Michaela Kohoutova1,2, Jan Horak2,3, Dagmar Jarkovska1,2, Vendula Martinkova2,4, Vaclav Tegl2,5, Lukas Nalos1,2, Lucie Vistejnova2, Jan Benes2,5, Jitka Sviglerova1,2, Jitka Kuncova1,2, Martin Matejovic2,3, Milan Stengl1,2. 1. Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. 2. Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. 3. Department of Internal Medicine I, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic. 4. Third Department of Surgery, University Hospital Motol and First Medical School, Charles University, Prague, Czech Republic. 5. Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Abstract
OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS: Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.
OBJECTIVES: To investigate the potential benefits of vagus nerve stimulation in a clinically-relevant large animal model of progressive sepsis. DESIGN: Prospective, controlled, randomized trial. SETTING: University animal research laboratory. SUBJECTS: Twenty-five domestic pigs were divided into three groups: 1) sepsis group (eight pigs), 2) sepsis + vagus nerve stimulation group (nine pigs), and 3) control sham group (eight pigs). INTERVENTIONS:Sepsis was induced by cultivated autologous feces inoculation in anesthetized, mechanically ventilated, and surgically instrumented pigs and followed for 24 hours. Electrical stimulation of the cervical vagus nerve was initiated 6 hours after the induction of peritonitis and maintained throughout the experiment. MEASUREMENTS AND MAIN RESULTS: Measurements of hemodynamics, electrocardiography, biochemistry, blood gases, cytokines, and blood cells were collected at baseline (just before peritonitis induction) and at the end of the in vivo experiment (24 hr after peritonitis induction). Subsequent in vitro analyses addressed cardiac contractility and calcium handling in isolated tissues and myocytes and analyzed mitochondrial function by ultrasensitive oxygraphy. Vagus nerve stimulation partially or completely prevented the development of hyperlactatemia, hyperdynamic circulation, cellular myocardial depression, shift in sympathovagal balance toward sympathetic dominance, and cardiac mitochondrial dysfunction, and reduced the number of activated monocytes. Sequential Organ Failure Assessment scores and vasopressor requirements significantly decreased after vagus nerve stimulation. CONCLUSIONS: In a clinically-relevant large animal model of progressive sepsis, vagus nerve stimulation was associated with a number of beneficial effects that resulted in significantly attenuated multiple organ dysfunction and reduced vasopressor and fluid resuscitation requirements. This suggests that vagus nerve stimulation might provide a significant therapeutic potential that warrants further thorough investigation.
Authors: Mahmoud Al-Obeidallah; Dagmar Jarkovská; Lenka Valešová; Jan Horák; Jan Jedlička; Lukáš Nalos; Jiří Chvojka; Jitka Švíglerová; Jitka Kuncová; Jan Beneš; Martin Matějovič; Milan Štengl Journal: J Pers Med Date: 2021-02-28
Authors: Carlos Tornero; Ernesto Pastor; María Del Mar Garzando; Jorge Orduña; Maria J Forner; Irene Bocigas; David L Cedeño; Ricardo Vallejo; Candace K McClure; Christopher J Czura; Eric J Liebler; Peter Staats Journal: Front Neurol Date: 2022-04-08 Impact factor: 4.003
Authors: Rishabh C Choudhary; Umair Ahmed; Muhammad Shoaib; Eric Alper; Abdul Rehman; Junhwan Kim; Koichiro Shinozaki; Bruce T Volpe; Sangeeta Chavan; Stavros Zanos; Kevin J Tracey; Lance B Becker Journal: Bioelectron Med Date: 2022-07-20