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Nonrespiratory Functions of the Lung

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Principles and Practice of Anesthesia for Thoracic Surgery

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Abstract

Pulmonary endothelial cells metabolize endogenous substances and xenobiotics via ectoenzymes on their luminal surface and caveolae as well as enzyme systems within the cytosol. Pulmonary metabolism results in the activation of several endogenous substances and medications of importance to the anesthesiologist. Pulmonary uptake is often not associated with metabolism, but still markedly affects pharmacokinetics by initially attenuating peak concentrations before ultimately returning the unchanged substance to the circulation. The lung’s ability to serve as a vascular reservoir is directly related to the capacitance of the pulmonary vessels. The lung serves as a physical filter, but this function may be compromised with high cardiac output and in several disease states. The respiratory epithelium’s functions include humidification and trapping of particles and pathogens. The airway surface film has antimicrobial capacity beyond its mechanical removal of debris from the airway.

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References

  1. Major R. A history of medicine. Springfield: Thomas; 1954.

    Google Scholar 

  2. Lumb AB. The history of respiratory physiology. In: Lumb AB, editor. Nunn’s applied respiratory physiology. 6th ed. Oxford: Buttterworth-Heinemann; 2005.

    Google Scholar 

  3. Shoja MM, Tubbs RS. The history of anatomy in Persia. J Anat. 2007;210(4):359–78.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Simionescu M. Lung endothelium: structure-function correlates. In: Crystal RG, editor. Lung: scientific foundations. New York: Raven Press; 1991. p. 301–21.

    Google Scholar 

  5. Klein IK, Predescu DN, Sharma T, Knezevic I, Malik AB, Predescu S. Intersectin-2L regulates caveola endocytosis secondary to Cdc42-mediated actin polymerization. J Biol Chem. 2009;284(38):25953–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Parat M, Kwang WJ. The biology of caveolae: achievements and perspectives. In: International review of cell and molecular biology, vol. 273. Amsterdam: Academic; 2009. p. 117–62.

    Google Scholar 

  7. Ryan US, Ryan JW. Relevance of endothelial surface structure to the activity of vasoactive substances. Chest. 1985;88(4 Suppl):203S–7.

    Article  CAS  PubMed  Google Scholar 

  8. Ryan JW, Smith U. Metabolism of adenosine 5′-monophosphate during circulation through the lungs. Trans Assoc Am Phys. 1971;84:297–306.

    CAS  PubMed  Google Scholar 

  9. Vane JR. The release and fate of vaso-active hormones in the circulation. Br J Pharmacol. 1969;35(2):209–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Dawidowicz ALP, Fornal EPD, Mardarowicz MPD, Fijalkowska APD. The role of human lungs in the biotransformation of propofol. Anesthesiology. 2000;93(4):992–7.

    Article  CAS  PubMed  Google Scholar 

  11. Hiraoka H, Yamamoto K, Miyoshi S, et al. Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain. Br J Clin Pharmacol. 2005;60(2):176–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. de Graaf IAM, Koster HJ. Cryopreservation of precision-cut tissue slices for application in drug metabolism research. Toxicol In Vitro. 2003;17(1):1–17.

    Article  PubMed  Google Scholar 

  13. Klem C, Dasta JF, Reilley TE, Flancbaum LJ. Pulmonary extraction of dobutamine in critically ill surgical patients. Anesth Analg. 1995;81(2):287–91.

    CAS  PubMed  Google Scholar 

  14. Hayashi Y, Sumikawa K, Yamatodani A, Kamibayashi T, Mammoto T, Kuro M. Quantitative analysis of pulmonary clearance of exogenous dopamine after cardiopulmonary bypass in humans. Anesth Analg. 1993;76(1):107–12.

    Article  CAS  PubMed  Google Scholar 

  15. Matot I, Pizov R. Pulmonary extraction and accumulation of lipid formulations of amphotericin B. Crit Care Med. 2000;28(7):2528–32.

    Article  CAS  PubMed  Google Scholar 

  16. Upton RN, Doolette DJ. Kinetic aspects of drug disposition in the lungs. Clin Exp Pharmacol Physiol. 1999;26(5–6):381–91.

    Article  CAS  PubMed  Google Scholar 

  17. Serabjit-Singh CJ, Nishio SJ, Philpot RM, Plopper CG. The distribution of cytochrome P-450 monooxygenase in cells of the rabbit lung: an ultrastructural immunocytochemical characterization. Mol Pharmacol. 1988;33(3):279–89.

    CAS  PubMed  Google Scholar 

  18. Mizuguchi KA, Fox AA, Burch TM, Cohn LH, Fox JA. Tricuspid and mitral valve carcinoid disease in the setting of a patent foramen ovale. Anesth Analg. 2008;107(6):1819–21.

    Article  PubMed  Google Scholar 

  19. Pacifici GM, Franchi M, Bencini C, Repetti F, Di Lascio N, Muraro GB. Tissue distribution of drug-metabolizing enzymes in humans. Xenobiotica. 1988;18(7):849–56.

    Article  CAS  PubMed  Google Scholar 

  20. Litterst CL, Mimnaugh EG, Reagan RL, Gram TE. Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species. Drug Metab Dispos. 1975;3(4):259–65.

    CAS  PubMed  Google Scholar 

  21. Taeger K, Weninger E, Schmelzer F, Adt M, Franke N, Peter K. Pulmonary kinetics of fentanyl and alfentanil in surgical patients. Br J Anaesth. 1988;61(4):425–34.

