Log in | Register

Hypercapnic acidosis transiently weakens hypoxic pulmonary vasoconstriction without affecting endogenous pulmonary nitric oxide production

Manja C. A. Nilsson| Filip Fredén| Anders Larsson| Peter Wiklund| Maria Bergquist| Kristina Hambraeus-Jonzon
Experimental
Volume 38, Issue 3 / March , 2012

Pages 509 - 517

Abstract

Purpose

Hypercapnic acidosis often occurs in critically ill patients and during protective mechanical ventilation; however, the effect of hypercapnic acidosis on endogenous nitric oxide (NO) production and hypoxic pulmonary vasoconstriction (HPV) presents conflicting results. The aim of this study is to test the hypothesis that hypercapnic acidosis augments HPV without changing endogenous NO production in both hyperoxic and hypoxic lung regions in pigs.

Methods

Sixteen healthy anesthetized pigs were separately ventilated with hypoxic gas to the left lower lobe (LLL) and hyperoxic gas to the rest of the lung. Eight pigs received 10% carbon dioxide (CO2) inhalation to both lung regions (hypercapnia group), and eight pigs formed the control group. NO concentration in exhaled air (ENO), nitric oxide synthase (NOS) activity, cyclic guanosine monophosphate (cGMP) in lung tissue, and regional pulmonary blood flow were measured.

Results

There were no differences between the groups for ENO, Ca2+-independent or Ca2+-dependent NOS activity, or cGMP in hypoxic or hyperoxic lung regions. Relative perfusion to LLL (QLLL/QT) was reduced similarly in both groups when LLL hypoxia was induced. During the first 90 min of hypercapnia, QLLL/QT increased from 6% (1%) [mean (standard deviation, SD)] to 9% (2%) (p < 0.01), and then decreased to the same level as the control group, where QLLL/QT remained unchanged. Cardiac output increased during hypercapnia (p < 0.01), resulting in increased oxygen delivery (p < 0.01), despite decreased PaO2 (p < 0.01).

Conclusions

Hypercapnic acidosis does not potentiate HPV, but rather transiently weakens HPV, and does not affect endogenous NO production in either hypoxic or hyperoxic lung regions.

