Pinto, BB;
Ritter, C;
Michels, M;
Gambarotta, N;
Ferrario, M;
Dal-Pizzol, F;
Singer, M;
(2017)
Characterization of brain-heart interactions in a rodent model of sepsis.
Molecular Neurobiology
, 54
(5)
pp. 3745-3752.
10.1007/s12035-016-9941-z.
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Abstract
Loss of heart rate variability (HRV) and autonomic dysfunction are associated with poor outcomes in critically ill patients. Neuronal networks comprising brainstem and hypothalamus are involved in the "flight-or-fight" response via control over the autonomic nervous system and circulation. We hypothesized that sepsis-induced inflammation in brain regions responsible for autonomic control is associated with sympathovagal imbalance and depressed contractility. Sepsis was induced by fecal slurry injection in fluid-resuscitated rats. Sham-operated animals served as controls. Echocardiography-derived peak velocity (PV) was used to separate septic animals into good (PV ≥0.93 m/s, low 72-h mortality) and bad (PV <0.93, high 72-h mortality) prognosis. Cytokine protein levels were assessed by ELISA. All experiments were performed at 24 h post-insult. Increased levels of inflammation and oxidative injury were observed in the hypothalamus (TNF-α, IL-10, nitrite and nitrate and carbonyl groups) and brainstem (IL-1, IL-6, IL-10, nitrite and nitrate and carbonyl groups) of the septic animals (p < 0.05 vs. sham), but not in the pre-frontal cortex, an area not directly implicated in control of the autonomic nervous system. Good prognosis septic animals had increased sympathetic output and increased left ventricular contractility (p < 0.05 vs. sham). There was a significant inverse correlation between high frequency power (a marker of parasympathetic outflow) and contractility (r = -0.73, p < 0.05). We found no correlation between the degree of inflammation or injury to autonomic centers and cardiovascular function. In conclusion, control of autonomic centers and cardiac function in our long-term rodent model of sepsis was related to clinical severity but not directly to the degree of inflammation.
| Type: | Article |
|---|---|
| Title: | Characterization of brain-heart interactions in a rodent model of sepsis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s12035-016-9941-z |
| Publisher version: | http://dx.doi.org/10.1007/s12035-016-9941-z |
| Language: | English |
| Additional information: | © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| Keywords: | Autonomic nervous system, Contractility, Encephalopathy, Heart rate variability, Inflammation, Sepsis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1508356 |
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