    Article  CAS  PubMed  Google Scholar 

  22. Waters CM, Krejcie TC, Avram MJ. Facilitated uptake of fentanyl, but not alfentanil, by human pulmonary endothelial cells. Anesthesiology. 2000;93(3):825–31.

    Article  CAS  PubMed  Google Scholar 

  23. Boer F, Bovill JG, Burm AG, Mooren RA. Uptake of sufentanil, alfentanil and morphine in the lungs of patients about to undergo coronary artery surgery. Br J Anaesth. 1992;68(4):370–5.

    Article  CAS  PubMed  Google Scholar 

  24. Boer F, Olofsen E, Bovill JG, et al. Pulmonary uptake of sufentanil during and after constant rate infusion. Br J Anaesth. 1996;76(2):203–8.

    Article  CAS  PubMed  Google Scholar 

  25. Davis ME, Mehendale HM. Absence of metabolism of morphine during accumulation by isolated perfused rabbit lung. Drug Metab Dispos. 1979;7(6):425–8.

    CAS  PubMed  Google Scholar 

  26. Roerig DL, Kotrly KJ, Vucins EJ, Ahlf SB, Dawson CA, Kampine JP. First pass uptake of fentanyl, meperidine, and morphine in the human lung. Anesthesiology. 1987;67(4):466–72.

    Article  CAS  PubMed  Google Scholar 

  27. Persson MP, Wiklund L, Hartvig P, Paalzow L. Potential pulmonary uptake and clearance of morphine in postoperative patients. Eur J Clin Pharmacol. 1986;30(5):567–74.

    Article  CAS  PubMed  Google Scholar 

  28. Beaufort TM, Proost JH, Houwertjes MC, Roggeveld J, Wierda JM. The pulmonary first-pass uptake of five nondepolarizing muscle relaxants in the pig. Anesthesiology. 1999;90(2):477–83.

    Article  CAS  PubMed  Google Scholar 

  29. Bertler A, Lewis DH, Lofstrom JB, Post C. In vivo lung uptake of lidocaine in pigs. Acta Anaesthesiol Scand. 1978;22(5):530–6.

    Article  CAS  PubMed  Google Scholar 

  30. Post C, Eriksdotter-Behm K. Dependence of lung uptake of lidocaine in vivo on blood pH. Acta Pharmacol Toxicol (Copenh). 1982;51(2):136–40.

    Article  CAS  Google Scholar 

  31. Krejcie TC, Avram MJ, Gentry WB, Niemann CU, Janowski MP, Henthorn TK. A recirculatory model of the pulmonary uptake and pharmacokinetics of lidocaine based on analysis of arterial and mixed venous data from dogs. J Pharmacokinet Biopharm. 1997;25(2):169–90.

    Article  CAS  PubMed  Google Scholar 

  32. Hasegawa K, Yukioka H, Hayashi M, Tatekawa S, Fujimori M. Lung uptake of lidocaine during hyperoxia and hypoxia in the dog. Acta Anaesthesiol Scand. 1996;40(4):489–95.

    Article  CAS  PubMed  Google Scholar 

  33. Sjostrand U, Widman B. Distribution of bupivacaine in the rabbit under normal and acidotic conditions. Acta Anaesthesiol Scand Suppl. 1973;50:1–24.

    CAS  PubMed  Google Scholar 

  34. Irestedt L, Andreen M, Belfrage P, Fagerstrom T. The elimination of bupivacaine (Marcain) after short intravenous infusion in the dog: with special reference to the role played by the liver and lungs. Acta Anaesthesiol Scand. 1978;22(4):413–22.

    Article  CAS  PubMed  Google Scholar 

  35. Rothstein P, Cole JS, Pitt BR. Pulmonary extraction of [3H]bupivacaine: modification by dose, propranolol and interaction with [14C]5-hydroxytryptamine. J Pharmacol Exp Ther. 1987;240(2):410–4.

    CAS  PubMed  Google Scholar 

  36. Kietzmann D, Foth H, Geng WP, Rathgeber J, GundertRemy U, Kettler D. Transpulmonary disposition of prilocaine, mepivacaine, and bupivacaine in humans in the course of epidural anaesthesia. Acta Anaesthesiol Scand. 1995;39(7):885–90.

    Article  CAS  PubMed  Google Scholar 

  37. Sharrock NE, Mather LE, Go G, Sculco TP. Arterial and pulmonary arterial concentrations of the enantiomers of bupivacaine after epidural injection in elderly patients. Anesth Analg. 1998;86(4):812–7.

    Article  CAS  PubMed  Google Scholar 

  38. Palazzo MG, Kalso EA, Argiras E, Madgwick R, Sear JW. First pass lung uptake of bupivacaine: effect of acidosis in an intact rabbit lung model. Br J Anaesth. 1991;67(6):759–63.

    Article  PubMed  Google Scholar 

  39. Chang DH, Ladd LA, Wilson KA, Gelgor L, Mather LE. Tolerability of large-dose intravenous levobupivacaine in sheep. Anesth Analg. 2000;91(3):671–9.

    Article  CAS  PubMed  Google Scholar 

  40. Ohmura S, Kawada M, Ohta T, Yamamoto K, Kobayashi T. Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.[see comment]. Anesth Analg. 2001;93(3):743–8.

    Article  CAS  PubMed  Google Scholar 

  41. Ohmura S, Sugano A, Kawada M, Yamamoto K. Pulmonary uptake of ropivacaine and levobupivacaine in rabbits. Anesth Analg. 2003;97(3):893–7.

    Article  CAS  PubMed  Google Scholar 

  42. Mather LE, Copeland SE, Ladd LA. Acute toxicity of local anesthetics: underlying pharmacokinetic and pharmacodynamic concepts [see comment]. Reg Anesth Pain Med. 2005;30(6):553–66.

