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Does Hypercapnia Ameliorate Hyperoxia-Induced Lung Injury in Neonatal Rats?

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Abstract

Therapeutic hypercapnia (TH), an intentional inhalation of CO2, has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children’s Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO2 = 0.21), hyperoxia (FiO2 > 0.98), and TH (FiO2 = 0.95, FiCO2 = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0–4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P < 0.05) and 3.0 with TH (P < 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P < 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P < 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1β compared with normoxia (P < 0.001), whereas the ratio of IL-1β to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.

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References

  1. Warner BB, Stuart LA, Papes RA, Wispe JR (1998) Functional and pathological effects of prolonged hyperoxia on neonatal mice. Am J Physiol 275:L110–L117

    CAS  PubMed  Google Scholar 

  2. Coalson JJ, Winter VT, Siler-Khodr T, Yoder BA (1999) Neonatal chronic lung disease in extremely immature baboons. Am J Respir Crit Care Med 160:1333–1346

    CAS  PubMed  Google Scholar 

  3. Sinclair SE, Altemeier WA, Matute-Bello G, Chi EY (2004) Augmented lung injury due to interaction between hyperoxia and mechanical ventilation. Crit Care Med 32:2496–2501

    Article  PubMed  Google Scholar 

  4. Torbati D, Tan GH, Smith S, Frazier KS, Gelvez J, Fakioglu H, Totapally BR (2006) Multiple organ effects of normobaric hyperoxia in neonatal rats. J Crit Care 21:85–94

    Article  PubMed  Google Scholar 

  5. Ballard PL, Gonzales LW, Godinez RI, Godinez MH, Savani RC, McCurini DC, Gibson LL, Yoder BA, Kerecman JD, Grubb PH, Shaul PW (2006) Surfactant composition and function in a primate model of infant chronic lung disease: effect of inhaled nitric oxide. Pediatr Res 59:157–162

    Article  CAS  PubMed  Google Scholar 

  6. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Olivera R, Takagaki TY, Carvalho CR (1998) Effects of a protective-ventilation strategy on mortality in the Acute Respiratory Distress Syndrome. N Engl J Med 338:347–354

    Article  CAS  PubMed  Google Scholar 

  7. Broccard AF, Hotchkiss JR, Vannay C, Markert M, Sauty A, Feihl F, Schaller MD (2001) Protective effects of hypercapnic acidosis on ventilation-induced lung injury. Am J Respir Crit Care Med 164:802–806

    CAS  PubMed  Google Scholar 

  8. Sinclair SE, Kregenow DA, Lamm WJ, Starr IR, Chi EY, Hlastala MP (2002) Hypercapnic acidosis is protective in an in vivo model of ventilation-induced lung injury. Am J Resp Crit Care Med 166:403–408

    Article  PubMed  Google Scholar 

  9. Strand M, Ikegami M, Jobe AH (2003) Effects of high PCO2 on ventilated preterm lamb lungs. Pediatr Res 53:468–472

    Article  PubMed  Google Scholar 

  10. Laffey JG, Engelberts D, Duggan M, Veldhuizen R, Lewis JF, Kavanagh BP (2003) Carbon dioxide attenuates pulmonary impairment resulting from hyperventilation. Crit Care Med 31:2634–2640

    Article  PubMed  Google Scholar 

  11. Laffey JG, Honan D, Hopkins N, Hyvelin JM, Boylan JF, McLoughlin P (2004) Hypercapnic acidosis attenuates endotoxin-induced lung injury. Am J Resp Crit Care Med 169:46–56

    Article  PubMed  Google Scholar 

  12. Kantores C, McNamara PJ, Teixeira L, Engelberts D, Murphy P, Kavanagh BP, Jankov RP (2006) Therapeutic hypercapnia prevents chronic hypoxia-induced pulmonary hypertension in the newborn rat. Am J Physiol Lung Cell Mol Physiol 291:L912–L922

    Article  CAS  PubMed  Google Scholar 

  13. Swenson ER, Robertson HT, Hlastala P (1994) Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia. Am J Respir Crit Care Med 149:1563–1569

    CAS  PubMed  Google Scholar 

  14. Ramirez J, Totapally BR, Hon E, Mangino MJ, Hultquist KA, Wolfsdorf J (2000) Oxygen carrying capacity during 10 hours of hypercapnia in ventilated dogs. Crit Care Med 28:1918–1923

    Article  CAS  PubMed  Google Scholar 

  15. Torbati D, Totapally BR, Camacho MT, Wolfsdorf J (1999) Experimental critical care in ventilated rats: effect of hypercapnia on arterial oxygen carrying capacity. J Crit Care 14:191–197

    Article  CAS  PubMed  Google Scholar 

  16. Rai S, Engelberts D, Laffey JG, Frevert C, Kajikawa O, Martin TR, Post M, Kavanagh BP (2003) Therapeutic hypercapnia is not protective in the in vivo surfactant-depleted rabbit lung. Pediatr Res 55:42–49

    Article  PubMed  Google Scholar 

  17. Bouvet F, Dreyfuss D, Lebtahi R, Martet G, Le Guludec D, Saumon G (2005) Noninvasive evaluation of acute capillary permeability changes during high volume ventilation in rats with and without hypercapnic acidosis. Crit Care Med 33:155–160

    Article  PubMed  Google Scholar 

  18. Doerr CH, Gajic O, Berrios JC, Caples S, Abdel M, Lymp JF, Hubmayer RD (2005) Hypercapnic acidosis impairs plasma membrane wound resealing in ventilator-injured lungs. Am J Resp Crit Care Med 171:1371–1377

