Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass

J Extra Corpor Technol. 2011 Sep;43(3):137-43.

Abstract

Carbon monoxide (CO), a by-product of Heme metabolism, is a potent modulator of inflammation. Low dose inhaled CO has demonstrated reduced lung and kidney injury in animal models of cardiopulmonary bypass (CPB). We evaluated the impact of low dose inhaled CO on systemic, pulmonary, and myocardial inflammatory response to CPB in rats. Sixteen male Sprague-Dawley rats underwent CPB for 1 hour. The CO (n = 8) group received inhaled CO at 250 ppm for 3 hours before CPB. The Air (n = 8) group served as the control. Pulmonary mechanics were assessed pre and post CPB. The animals were recovered for 30 minutes post CPB and subsequently sacrificed. Pre CPB and post CPB serum Tumor Necrosis Factor-alpha (TNF-alpha) and Interleukin-10 (IL-10) were analyzed by enzyme-linked immunosorbent assay. Gene expression array and real time quantitative polymerase chain reaction (PCR) analysis was performed on the extracted heart tissue. Baseline characteristics were similar between the groups with the expected exception of carboxyhemoglobin levels (p < or = .001) and oxyhemoglobin saturation (p < or = .01) in Air versus CO treated groups, respectively. Serum TNF-alpha (363 +/- 278 vs. 287 +/- 195;p = .13) and IL-10 (237 +/- 26 vs. 302 +/- 137; p = Not Significant) in Air versus CO groups respectively were not statistically different after CPB, despite showing a trend of inflammatory attenuation. Gene expression array of the myocardial tissue suggested a pattern of inflammatory modulation, which was confirmed by real time quantitative PCR demonstrating IL-10 expression 3.13 times higher (p = .02) in the CO treated group compared to the Air group. These data demonstrate that pretreatment with CO at 250 ppm may have a modulatory effect on the inflammatory response to CPB without compromising hemodynamics or oxygen delivery. Further investigation in a survival model of CPB is warranted.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Animals
  • Carbon Monoxide / administration & dosage*
  • Carbon Monoxide / pharmacology
  • Cardiopulmonary Bypass*
  • Enzyme-Linked Immunosorbent Assay
  • Interleukin-10 / metabolism*
  • Male
  • Myocardium / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Carbon Monoxide