Keywords

References

  1. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR (1998) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 338:347–354
    • View reference on PubMed
    • View reference on publisher's website
  2. Feihl F, Perret C (1994) Permissive hypercapnia. How permissive should we be? Am J Respir Crit Care Med 150:1722–1737
    • View reference on PubMed
  3. Gordon JB, Rehorst-Paea LA, Hoffman GM, Nelin LD (1999) Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets. Pediatr Res 46:735–741
    • View reference on PubMed
    • View reference on publisher's website
  4. Chang AC, Zucker HA, Hickey PR, Wessel DL (1995) Pulmonary vascular resistance in infants after cardiac surgery: role of carbon dioxide and hydrogen ion. Crit Care Med 23:568–574
    • View reference on PubMed
    • View reference on publisher's website
  5. Brimioulle S, Lejeune P, Vachiery JL, Leeman M, Melot C, Naeije R (1990) Effects of acidosis and alkalosis on hypoxic pulmonary vasoconstriction in dogs. Am J Physiol 258:H347–H353
    • View reference on PubMed
  6. Balasubramanyan N, Halla TR, Ghanayem NS, Gordon JB (2000) Endothelium-independent and -dependent vasodilation in alkalotic and acidotic piglet lungs. Pediatr Pulmonol 30:241–248
    • View reference on PubMed
    • View reference on publisher's website
  7. Ketabchi F, Egemnazarov B, Schermuly RT, Ghofrani HA, Seeger W, Grimminger F, Shid-Moosavi M, Dehghani GA, Weissmann N, Sommer N (2009) Effects of hypercapnia with and without acidosis on hypoxic pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 297:L977–L983
    • View reference on PubMed
    • View reference on publisher's website
  8. Carr P, Graves JE, Poston L (1993) Carbon dioxide induced vasorelaxation in rat mesenteric small arteries precontracted with noradrenaline is endothelium dependent and mediated by nitric oxide. Pflugers Arch 423:343–345
    • View reference on PubMed
    • View reference on publisher's website
  9. Najarian T, Marrache AM, Dumont I, Hardy P, Beauchamp MH, Hou X, Peri K, Gobeil F Jr, Varma DR, Chemtob S (2000) Prolonged hypercapnia-evoked cerebral hyperemia via K(+) channel- and prostaglandin E(2)-dependent endothelial nitric oxide synthase induction. Circ Res 87:1149–1156
    • View reference on PubMed
  10. Archer SL, Tolins JP, Raij L, Weir EK (1989) Hypoxic pulmonary vasoconstriction is enhanced by inhibition of the synthesis of an endothelium derived relaxing factor. Biochem Biophys Res Commun 164:1198–1205
    • View reference on PubMed
    • View reference on publisher's website
  11. Freden F, Wei SZ, Berglund JE, Frostell C, Hedenstierna G (1995) Nitric oxide modulation of pulmonary blood flow distribution in lobar hypoxia. Anesthesiology 82:1216–1225
    • View reference on PubMed
    • View reference on publisher's website
  12. Naeije R, Brimioulle S (2001) Physiology in medicine: importance of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation during acute respiratory failure. Crit Care 5:67–71
    • View reference on PubMed
    • View reference on publisher's website
  13. Nilsson MC, Freden F, Wiklund P, Hambraeus-Jonzon K (2011) No effect of metabolic acidosis on nitric oxide production in hypoxic and hyperoxic lung regions in pigs. Acta Physiol (Oxf) 202:59–68
    • View reference on publisher's website
  14. Carlin RE, Ferrario L, Boyd JT, Camporesi EM, McGraw DJ, Hakim TS (1997) Determinants of nitric oxide in exhaled gas in the isolated rabbit lung. Am J Respir Crit Care Med 155:922–927
    • View reference on PubMed
  15. Uematsu M, Ohara Y, Navas JP, Nishida K, Murphy TJ, Alexander RW, Nerem RM, Harrison DG (1995) Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress. Am J Physiol 269:C1371–C1378
    • View reference on PubMed
  16. Warren JB, Maltby NH, MacCormack D, Barnes PJ (1989) Pulmonary endothelium-derived relaxing factor is impaired in hypoxia. Clin Sci (Lond) 77:671–676
  17. Kantrow SP, Huang YC, Whorton AR, Grayck EN, Knight JM, Millington DS, Piantadosi CA (1997) Hypoxia inhibits nitric oxide synthesis in isolated rabbit lung. Am J Physiol 272:L1167–L1173
    • View reference on PubMed
  18. Hambraeus-Jonzon K, Chen L, Freden F, Wiklund P, Hedenstierna G (2001) Pulmonary vasoconstriction during regional nitric oxide inhalation: evidence of a blood-borne regulator of nitric oxide synthase activity. Anesthesiology 95:102–112
    • View reference on PubMed
    • View reference on publisher's website
  19. Hampl V, Cornfield DN, Cowan NJ, Archer SL (1995) Hypoxia potentiates nitric oxide synthesis and transiently increases cytosolic calcium levels in pulmonary artery endothelial cells. Eur Respir J 8:515–522
    • View reference on PubMed
  20. Hampl V (1997) The role of endogenous nitric oxide in acute hypoxic pulmonary vasoconstriction. In: Nitric oxide and the lung, Marcel Dekker Inc, pp 113–127