    Article  PubMed  Google Scholar 

  19. Lang JD, Figueroa M, Sanders KD, Aslan M, Liu Y, Chumley P, Freeman BA (2005) Hypercapnia via reduced rate and tidal volume contributes to lipopolysaccharide-induced lung injury. Am J Resp Crit Care Med 17:147–157

    Google Scholar 

  20. O’Croinin DF, Nichol AD, Hopkins NO, Boylan J, O’Brien S, O’Connor C, Laffey JG, McLoughin P (2008) Sustain hypercapnic acidosis during pulmonary infection increases bacterial load and worsen lung injury. Crit Care Med 36:2209–2235

    Article  Google Scholar 

  21. Checchin D, Sennlaup F, Sirinyan M, Brault S, Zhu T, Kermorvant-Duchemin E, Hardy P, Balazy M, Chemtob S (2006) Hypercapnia prevents neovascularization via nitrative stress. Free Radic Biol Med 40:543–553

    Article  CAS  PubMed  Google Scholar 

  22. Chonghaile MN, Higgins BD, Costello J, Laffey JG (2008) Hypercapnic acidosis attenuates lung injury induced by established bacterial pneumonia. Anesthesiology 109:771–772

    Article  Google Scholar 

  23. Vesela A, Wilhelm J (2002) The role of carbon dioxide in free radical reactions of the organism. Physiol Res 51:335–339

    CAS  PubMed  Google Scholar 

  24. Liochev SI, Fridovich I (2004) Carbon dioxide mediates Mn-catalyzed decomposition of hydrogen peroxide and peroxidation reactions. Proc Natl Acad Sci USA 101:12485–12490

    Article  CAS  PubMed  Google Scholar 

  25. Uppu RM, Nossaman BD, Greco AJ, Fokin A, Murthy SN, Fonseca VA, Kadowitz PJ (2007) Cardiovascular effects of peroxynitrite. Clin Exp Pharmacol Physiol 34:933–937

    Article  CAS  PubMed  Google Scholar 

  26. Yi M, Jankov RP, Belcastro R, Humes D, Copland I, Shek S, Sweezey NB, Post M, Albertine KH, Auten RL, Tanswell AR (2004) Opposing effects of 80% oxygen and neutrophil influx on alveogenesis in the neonatal rat. Am J Respir Crit Care Med 170:1188–1196

    Article  PubMed  Google Scholar 

  27. Speer CP (2006) Pulmonary inflammation and bronchopulmonary dysplasia. J Perinatal 26(Suppl 1):S57–S62

    Article  CAS  Google Scholar 

  28. Johnston CJ, Wright TW, Reed CK, Finkelstein JN (1997) Comparison of adult and newborn pulmonary cytokine mRNA expression after hyperoxia. Exp Lung Res 23:537–552

    Article  CAS  PubMed  Google Scholar 

  29. Ben-Ari J, Makhoul IR, Dorio RJ, Buckley S, Warburton D, Walker SM (2000) Cytokine response during hyperoxia: sequential production of pulmonary tumor necrosis factor and interleukin-6 in neonatal rats. Isr Med Associ J 2:365–369

    CAS  Google Scholar 

  30. Bhandari V (2002) Developmental differences in the role of interleukins in hyperoxic lung injury in animal models. Front Biosci 7d:1624–1633

    Article  Google Scholar 

  31. Bhandari V, Elias JA (2006) Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. Free Radic Biol Med 41:4–18

    Article  CAS  PubMed  Google Scholar 

  32. D’Angio CT, Johnston CJ, Wright TW, Reed CK, Finkelstein JN (1998) Chemokine mRNA alterations in newborn and adult mouse lung during acute hyperoxia. Exp Lung Res 24:685–702

    Article  PubMed  Google Scholar 

  33. Frank L (1991) Hyperoxic inhibition of newborn rat lung development: protection by deferoxamine. Free Radic Biol Med 11:341–348

    Article  CAS  PubMed  Google Scholar 

  34. Jankov RP, Tanswell AK (2008) Hypercapnia and the neonate. Acta Paediatr 97:1502–1509

    Article  PubMed  Google Scholar 

  35. Vanker M, Haltbertsma FJ, van Egmond J, Netea MG, Dijkman HB, Snijdelaar DG et al (2007) Mechanical ventilation in healthy mice induces reversible pulmonary and systemic cytokine elevation with preserved alveolar integrity: an in vivo model using clinical relevant ventilation settings. Anesthesiology 107:419–426

    Article  Google Scholar 

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Acknowledgment

Supported by Alex Simberg’s Fund for Critical Care Medicine.

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Authors and Affiliations

  1. Division of Critical Care Medicine, Miami Children’s Hospital, 3100 SW 62nd Avenue, Miami, FL, 33155, USA

    Matthew J. MacCarrick, Dan Torbati, Dai Kimura, Andre Raszynski, Wenjing Zeng & Balagangadhar R. Totapally

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  1. Matthew J. MacCarrick
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  2. Dan Torbati
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  3. Dai Kimura
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  4. Andre Raszynski
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  5. Wenjing Zeng
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  6. Balagangadhar R. Totapally
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Correspondence to Dan Torbati.

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MacCarrick, M.J., Torbati, D., Kimura, D. et al. Does Hypercapnia Ameliorate Hyperoxia-Induced Lung Injury in Neonatal Rats?. Lung 188, 235–240 (2010). https://doi.org/10.1007/s00408-009-9211-1

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  • DOI: https://doi.org/10.1007/s00408-009-9211-1

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