat electrical post‐status epilepticus model. Selected parameters were repeatedly analyzed during different experimental phases to obtain information about the level of distress throughout the course of the model. Results Behavioral patterns comprised an increase in activity along with a reduction in risk assessment behavior, active social interaction, saccharin preference as well as nonessential, but evolutionary‐determined behavior such as nest building and burrowing. Among the biochemical parameters, fecal corticosterone metabolites proved to be increased in different phases of the experiment. In the early post‐insult phase, this increase was reflected by elevated serum corticosterone concentrations. Telemetric recordings demonstrated increases in home cage activity and heart rate in selected experimental phases but argued against relevant changes in heart rate variability. Comparison between animals with tethered or telemetric recordings including a principal component analysis revealed differences between both groups. Significance The present findings further confirm that burrowing behavior and saccharin preference might serve as valid parameters for severity assessment in chronic epilepsy models. Considering the course of alterations providing evidence for a more pronounced level of distress in the early phase following status epilepticus (SE), we suggest a classification of the electrical post‐SE model as severe. This suggestion may serve as a guidance for laboratory‐specific evaluations. Comparison between data from animals with tethered and telemetric recordings indicated an impact of the mode of recordings. However, further research is necessary to analyze the validity of telemetry as a putative refinement measure.

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“…[137]). Peripheral and central inflammation in animals indeed increases the activity of the sympathetic nervous system [138,139,140].…”

Section: Inflammation As a Risk Factor For Depression And Suicidementioning

confidence: 99%

Novel Treatment Targets Based on Insights in the Etiology of Depression: Role of IL-6 Trans-Signaling and Stress-Induced Elevation of Glutamate and ATP

Kalkman¹

2019

Pharmaceuticals

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Inflammation and psychological stress are risk factors for major depression and suicide. Both increase central glutamate levels and activate the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Both factors also affect the function of the chloride transporters, Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2), and provoke interleukin-6 (IL-6) trans-signaling. This leads to measurable increases in circulating corticosteroids, catecholamines, anxiety, somatic and psychological symptoms, and a decline in cognitive functions. Recognition of the sequence of pathological events allows the prediction of novel targets for therapeutic intervention. Amongst others, these include blockade of the big-K potassium channel, blockade of the P2X4 channel, TYK2-kinase inhibition, noradrenaline α2B-receptor antagonism, nicotinic α7-receptor stimulation, and the Sgp130Fc antibody. A better understanding of downstream processes evoked by inflammation and stress also allows suggestions for tentatively better biomarkers (e.g., SERPINA3N, MARCKS, or 13C-tryptophan metabolism).

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Heart rate elevations during early sepsis predict death in fluid-resuscitated rats with fecal peritonitis

Cited by 11 publications

References 42 publications

Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography

Toward evidence‐based severity assessment in rat models with repeated seizures: III. Electrical post‐status epilepticus model

Novel Treatment Targets Based on Insights in the Etiology of Depression: Role of IL-6 Trans-Signaling and Stress-Induced Elevation of Glutamate and ATP

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