Differential Effects of Buffered Hypercapnia Versus Hypercapnic Acidosis on Shock and Lung Injury Induced by Systemic Sepsis

2010 ◽  
Vol 54 (5) ◽  
pp. 216
Author(s):  
&NA;
2009 ◽  
Vol 111 (6) ◽  
pp. 1317-1326 ◽  
Author(s):  
Brendan D. Higgins ◽  
Joseph Costello ◽  
Maya Contreras ◽  
Patrick Hassett ◽  
Daniel O' Toole ◽  
...  

Background Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis. Methods In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis-produced by adding 5% carbon dioxide to the inspired gas-and cecal ligation and puncture performed. In the buffered hypercapnia series, animals were first randomized to housing under conditions of environmental normocapnia or hypercapnia-produced by exposure to 8% carbon dioxide-to allow renal buffering. After 96 h, cecal ligation and puncture was performed. In both series, the animals were ventilated for 6 h, and the severity of the lung injury and hemodynamic deterioration were assessed. Results Both hypercapnic acidosis and buffered hypercapnia attenuated the development and severity of hypotension and reduced lactate accumulation compared to normocapnia. Hypercapnic acidosis reduced lung injury and inflammation, decreased mean (+ or - SD) bronchoalveolar lavage protein concentration (232 + or - 50 versus 279 + or - 27 microg x ml(-1)) and median neutrophil counts (3,370 versus 9,120 cells x ml(-1)), and reduced histologic lung injury. In contrast, buffered hypercapnia did not reduce the severity of systemic sepsis induced lung injury. Conclusions Both hypercapnic acidosis and buffered hypercapnia attenuate the hemodynamic consequences of systemic sepsis. In contrast, hypercapnic acidosis, but not buffered hypercapnia, reduced the severity of sepsis-induced lung injury.


2009 ◽  
Vol 37 (8) ◽  
pp. 2412-2420 ◽  
Author(s):  
Joseph Costello ◽  
Brendan Higgins ◽  
Maya Contreras ◽  
Martina Ni Chonghaile ◽  
Patrick Hassett ◽  
...  

1997 ◽  
Vol 22 (5) ◽  
pp. 901-908 ◽  
Author(s):  
Timothy P Ryan ◽  
Raymond F Krzesicki ◽  
David P Blakeman ◽  
Jia En Chin ◽  
Robert L Griffin ◽  
...  

2008 ◽  
Vol 36 (12) ◽  
pp. 3268-3269
Author(s):  
Mario Perl ◽  
Markus Huber-Lang ◽  
Peter Radermacher

2012 ◽  
Vol 40 (9) ◽  
pp. 2622-2630 ◽  
Author(s):  
Maya Contreras ◽  
Bilal Ansari ◽  
Gerard Curley ◽  
Brendan D. Higgins ◽  
Patrick Hassett ◽  
...  

Author(s):  
Jennifer K Trittmann ◽  
Yi Jin ◽  
Yusen Liu ◽  
Leif D. Nelin

Endothelial cell apoptosis is an early event in the development of acute lung injury (ALI). We have previously found that the Src family tyrosine kinase (STK) yes activates caspase-3, while the STK fyn inhibits caspase-3 activation in cultured pulmonary endothelial cells. We hypothesized that deficiency in yes or fyn in mice would have differential effects on lipopolysaccharide (LPS)-induced ALI. Mice were treated with 10 mg/kg LPS i.p. for 24 hours. Histological evidence of lung injury was greater in LPS-treated wild-type mice than in vehicle treated wild-type mice, and the LPS-induced histological evidence of lung injury were attenuated in yes-/- mice and enhanced in fyn-/- mice. In wild-type or fyn-/- mice LPS resulted in greater lung wet-to-dry weight ratios than in controls, while in yes-/- mice lung wet-to-dry weight was similar between LPS and controls. LPS-exposed fyn-/- mice had greater respiratory system resistance and lower respiratory system compliance than did LPS-exposed wild-type mice. TUNEL positive cells in the lung following LPS treatment were greater in the fyn-/- mice and lower in the yes-/- mice compared to that in the wild-type mice. Following LPS treatment lung protein levels of PECAM-1 were lower in fyn-/- mice than in controls or yes-/- mice. LPS treatment increased cleaved caspase-3 protein levels in wild-type mice, while LPS-induced caspase-3 activation was attenuated in yes-/- mice and enhanced in fyn-/- mice. These results indicate that LPS-induced ALI is positively mediated via yes related mechanisms and negatively mediated by fyn related mechanisms.


2011 ◽  
Vol 17 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Alexander B. Benson ◽  
James R. Burton ◽  
Gregory L. Austin ◽  
Scott W. Biggins ◽  
Michael A. Zimmerman ◽  
...  

2000 ◽  
Vol 161 (1) ◽  
pp. 141-146 ◽  
Author(s):  
JOHN G. LAFFEY ◽  
DOREEN ENGELBERTS ◽  
BRIAN P. KAVANAGH

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