    CAS  PubMed  Google Scholar 

  43. Heavner JE. Let’s abandon blanket maximum recommended doses of local anesthetics [comment]. Reg Anesth Pain Med. 2004;29(6):524.

    PubMed  Google Scholar 

  44. Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactorial concept [see comment]. Reg Anesth Pain Med. 2004;29(6):564–75; discussion 524.

    CAS  PubMed  Google Scholar 

  45. Reynolds F. Maximum recommended doses of local anesthetics: a constant cause of confusion [comment]. Reg Anesth Pain Med. 2005;30(3):314–6.

    PubMed  Google Scholar 

  46. Groban L. Central nervous system and cardiac effects from long-acting amide local anesthetic toxicity in the intact animal model. Reg Anesth Pain Med. 2003;28(1):3–11.

    Article  CAS  PubMed  Google Scholar 

  47. Mulroy MF. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive measures. Reg Anesth Pain Med. 2002;27(6):556–61.

    Article  CAS  PubMed  Google Scholar 

  48. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest [see comment]. Anesthesiology. 2006;105(1):217–8.

    Article  PubMed  Google Scholar 

  49. Felice K, Schumann H. Intravenous lipid emulsion for local anesthetic toxicity: a review of the literature. J Med Toxicol. 2008;4(3):184–91.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest [see comment]. Anesth Analg. 2009;108(4):1344–6.

    Article  CAS  PubMed  Google Scholar 

  51. Roerig DL, Kotrly KJ, Dawson CA, Ahlf SB, Gualtieri JF, Kampine JP. First-pass uptake of verapamil, diazepam, and thiopental in the human lung. Anesth Analg. 1989;69(4):461–6.

    Article  CAS  PubMed  Google Scholar 

  52. Pedraz JL, Lanao JM, Hernandez JM, Dominguez-Gil A. The biotransformation kinetics of ketamine “in vitro” in rabbit liver and lung microsome fractions. Eur J Drug Metab Pharmacokinet. 1986;11(1):9–16.

    Article  CAS  PubMed  Google Scholar 

  53. Henthorn TK, Krejcie TC, Niemann CU, Enders-Klein C, Shanks CA, Avram MJ. Ketamine distribution described by a recirculatory pharmacokinetic model is not stereoselective. Anesthesiology. 1999;91(6):1733–43.

    Article  CAS  PubMed  Google Scholar 

  54. Mather LE, Selby DG, Runciman WB, McLean CF. Propofol: assay and regional mass balance in the sheep. Xenobiotica. 1989;19(11):1337–47.

    Article  CAS  PubMed  Google Scholar 

  55. Kuipers JA, Boer F, Olieman W, Burm AG, Bovill JG. First-pass lung uptake and pulmonary clearance of propofol: assessment with a recirculatory indocyanine green pharmacokinetic model. Anesthesiology. 1999;91(6):1780–7.

    Article  CAS  PubMed  Google Scholar 

  56. Matot I, Neely CF, Katz RY, Neufeld GR. Pulmonary uptake of propofol in cats. Effect of fentanyl and halothane. Anesthesiology. 1993;78(6):1157–65.

    Article  CAS  PubMed  Google Scholar 

  57. Le Guellec C, Lacarelle B, Villard PH, Point H, Catalin J, Durand A. Glucuronidation of propofol in microsomal fractions from various tissues and species including humans: effect of different drugs. Anesth Analg. 1995;81(4):855–61.

    CAS  PubMed  Google Scholar 

  58. Bulger EM, Maier RV. Lipid mediators in the pathophysiology of critical illness. Crit Care Med. 2000;28(4 Suppl):N27–36.

    Article  CAS  PubMed  Google Scholar 

  59. Upton RN, Ludbrook G. A physiologically based, recirculatory model of the kinetics and dynamics of propofol in man. Anesthesiology. 2005;103(2):344–52.

    Article  CAS  PubMed  Google Scholar 

  60. Kazama T, Ikeda K, Morita K, Ikeda T, Kikura M, Sato S. Relation between initial blood distribution volume and propofol induction dose requirement [see comment]. Anesthesiology. 2001;94(2):205–10.

    Article  CAS  PubMed  Google Scholar 

  61. Kazama T, Morita K, Ikeda T, Kurita T, Sato S. Comparison of predicted induction dose with predetermined physiologic characteristics of patients and with pharmacokinetic models incorporating those characteristics as covariates. Anesthesiology. 2003;98(2):299–305.

    Article  CAS  PubMed  Google Scholar 

  62. Krejcie TC, Jacquez JA, Avram MJ, Niemann CU, Shanks CA, Henthorn TK. Use of parallel Erlang density functions to analyze first-pass pulmonary uptake of multiple indicators in dogs. J Pharmacokinet Biopharm. 1996;24(6):569–88.

    Article  CAS  PubMed  Google Scholar 

  63. Wang WB, Watts AB, Peters JI, Williams RO III. The impact of pulmonary disease on the fate of inhaled medicines- a review. Int J Phram. 2014;461:112–28.

    Article  CAS  Google Scholar 

  64. Sweeney TD, Skornik WA, Brain JD, Hatch V, Godleski JJ. Chronic bronchitis alters the pattern of aerosol deposition in the lung. Am J Respir Crit Care Med. 1995;151:482–8.

    Article  CAS  PubMed  Google Scholar 

  65. Patton JS, Brain JD, Davies LA, et al. The particle has landed- characterizing the fate of inhaled pharmaceuticals. J Aerosol Med Pulm Drug Deliv. 2010;23(Suppl 2):S71–87.