  21. Frasch HF, Marshall C, Marshall BE (1999) Endothelin-1 is elevated in monocrotaline pulmonary hypertension. Am J Physiol 276:L304–L310
    • View reference on PubMed
  22. Rimeika D, Wiklund NP, Lindahl SG, Wiklund CU (2006) Regional differences in nitric oxide-mediated vasorelaxation in porcine pulmonary arteries. Acta Anaesthesiol Scand 50:947–953
    • View reference on PubMed
    • View reference on publisher's website
  23. Fujii Y, Goldberg P, Hussain SN (1998) Intrathoracic and extrathoracic sources of exhaled nitric oxide in porcine endotoxemic shock. Chest 114:569–576
    • View reference on PubMed
    • View reference on publisher's website
  24. Mizuno S, Demura Y, Ameshima S, Okamura S, Miyamori I, Ishizaki T (2002) Alkalosis stimulates endothelial nitric oxide synthase in cultured human pulmonary arterial endothelial cells. Am J Physiol Lung Cell Mol Physiol 283:L113–L119
    • View reference on PubMed
  25. Huang CJ, Haque IU, Slovin PN, Nielsen RB, Fang X, Skimming JW (2002) Environmental pH regulates LPS-induced nitric oxide formation in murine macrophages. Nitric Oxide 6:73–78
    • View reference on PubMed
    • View reference on publisher's website
  26. Walley KR, Lewis TH, Wood LD (1990) Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs. Circ Res 67:628–635
    • View reference on PubMed
  27. Brofman JD, Leff AR, Munoz NM, Kirchhoff C, White SR (1990) Sympathetic secretory response to hypercapnic acidosis in swine. J Appl Physiol 69:710–717
    • View reference on PubMed
  28. Nakahata K, Kinoshita H, Hirano Y, Kimoto Y, Iranami H, Hatano Y (2003) Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K + channels in parenchymal microvessels of the rat cerebral cortex. Anesthesiology 99:1333–1339
    • View reference on PubMed
    • View reference on publisher's website
  29. Sandoval J, Long GR, Skoog C, Wood LD, Oppenheimer L (1983) Independent influence of blood flow rate and mixed venous PO2 on shunt fraction. J Appl Physiol 55:1128–1133
    • View reference on PubMed
  30. Domino KB, Wetstein L, Glasser SA, Lindgren L, Marshall C, Harken A, Marshall BE (1983) Influence of mixed venous oxygen tension (PVO2) on blood flow to atelectatic lung. Anesthesiology 59:428–434
    • View reference on PubMed
    • View reference on publisher's website
  31. Benumof JL, Wahrenbrock EA (1975) Blunted hypoxic pulmonary vasoconstriction by increased lung vascular pressures. J Appl Physiol 38:846–850
    • View reference on PubMed
  32. Cheney FW, Colley PS (1980) The effect of cardiac output on arterial blood oxygenation. Anesthesiology 52:496–503
    • View reference on PubMed
    • View reference on publisher's website
  33. Wang Z, Su F, Bruhn A, Yang X, Vincent JL (2008) Acute hypercapnia improves indices of tissue oxygenation more than dobutamine in septic shock. Am J Respir Crit Care Med 177:178–183
    • View reference on PubMed
    • View reference on publisher's website
  34. Berger MG, Vandier C, Bonnet P, Jackson WF, Rusch NJ (1998) Intracellular acidosis differentially regulates KV channels in coronary and pulmonary vascular muscle. Am J Physiol 275:H1351–H1359
    • View reference on PubMed
  35. Viles PH, Shepherd JT (1968) Evidence for a dilator action of carbon dioxide on the pulmonary vessels of the cat. Circ Res 22:325–332
    • View reference on PubMed
  36. Baudouin SV, Evans TW (1993) Action of carbon dioxide on hypoxic pulmonary vasoconstriction in the rat lung: evidence against specific endothelium-derived relaxing factor-mediated vasodilation. Crit Care Med 21:740–746
    • View reference on PubMed
    • View reference on publisher's website
  37. Chuang IC, Dong HP, Yang RC, Wang TH, Tsai JH, Yang PH, Huang MS (2010) Effect of carbon dioxide on pulmonary vascular tone at various pulmonary arterial pressure levels induced by endothelin-1. Lung 188:199–207
    • View reference on PubMed
    • View reference on publisher's website
  38. Geers CGG, Heming TA, Bidani A, Crandall ED (1986) Effects of intra-and extracellular carbonic anhydrase on CO2 excretion and intravascular pH equilibrium in the isolated perfused rat lung. Prog Respir Res 21:26–29
  39. Balanos GM, Talbot NP, Dorrington KL, Robbins PA (2003) Human pulmonary vascular response to 4 h of hypercapnia and hypocapnia measured using Doppler echocardiography. J Appl Physiol 94:1543–1551
    • View reference on PubMed
  40. Barer GR, Howard P, Shaw JW (1970) Sensitivity of pulmonary vessels to hypoxia and hypercapnia. J Physiol 206:25P–26P
    • View reference on PubMed
  41. Sibbald WJ, Paterson NA, Holliday RL, Anderson RA, Lobb TR, Duff JH (1978) Pulmonary hypertension in sepsis: measurement by the pulmonary arterial diastolic-pulmonary wedge pressure gradient and the influence of passive and active factors. Chest 73:583–591
    • View reference on PubMed
    • View reference on publisher's website

Sign In

Connect with ICM

Top 5 Articles Editors Picks Supplement