title: Characterization of Brain-Heart Interactions in a Rodent Model of Sepsis.
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.
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. Bernardo.bollenpinto@hcuge.ch.|Department of Anaesthesia, Emergency, and Intensive Care, Centro Hospitalar do Porto, Largo Prof. Abel Salazar, 4099-001, Porto, Portugal. Bernardo.bollenpinto@hcuge.ch.|Department of Anaesthesia, Pharmacology and Intensive Care, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil 4, 1205, Geneva, Switzerland. Bernardo.bollenpinto@hcuge.ch.
authors.forename: Bernardo Bollen
authors.initials: BB
authors.lastname: Pinto
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Av Universitária, 1105, Criciúma, 88806000, SC, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Ritter
authors.affiliation: Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Av Universitária, 1105, Criciúma, 88806000, SC, Brazil.
authors.forename: Monique
authors.initials: M
authors.lastname: Michels
authors.affiliation: Department of Electronics, Information, and Bioengineering (DEIB), Politecnico di Milano, Via Ponzio 34/5, 20133, Milan, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Gambarotta
authors.affiliation: Department of Electronics, Information, and Bioengineering (DEIB), Politecnico di Milano, Via Ponzio 34/5, 20133, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferrario
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK.|Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Av Universitária, 1105, Criciúma, 88806000, SC, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.affiliation: Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Cruciform Building, Gower Street, London, WC1E 6BT, UK. m.singer@ucl.ac.uk.
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D006728:Hormones / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053208:Kaplan-Meier Estimate; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D000073039:Nitrosative Stress; D018384:Oxidative Stress; D017208:Rats, Wistar; D012377:Rodentia; D018805:Sepsis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006728:Hormones
keywords: Autonomic nervous system; Contractility; Encephalopathy; Heart rate variability; Inflammation; Sepsis