    Article  CAS  PubMed  Google Scholar 

  66. Patton JS, Fishburn CS, Weers JG. The lungs as a portal of entry for systemic drug delivery. Proc Am Thorac Soc. 2004;1:338–44.

    Article  CAS  PubMed  Google Scholar 

  67. Olsson B, Bodesson E, Borgstom L. Pulmonary drug metabolism, clearance, and absorption. In: Smyth HDC, Hickey AJ, editors. Controlled pulmonary drug delivery. 1st ed. New York: Springer; 2011.

    Google Scholar 

  68. Ryan JW. Processing of endogenous polypeptides by the lungs. Annu Rev Physiol. 1982;44:241–55.

    Article  CAS  PubMed  Google Scholar 

  69. Orfanos SE, Langleben D, Khoury J, et al. Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in humans. Circulation. 1999;99(12):1593–9.

    Article  CAS  PubMed  Google Scholar 

  70. Skidgel RA. Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. J Cardiovasc Pharmacol. 1992;20(Suppl 9):S4–9.

    Article  CAS  PubMed  Google Scholar 

  71. Chand N, Altura BM. Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: role in lung vascular diseases. Science. 1981;213(4514):1376–9.

    Article  CAS  PubMed  Google Scholar 

  72. Skidgel RA, Erdos EG. Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Peptides. 2004;25(3):521–5.

    Article  CAS  PubMed  Google Scholar 

  73. Simke J, Graeme ML, Sigg EB. Bradykinin induced bronchoconstriction in guinea pigs and its modification by various agents. Arch Int Pharmacodyn Ther. 1967;165(2):291–301.

    CAS  PubMed  Google Scholar 

  74. Collier HO. Humoral factors in bronchoconstriction. Sci Basis Med Annu Rev. 1968:308–35.

    Google Scholar 

  75. Suguikawa TR, Garcia CA, Martinez EZ, Vianna EO. Cough and dyspnea during bronchoconstriction: comparison of different stimuli. Cough. 2009;5:6.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Enseleit F, Hurlimann D, Luscher TF. Vascular protective effects of angiotensin converting enzyme inhibitors and their relation to clinical events. J Cardiovasc Pharmacol. 2001;37(Suppl 1):S21–30.

    Article  CAS  PubMed  Google Scholar 

  77. Muntner P, Krousel-Wood M, Hyre AD, et al. Antihypertensive prescriptions for newly treated patients before and after the main antihypertensive and lipid-lowering treatment to prevent heart attack trial results and seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure guidelines [see comment]. Hypertension. 2009;53(4):617–23.

    Article  CAS  PubMed  Google Scholar 

  78. Alabaster VA, Bakhle YS. Removal of 5-hydroxytryptamine in the pulmonary circulation of rat isolated lungs. Br J Pharmacol. 1970;40(3):468–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gonmori K, Rao KS, Mehendale HM. Pulmonary synthesis of 5-hydroxytryptamine in isolated perfused rabbit and rat lung preparations. Exp Lung Res. 1986;11(4):295–305.

    Article  CAS  PubMed  Google Scholar 

  80. Cook DR, Brandom BW. Enflurane, halothane, and isoflurane inhibit removal of 5-hydroxytryptamine from the pulmonary circulation. Anesth Analg. 1982;61(8):671–5.

    CAS  PubMed  Google Scholar 

  81. Junod AF. Uptake, metabolism and efflux of 14 C-5-hydroxytryptamine in isolated perfused rat lungs. J Pharmacol Exp Ther. 1972;183(2):341–55.

    CAS  PubMed  Google Scholar 

  82. Righi L, Volante M, Rapa I, Scagliotti GV, Papotti M. Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data. Virchows Arch. 2007;451(Suppl 1):S51–9.

    Article  PubMed  Google Scholar 

  83. Shah PM, Raney AA. Tricuspid valve disease. Curr Probl Cardiol. 2008;33(2):47–84.

    Article  PubMed  Google Scholar 

  84. Sandmann H, Pakkal M, Steeds R. Cardiovascular magnetic resonance imaging in the assessment of carcinoid heart disease. Clin Radiol. 2009;64(8):761–6.

    Article  CAS  PubMed  Google Scholar 

  85. Bernheim AM, Connolly HM, Pellikka PA. Carcinoid heart disease. Curr Treat Options Cardiovasc Med. 2007;9(6):482–9.

    Article  PubMed  Google Scholar 

  86. Droogmans S, Cosyns B, D’Haenen H, et al. Possible association between 3, 4-methylenedioxymethamphetamine abuse and valvular heart disease. Am J Cardiol. 2007;100(9):1442–5.

    Article  CAS  PubMed  Google Scholar 

  87. Utsunomiya T, Krausz MM, Shepro D, Hechtman HB. Prostaglandin control of plasma and platelet 5-hydroxytryptamine in normal and embolized animals. Am J Phys. 1981;241(5):H766–71.

    CAS  Google Scholar 

  88. Stratmann G, Gregory GA. Neurogenic and humoral vasoconstriction in acute pulmonary thromboembolism [see comment]. Anesth Analg. 2003;97(2):341–54.

    Article  PubMed  Google Scholar 

  89. Huval WV, Mathieson MA, Stemp LI, et al. Therapeutic benefits of 5-hydroxytryptamine inhibition following pulmonary embolism. Ann Surg. 1983;197(2):220–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Said SI. Metabolic functions of the pulmonary circulation. Circ Res. 1982;50(3):325–33.

