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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2011;4(1):53-66
Original Article
Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis
Vasilios P Koulouras, Ren Li, Luni Chen, Göran G. Hedenstierna
Research Department, Department of Medical Sciences, Clinical Physiology, University Hospital, Uppsala University, Sweden;
Department of Intensive care medicine, University hospital of Ioannina, Ioannina Greece; Department of pathology, Air Force General
Hospital, Beijing, China.
Received December 27, 2010; accepted January 29, 2011; Epub February 6, 2011; published February 28, 2011
Abstract: Background: Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide
(iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether
iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential
anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis. Methods:
Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control
group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours
after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocortisone
bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics,
blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the experiment
lung tissue was taken for analysis of histology and inflammatory markers: tumor necrosis factor-alpha (TNF-α),
nuclear factor kappa B (NF-kappaB), activator protein-1 (AP-1) and glucocorticoid receptor (GR). Results: LPS administration
induced a dramatic inflammatory injury in lungs, increased expression of TNF-α, NF-kappaB, AP-1, down regulation of
GR, pulmonary hypertension and severe deterioration of respiratory mechanics, oxygenation and organ function.
Treatment with steroids and to greater extent with iCO significantly improved the microscopic appearance of the lung
but had no effect on inflammatory markers. iCO significantly decreased pulmonary hypertension induced by LPS,
without an obvious protective effect on organ function. Conclusion: Using this porcine sepsis model we find that
treatment with iCO after the septic damage decreases pulmonary hypertension and partially protects the lung tissue
from the inflammatory destruction induced by LPS but has no beneficial effects on organ function. (IJCEM1012005).
Keywords: Carbon monoxide, steroids, porcine sepsis model, acute lung injury, organ function.
Full Text PDF
Address all correspondence to:
Vasilios P Koulouras, MD, PhD
University Hospital of Ioannina
Dpt of Intensive Care
Avenue: S. Niarchos
45500 Greece.
E-mail: vpkoulouras@yahoo.gr
Original Article
Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis
Vasilios P Koulouras, Ren Li, Luni Chen, Göran G. Hedenstierna
Research Department, Department of Medical Sciences, Clinical Physiology, University Hospital, Uppsala University, Sweden;
Department of Intensive care medicine, University hospital of Ioannina, Ioannina Greece; Department of pathology, Air Force General
Hospital, Beijing, China.
Received December 27, 2010; accepted January 29, 2011; Epub February 6, 2011; published February 28, 2011
Abstract: Background: Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide
(iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether
iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential
anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis. Methods:
Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control
group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours
after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocortisone
bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics,
blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the experiment
lung tissue was taken for analysis of histology and inflammatory markers: tumor necrosis factor-alpha (TNF-α),
nuclear factor kappa B (NF-kappaB), activator protein-1 (AP-1) and glucocorticoid receptor (GR). Results: LPS administration
induced a dramatic inflammatory injury in lungs, increased expression of TNF-α, NF-kappaB, AP-1, down regulation of
GR, pulmonary hypertension and severe deterioration of respiratory mechanics, oxygenation and organ function.
Treatment with steroids and to greater extent with iCO significantly improved the microscopic appearance of the lung
but had no effect on inflammatory markers. iCO significantly decreased pulmonary hypertension induced by LPS,
without an obvious protective effect on organ function. Conclusion: Using this porcine sepsis model we find that
treatment with iCO after the septic damage decreases pulmonary hypertension and partially protects the lung tissue
from the inflammatory destruction induced by LPS but has no beneficial effects on organ function. (IJCEM1012005).
Keywords: Carbon monoxide, steroids, porcine sepsis model, acute lung injury, organ function.
Full Text PDF
Address all correspondence to:
Vasilios P Koulouras, MD, PhD
University Hospital of Ioannina
Dpt of Intensive Care
Avenue: S. Niarchos
45500 Greece.
E-mail: vpkoulouras@yahoo.gr
