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

Juan N. Pulido, James R. Neal, Carlos B. Mantilla, Shvetank Agarwal, Won Yeon Lee, Phillip D. Scott, Rolf D. Hubmayr, Wen Zhi Zhan, Gary C. Sieck, Gianrico Farrugia, Mark H. Ereth

Research output: Contribution to journalArticle

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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-〈) 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 ≤?.001) and oxyhemoglobin saturation (p ≤?.01) in Air versus CO treated groups, respectively. Serum TNF-〈 ?(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 com pared 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.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalJournal of Extra-Corporeal Technology
Volume43
Issue number3
StatePublished - Sep 1 2011

Fingerprint

Carbon Monoxide
Cardiopulmonary Bypass
Cytokines
Air
Interleukin-10
Real-Time Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Carboxyhemoglobin
Gene Expression
Lung
Oxyhemoglobins
Lung Injury
Mechanics
Serum
Heme
Sprague Dawley Rats
Animal Models
Hemodynamics
Enzyme-Linked Immunosorbent Assay
Oxygen

Keywords

  • Carbon monoxide
  • Cardiopulmonary bypass
  • Cytokines
  • Inflammation
  • Rat

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Health Professions (miscellaneous)
  • Cardiology and Cardiovascular Medicine

Cite this

Pulido, J. N., Neal, J. R., Mantilla, C. B., Agarwal, S., Lee, W. Y., Scott, P. D., ... Ereth, M. H. (2011). Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass. Journal of Extra-Corporeal Technology, 43(3), 137-143.

Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass. / Pulido, Juan N.; Neal, James R.; Mantilla, Carlos B.; Agarwal, Shvetank; Lee, Won Yeon; Scott, Phillip D.; Hubmayr, Rolf D.; Zhan, Wen Zhi; Sieck, Gary C.; Farrugia, Gianrico; Ereth, Mark H.

In: Journal of Extra-Corporeal Technology, Vol. 43, No. 3, 01.09.2011, p. 137-143.

Research output: Contribution to journalArticle

Pulido, JN, Neal, JR, Mantilla, CB, Agarwal, S, Lee, WY, Scott, PD, Hubmayr, RD, Zhan, WZ, Sieck, GC, Farrugia, G & Ereth, MH 2011, 'Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass', Journal of Extra-Corporeal Technology, vol. 43, no. 3, pp. 137-143.
Pulido, Juan N. ; Neal, James R. ; Mantilla, Carlos B. ; Agarwal, Shvetank ; Lee, Won Yeon ; Scott, Phillip D. ; Hubmayr, Rolf D. ; Zhan, Wen Zhi ; Sieck, Gary C. ; Farrugia, Gianrico ; Ereth, Mark H. / Inhaled carbon monoxide attenuates myocardial inflammatory cytokine expression in a rat model of cardiopulmonary bypass. In: Journal of Extra-Corporeal Technology. 2011 ; Vol. 43, No. 3. pp. 137-143.
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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-〈) 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 ≤?.001) and oxyhemoglobin saturation (p ≤?.01) in Air versus CO treated groups, respectively. Serum TNF-〈 ?(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 com pared 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.",
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N2 - 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-〈) 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 ≤?.001) and oxyhemoglobin saturation (p ≤?.01) in Air versus CO treated groups, respectively. Serum TNF-〈 ?(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 com pared 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.

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