    Article  CAS  PubMed  Google Scholar 

  91. Philpot RM, Andersson TB, Eling TE. Uptake, accumulation, and metabolism of chemicals by the lung. In: Bakhle YS, Vane JR, editors. Metabolic functions of the lung. New York: Marcel Dekker; 1977. p. 123–71.

    Google Scholar 

  92. Garcia JG, Noonan TC, Jubiz W, Malik AB. Leukotrienes and the pulmonary microcirculation. Am Rev Respir Dis. 1987;136(1):161–9.

    Article  CAS  PubMed  Google Scholar 

  93. Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987;237(4819):1171–6.

    Article  CAS  PubMed  Google Scholar 

  94. Haeggstrom JZ, Kull F, Rudberg PC, Tholander F, Thunnissen MMGM. Leukotriene A4 hydrolase. Prostaglandins Other Lipid Mediat. 2002;68–69:495–510.

    Article  PubMed  Google Scholar 

  95. Yang G, Chen G, Wang D. Effects of prostaglandins and leukotrienes on hypoxic pulmonary vasoconstriction in rats. J Tongji Med Univ. 2000;20(3):197–9.

    Article  CAS  PubMed  Google Scholar 

  96. Caironi P, Ichinose F, Liu R, Jones RC, Bloch KD, Zapol WM. 5-lipoxygenase deficiency prevents respiratory failure during ventilator-induced lung injury [see comment]. Am J Respir Crit Care Med. 2005;172(3):334–43.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Leitch AG. The role of leukotrienes in asthma. Ann Acad Med Singap. 1985;14(3):503–7.

    CAS  PubMed  Google Scholar 

  98. Sprague RS, Stephenson AH, Dahms TE, Lonigro AJ. Proposed role for leukotrienes in the pathophysiology of multiple systems organ failure. Crit Care Clin. 1989;5(2):315–29.

    Article  CAS  PubMed  Google Scholar 

  99. Orfanos SE, Mavrommati I, Korovesi I, Roussos C. Pulmonary endothelium in acute lung injury: from basic science to the critically ill. Intensive Care Med. 2004;30(9):1702–14.

    Article  CAS  PubMed  Google Scholar 

  100. Huang SK, Peters-Golden M. Eicosanoid lipid mediators in fibrotic lung diseases: ready for prime time? Chest. 2008;133(6):1442–50.

    Article  CAS  PubMed  Google Scholar 

  101. Del Giudice MM, Pezzulo A, Capristo C, et al. Leukotriene modifiers in the treatment of asthma in children. Ther Adv Respir Dis. 2009;3(5):245–51.

    Article  PubMed  Google Scholar 

  102. O’Byrne PM, Gauvreau GM, Murphy DM. Efficacy of leukotriene receptor antagonists and synthesis inhibitors in asthma. J Allergy Clin Immunol. 2009;124(3):397–403.

    Article  PubMed  CAS  Google Scholar 

  103. Tantisira KG, Drazen JM. Genetics and pharmacogenetics of the leukotriene pathway. J Allergy Clin Immunol. 2009;124(3):422–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Murphy RC, Gijon MA. Biosynthesis and metabolism of leukotrienes [erratum appears in Biochem J. 2007 Sep 15;406(3):527]. Biochem J. 2007;405(3):379–95.

    Article  CAS  PubMed  Google Scholar 

  105. Romano M. Lipid mediators: lipoxin and aspirin-triggered 15-epi-lipoxins. Inflamm Allergy Drug Targets. 2006;5(2):81–90.

    Article  CAS  PubMed  Google Scholar 

  106. Romano M, Recchia I, Recchiuti A. Lipoxin receptors. Sci World J. 2007;7:1393–412.

    Article  CAS  Google Scholar 

  107. Soyombo O, Spur BW, Lee TH. Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet-activating factor and N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Allergy. 1994;49(4):230–4.

    Article  CAS  PubMed  Google Scholar 

  108. Raud J, Palmertz U, Dahlen SE, Hedqvist P. Lipoxins inhibit microvascular inflammatory actions of leukotriene B4. Adv Exp Med Biol. 1991;314:185–92.

    Article  CAS  PubMed  Google Scholar 

  109. Le Y, Li B, Gong W, et al. Novel pathophysiological role of classical chemotactic peptide receptors and their communications with chemokine receptors. Immunol Rev. 2000;177:185–94.

    Article  CAS  PubMed  Google Scholar 

  110. Colgan SP, Serhan CN, Parkos CA, Delp-Archer C, Madara JL. Lipoxin A4 modulates transmigration of human neutrophils across intestinal epithelial monolayers. J Clin Invest. 1993;92(1):75–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Brezinski ME, Gimbrone MA Jr, Nicolaou KC, Serhan CN. Lipoxins stimulate prostacyclin generation by human endothelial cells. FEBS Lett. 1989;245(1–2):167–72.

    Article  CAS  PubMed  Google Scholar 

  112. Wenzel SE, Busse WW, The National Heart, Lung, Blood Institute’s Severe Asthma Research Program. Severe asthma: lessons from the Severe Asthma Research Program. J Allergy Clin Immunol. 2007;119(1):14–21; quiz 22–13.

    Article  PubMed  Google Scholar 

  113. Vachier I, Bonnans C, Chavis C, et al. Severe asthma is associated with a loss of LX4, an endogenous anti-inflammatory compound. J Allergy Clin Immunol. 2005;115(1):55–60.

    Article  CAS  PubMed  Google Scholar 

  114. Levy BD, Bonnans C, Silverman ES, et al. Diminished lipoxin biosynthesis in severe asthma. Am J Respir Crit Care Med. 2005;172(7):824–30.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Kupczyk M, Antczak A, Kuprys-Lipinska I, Kuna P. Lipoxin A4 generation is decreased in aspirin-sensitive patients in lysine-aspirin nasal challenge in vivo model. Allergy. 2009;64(12):1746–52.

    Article  CAS  PubMed  Google Scholar 

  116. Van Hove CL, Maes T, Joos GF, Tournoy KG. Chronic inflammation in asthma: a contest of persistence vs. resolution. Allergy. 2008;63(9):1095–109.

    Article  PubMed  CAS  Google Scholar 

  117. Bonnans C, Levy BD. Lipid mediators as agonists for the resolution of acute lung inflammation and injury. Am J Respir Cell Mol Biol. 2007;36(2):201–5.

    Article  CAS  PubMed  Google Scholar 

  118. Serhan CN. Lipoxins and novel aspirin-triggered 15-epi-lipoxins (ATL): a jungle of cell-cell interactions or a therapeutic opportunity? Prostaglandins. 1997;53(2):107–37.

    Article  CAS  PubMed  Google Scholar 

  119. Ramalho TC, Rocha MVJ, da Cunha EFF, Freitas MP. The search for new COX-2 inhibitors: a review of 2002–2008 patents. Expert Opin Ther Pat. 2009;19(9):1193–228.

    Article  CAS  PubMed  Google Scholar 

  120. Grosser T. Variability in the response to cyclooxygenase inhibitors: toward the individualization of nonsteroidal anti-inflammatory drug therapy. J Investig Med. 2009;57(6):709–16.

    Article  CAS  PubMed  Google Scholar 

  121. Funk CD, FitzGerald GA. COX-2 inhibitors and cardiovascular risk. J Cardiovasc Pharmacol. 2007;50(5):470–9.

    Article  CAS  PubMed  Google Scholar 

  122. Frangos JA, Eskin SG, McIntire LV, Ives CL. Flow effects on prostacyclin production by cultured human endothelial cells. Science. 1985;227(4693):1477–9.

    Article  CAS  PubMed  Google Scholar 

  123. Eling TE, Ally AI. Pulmonary biosynthesis and metabolism of prostaglandins and related substances. Environ Health Perspect. 1984;55:159–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Robinson C, Hardy CC, Holgate ST. Pulmonary synthesis, release and metabolism of prostaglandins. J Allergy Clin Immunol. 1985;76(2 Pt 2):265–71.

    Article  CAS  PubMed  Google Scholar 

  125. McGiff JC, Terragno NA, Strand JC, Lee JB, Lonigro AJ, Ng KK. Selective passage of prostaglandins across the lung. Nature. 1969;223(5207):742–5.

    Article  CAS  PubMed  Google Scholar 

  126. Dusting GJ, Moncada S, Vane JR. Recirculation of prostacyclin (PGI2) in the dog. Br J Pharmacol. 1978;64(2):315–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Gardiner PJ. Eicosanoids and airway smooth muscle. Pharmacol Ther. 1989;44(1):1–62.

    Article  CAS  PubMed  Google Scholar 

  128. Regner KR, Connolly HM, Schaff HV, Albright RC. Acute renal failure after cardiac surgery for carcinoid heart disease: incidence, risk factors, and prognosis. Am J Kidney Dis. 2005;45(5):826–32.

    Article  PubMed  Google Scholar 

  129. Zeldin DC, Foley J, Ma J, et al. CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. Mol Pharmacol. 1996;50(5):1111–7.

    CAS  PubMed  Google Scholar 

  130. Salvail D, Dumoulin M, Rousseau E. Direct modulation of tracheal cl – channel activity by 5, 6- and 11, 12-EET. Am J Phys. 1998;275(3 Pt 1):L432–41.

    CAS  Google Scholar 

  131. Birks EK, Bousamra M, Presberg K, Marsh JA, Effros RM, Jacobs ER. Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue. Am J Phys. 1997;272(5 Pt 1):L823–9.

    CAS  Google Scholar 

  132. Jacobs ER, Zeldin DC. The lung HETEs (and EETs) up. Am J Physiol Heart Circ Physiol. 2001;280(1):H1–10.

    Article  CAS  PubMed  Google Scholar 

  133. Sirois P, Gutkowska J. Atrial natriuretic factor immunoreactivity in human fetal lung tissue and perfusates. Hypertension. 1988;11(2 Pt 2):I62–5.

    CAS  PubMed  Google Scholar 

  134. Di Nardo P, Peruzzi G. Physiology and pathophysiology of atrial natriuretic factor in lungs. Can J Cardiol. 1992;8(5):503–8.

    PubMed  Google Scholar 

  135. Turrin M, Gillis CN. Removal of atrial natriuretic peptide by perfused rabbit lungs in situ. Biochem Biophys Res Commun. 1986;140(3):868–73.

    Article  CAS  PubMed  Google Scholar 

  136. Tomlinson JW, Walker EA, Bujalska IJ, et al. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev. 2004;25(5):831–66.

    Article  CAS  PubMed  Google Scholar 

  137. Garbrecht MR, Klein JM, Schmidt TJ, Snyder JM. Glucocorticoid metabolism in the human fetal lung: implications for lung development and the pulmonary surfactant system. Biol Neonate. 2006;89(2):109–19.

    Article  CAS  PubMed  Google Scholar 

  138. Baker RW, Walker BR, Shaw RJ, et al. Increased cortisol: cortisone ratio in acute pulmonary tuberculosis. Am J Respir Crit Care Med. 2000;162(5):1641–7.

    Article  CAS  PubMed  Google Scholar 

  139. Huang CH, Huang HH, Chen TL, Wang MJ. Perioperative changes of plasma endothelin-1 concentrations in patients undergoing cardiac valve surgery. Anaesth Intensive Care. 1996;24(3):342–7.

    CAS  PubMed  Google Scholar 

  140. Dupuis J, Cernacek P, Tardif JC, et al. Reduced pulmonary clearance of endothelin-1 in pulmonary hypertension. Am Heart J. 1998;135(4):614–20.

    Article  CAS  PubMed  Google Scholar 

  141. Drinker CK, Churchill ED, Ferry RM. The volume of blood in the heart and lungs. Am J Phys. 1926;77(3):590–622.

    Article  CAS  Google Scholar 

  142. Campbell I, Waterhouse J. Fluid balance and non-respiratory functions of the lung. Anaesth Intensive Care Med. 2005;6(11):370–1.

    Article  Google Scholar 

  143. Cotter G, Metra M, Milo-Cotter O, Dittrich HC, Gheorghiade M. Fluid overload in acute heart failure – re-distribution and other mechanisms beyond fluid accumulation. Eur J Heart Fail. 2008;10(2):165–9.

    Article  PubMed  Google Scholar 

  144. Jules-Elysee K, Blanck TJJ, Catravas JD, et al. Angiotensin-converting enzyme activity: a novel way of assessing pulmonary changes during total knee arthroplasty. Anesth Analg. 2004;99(4):1018–23.

    Article  PubMed  Google Scholar 

  145. Lovering AT, Stickland MK, Kelso AJ, Eldridge MW. Direct demonstration of 25- and 50-microm arteriovenous pathways in healthy human and baboon lungs. Am J Physiol Heart Circ Physiol. 2007;292(4):H1777–81.

    Article  CAS  PubMed  Google Scholar 

  146. Lovering AT, Haverkamp HC, Romer LM, Hokanson JS, Eldridge MW. Transpulmonary passage of 99mTc macroaggregated albumin in healthy humans at rest and during maximal exercise. J Appl Physiol. 2009;106(6):1986–92.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Abrams GA, Rose K, Fallon MB, et al. Hepatopulmonary syndrome and venous emboli causing intracerebral hemorrhages after liver transplantation: a case report. Transplantation. 1999;68(11):1809–11.

    Article  CAS  PubMed  Google Scholar 

  148. Colohan AR, Perkins NA, Bedford RF, Jane JA. Intravenous fluid loading as prophylaxis for paradoxical air embolism. J Neurosurg. 1985;62(6):839–42.

    Article  CAS  PubMed  Google Scholar 

  149. Breeze RG, Wheeldon EB. The cells of the pulmonary airways. Am Rev Respir Dis. 1977;116(4):705–77.

    Article  CAS  PubMed  Google Scholar 

  150. Rogers DF. The airway goblet cell. Int J Biochem Cell Biol. 2003;35(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  151. Huffmyer JL, Littlewood KE, Nemergut EC. Perioperative management of the adult with cystic fibrosis. Anesth Analg. 2009;109(6):1949–61.

    Article  PubMed  Google Scholar 

  152. Nadel JA. Neural control of airway submucosal gland secretion. Eur J Respir Dis Suppl. 1983;128(Pt 1):322–6.

    PubMed  Google Scholar 

  153. Reid L. Measurement of the bronchial mucous gland layer: a diagnostic yardstick in chronic bronchitis. Thorax. 1960;15:132–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Gallagher JT, Kent PW, Passatore M, Phipps RJ, Richardson PS. The composition of tracheal mucus and the nervous control of its secretion in the cat. Proc R Soc Lond B Biol Sci. 1975;192(1106):49–76.

    Article  CAS  PubMed  Google Scholar 

  155. Heidsiek JG, Hyde DM, Plopper CG, St George JA. Quantitative histochemistry of mucosubstance in tracheal epithelium of the macaque monkey. J Histochem Cytochem. 1987;35(4):435–42.

    Article  CAS  PubMed  Google Scholar 

  156. Evans CM, Williams OW, Tuvim MJ, et al. Mucin is produced by clara cells in the proximal airways of antigen-challenged mice. Am J Respir Cell Mol Biol. 2004;31(4):382–94.

    Article  CAS  PubMed  Google Scholar 

  157. Reynolds SD, Malkinson AM. Clara cell: progenitor for the bronchiolar epithelium. Int J Biochem Cell Biol. 2009;42(1):1–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  158. Boers JE, Ambergen AW, Thunnissen FB. Number and proliferation of clara cells in normal human airway epithelium. Am J Respir Crit Care Med. 1999;159(5 Pt 1):1585–91.

    Article  CAS  PubMed  Google Scholar 

  159. Krishnaswamy G, Ajitawi O, Chi DS. The human mast cell: an overview. Methods Mol Biol. 2006;315:13–34.

    PubMed  Google Scholar 

  160. Taube C, Stassen M. Mast cells and mast cell-derived factors in the regulation of allergic sensitization. Chem Immunol Allergy. 2008;94:58–66.

    Article  CAS  PubMed  Google Scholar 

  161. Peters A, Veronesi B, Calderon-Garciduenas L, et al. Translocation and potential neurological effects of fine and ultrafine particles a critical update. Part Fibre Toxicol [Electronic Resource]. 2006;3:13.

    Article  CAS  Google Scholar 

  162. Jakubzick C, Tacke F, Llodra J, van Rooijen N, Randolph GJ. Modulation of dendritic cell trafficking to and from the airways. J Immunol. 2006;176(6):3578–84.

    Article  CAS  PubMed  Google Scholar 

  163. Matthay MA, Folkesson HG, Clerici C. Lung epithelial fluid transport and the resolution of pulmonary edema. Physiol Rev. 2002;82(3):569–600.

    Article  CAS  PubMed  Google Scholar 

  164. Matthay MA, Clerici C, Saumon G. Invited review: active fluid clearance from the distal air spaces of the lung. J Appl Physiol. 2002;93(4):1533–41.

    Article  CAS  PubMed  Google Scholar 

  165. Dobbs LG, Johnson MD. Alveolar epithelial transport in the adult lung. Respir Physiol Neurobiol. 2007;159:283–300.

    Article  CAS  PubMed  Google Scholar 

  166. Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. Regulation of surfactant secretion in alveolar type II cells. Am J Physiol Lung Cell Mol Physiol. 2007;293(2):L259–71.

    Article  CAS  PubMed  Google Scholar 

  167. Weaver TE, Conkright JJ. Function of surfactant proteins B and C. Annu Rev Physiol. 2001;63:555–78.

    Article  CAS  PubMed  Google Scholar 

  168. Ungaro F, d’Angelo I, Miro A, La Rotonda MI, Quaglia F. Engineered PLGA nano- and micro-carriers for pulmonary delivery: challenges and promises. J Pharm Pharmacol. 2012;64:1217–35.

    Article  CAS  PubMed  Google Scholar 

  169. Wanner A, Salathe M, O’Riordan TG. Mucociliary clearance in the airways. Am J Respir Crit Care Med. 1996;154(6 Pt 1):1868–902.

    Article  CAS  PubMed  Google Scholar 

  170. Boucher RC. Evidence for airway surface dehydration as the initiating event in CF airway disease. J Intern Med. 2007;261(1):5–16.

    Article  CAS  PubMed  Google Scholar 

  171. McFadden ER Jr. Heat and water exchange in human airways. Am Rev Respir Dis. 1992;146(5 Pt 2):S8–10.

    Article  PubMed  Google Scholar 

  172. Crouch E, Wright JR. Surfactant proteins a and d and pulmonary host defense. Annu Rev Physiol. 2001;63:521–54.

    Article  CAS  PubMed  Google Scholar 

  173. Wu H, Kuzmenko A, Wan S, et al. Surfactant proteins a and D inhibit the growth of gram-negative bacteria by increasing membrane permeability [see comment]. J Clin Invest. 2003;111(10):1589–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Wright JR. Pulmonary surfactant: a front line of lung host defense [comment]. J Clin Invest. 2003;111(10):1453–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Hamann KJ, Dorscheid DR, Ko FD, et al. Expression of Fas (CD95) and FasL (CD95L) in human airway epithelium. Am J Respir Cell Mol Biol. 1998;19:537–42.

    Article  CAS  PubMed  Google Scholar 

  176. Fine A, Anderson NL, Rothstein TL, Williams MC, Gochuico BR. Fas expression in pulmonary alveolar type II cells. Am J Phys. 1997;273:L64_L71.

    Google Scholar 

  177. Muzio M, Salvesen GS, Dixit VM. FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens. J Biol Chem. 1997;272:2952–6.

    Article  CAS  PubMed  Google Scholar 

  178. Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270:1189–92.

    Article  CAS  PubMed  Google Scholar 

  179. Wadsworth SJ, Atsuta R, McIntyre JO, Hackett TL, Singhera GK, Dorscheid DR. IL-13 and T(H)2 cytokine exposure triggers matrix metalloproteinase 7-mediated Fas ligand cleavage from bronchial epithelial cells. J Allergy Clin Immunol. 2011;126(2):366–74, 374 e1–8.

    Article  CAS  Google Scholar 

  180. Kaisho T, Akira S. Toll-like receptor function and signaling. J Allergy Clin Immunol. 2006;117:979–87.

    Article  CAS  PubMed  Google Scholar 

  181. Bals R, Hiemstra PS. Innate immunity in the lung: how epithelial cells fight against respiratory pathogens. Eur Respir J. 2004;23:327–33.

    Article  CAS  PubMed  Google Scholar 

  182. Mio T, Romberger DJ, Thompson AB, Robbins RA, Heires A, Rennard SI. Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. Am J Respir Crit Care Med. 1997;155:1770–6.

    Article  CAS  PubMed  Google Scholar 

  183. Chung KF. Cytokines in chronic obstructive pulmonary disease. Eur Respir J. 2001;34(Suppl):50s–9s.

    Article  CAS  Google Scholar 

  184. Russo RG, Liotta LA, Thorgeirsson U, Brundage R, Schiffmann E. Polymorphonuclear leukocyte migration through human amnion membrane. J Cell Biol. 1981;91:459–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  185. Kao YJ, Piedra PA, Larsen GL, Colasurdo GN. Induction and regulation of nitric oxide synthase in airway epithelial cells by respiratory syncytial virus. Am J Respir Crit Care Med. 2001;163:532–9.

    Article  CAS  PubMed  Google Scholar 

  186. Zheng S, De SBP, Choudhary S, et al. Impaired innate host defense causes susceptibility to respiratory virus infections in cystic fibrosis. Immunity. 2003;18:619–30.

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, USA

    Amanda M. Kleiman & Keith E. Littlewood

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    Peter Slinger

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Kleiman, A.M., Littlewood, K.E. (2019). Nonrespiratory Functions of the Lung. In: Slinger, P. (eds) Principles and Practice of Anesthesia for Thoracic Surgery. Springer, Cham. https://doi.org/10.1007/978-3-030-00859-8_7

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