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. 1981 Oct;68(4):853–862. doi: 10.1172/JCI110340

Effects of inhibition of RBC HCO3-/Cl- exchange on CO2 excretion and downstream pH disequilibrium in isolated rat lungs.

E D Crandall, S J Mathew, R S Fleischer, H I Winter, A Bidani
PMCID: PMC370872  PMID: 6793631

Abstract

To determine the effects of the speed of the erythrocyte membrane chloride shift on pulmonary gas transfer, CO2 exchange and the kinetics of pH equilibration were measured with isolated rat lungs perfused with 20% suspensions of human erythrocytes. The lungs were ventilated with room air, and the inflowing perfusate blood gases were similar to those in mixed venous blood in vivo. All experiments were performed at 37 degrees C. Rates of CO2 excretion were determined by measuring the fraction of CO2 in mixed expired gas in a steady state. The time-course of extracellular pH equilibration in the effluent perfusate was measured in a downstream stopflow pH electrode apparatus. CO2 excretion was reduced by approximately 16% when the lungs were perfused with suspensions containing erythrocytes whose HCO-3/Cl- exchange rates was inhibited, compared with CO2 excretion when the lungs were perfused with normal erythrocyte suspensions. A fall of 0.06 in effluent perfusate extracellular pH was noted during perfusion with inhibited erythrocyte suspensions, in contrast to no observable downstream pH change during perfusion with normal erythrocyte suspensions. These results are in close agreement with the predictions of a theoretical model. Our observations suggest that CO2 transfer in capillary beds will be adversely affected in vivo when the rate of the erythrocyte HCO-3/Cl- exchange is abnormally low. Since a number of commonly used drugs are known to inhibit the chloride shift in human erythrocytes, these findings may have important clinical implications, especially in patients with impaired lung function.

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Selected References

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  1. Anderson C. J., Kaufman P. L., Sturm R. J. Toxicity of combined therapy with carbonic anhydrase inhibitors and aspirin. Am J Ophthalmol. 1978 Oct;86(4):516–519. doi: 10.1016/0002-9394(78)90299-4. [DOI] [PubMed] [Google Scholar]
  2. Bidani A., Crandall E. D. Slow postcapillary changes in blood pH in vivo: titration with acetazolamide. J Appl Physiol Respir Environ Exerc Physiol. 1978 Oct;45(4):565–573. doi: 10.1152/jappl.1978.45.4.565. [DOI] [PubMed] [Google Scholar]
  3. Brazy P. C., Gunn R. B. Furosemide inhibition of chloride transport in human red blood cells. J Gen Physiol. 1976 Dec;68(6):583–599. doi: 10.1085/jgp.68.6.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cabantchik Z. I., Rothstein A. Membrane proteins related to anion permeability of human red blood cells. I. Localization of disulfonic stilbene binding sites in proteins involved in permeation. J Membr Biol. 1974;15(3):207–226. doi: 10.1007/BF01870088. [DOI] [PubMed] [Google Scholar]
  5. Cabantchik Z. I., Rothstein A. The nature of the membrane sites controlling anion permeability of human red blood cells as determined by studies with disulfonic stilbene derivatives. J Membr Biol. 1972 Dec 29;10(3):311–330. doi: 10.1007/BF01867863. [DOI] [PubMed] [Google Scholar]
  6. Crandall E. D., Bidani A. Effects of red blood cell HCO3(-)/Cl- exchange kinetics on lung CO2 transfer: theory. J Appl Physiol Respir Environ Exerc Physiol. 1981 Feb;50(2):265–271. doi: 10.1152/jappl.1981.50.2.265. [DOI] [PubMed] [Google Scholar]
  7. Crandall E. D., Bidani A., Forster R. E. Postcapillary changes in blood pH in vivo during carbonic anhydrase inhibition. J Appl Physiol Respir Environ Exerc Physiol. 1977 Oct;43(4):582–590. doi: 10.1152/jappl.1977.43.4.582. [DOI] [PubMed] [Google Scholar]
  8. Crandall E. D., Klocke R. A., Forster R. E. Hydroxyl ion movements across the human erythrocyte membrane. Measurement of rapid pH changes in red cell suspensions. J Gen Physiol. 1971 Jun;57(6):664–683. doi: 10.1085/jgp.57.6.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crandall E. D., O'Brasky J. E. Direct evidence of participation of rat lung carbonic anhydrase in CO2 reactions. J Clin Invest. 1978 Sep;62(3):618–622. doi: 10.1172/JCI109168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Effros R. M., Chang R. S., Silverman P. Acceleration of plasma bicarbonate conversion to carbon dioxide by pulmonary carbonic anhydrase. Science. 1978 Jan 27;199(4327):427–429. doi: 10.1126/science.413195. [DOI] [PubMed] [Google Scholar]
  11. Effros R. M., Shapiro L., Silverman P. Carbonic anhydrase activity of rabbit lungs. J Appl Physiol Respir Environ Exerc Physiol. 1980 Oct;49(4):589–600. doi: 10.1152/jappl.1980.49.4.589. [DOI] [PubMed] [Google Scholar]
  12. Effros R. M., Weissman M. L. Carbonic anhydrase activity of the cat hind leg. J Appl Physiol Respir Environ Exerc Physiol. 1979 Nov;47(5):1090–1098. doi: 10.1152/jappl.1979.47.5.1090. [DOI] [PubMed] [Google Scholar]
  13. Gunn R. B., Dalmark M., Tosteson D. C., Wieth J. O. Characteristics of chloride transport in human red blood cells. J Gen Physiol. 1973 Feb;61(2):185–206. doi: 10.1085/jgp.61.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jacobs M. H., Stewart D. R. THE ROLE OF CARBONIC ANHYDRASE IN CERTAIN IONIC EXCHANGES INVOLVING THE ERYTHROCYTE. J Gen Physiol. 1942 Mar 20;25(4):539–552. doi: 10.1085/jgp.25.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klocke R. A. Catalysis of CO2 reactions by lung carbonic anhydrase. J Appl Physiol Respir Environ Exerc Physiol. 1978 Jun;44(6):882–888. doi: 10.1152/jappl.1978.44.6.882. [DOI] [PubMed] [Google Scholar]
  16. Klocke R. A. Equilibrium of CO2 reactions in the pulmonary capillary. J Appl Physiol Respir Environ Exerc Physiol. 1980 Jun;48(6):972–976. doi: 10.1152/jappl.1980.48.6.972. [DOI] [PubMed] [Google Scholar]
  17. Klocke R. A. Rate of bicarbonate-chloride exchange in human red cells at 37 degrees C. J Appl Physiol. 1976 May;40(5):707–714. doi: 10.1152/jappl.1976.40.5.707. [DOI] [PubMed] [Google Scholar]
  18. MADDY A. H. A FLUORESCENT LABEL FOR THE OUTER COMPONENTS OF THE PLASMA MEMBRANE. Biochim Biophys Acta. 1964 Sep 25;88:390–399. doi: 10.1016/0926-6577(64)90194-9. [DOI] [PubMed] [Google Scholar]
  19. Motais R., Baroin A., Motais A., Baldy S. Inhibition of anion and glucose permeabilities by anesthetics in erythrocytes. The mechanisms of action of positively and negatively charged drugs. Biochim Biophys Acta. 1980 Jul;599(2):673–688. doi: 10.1016/0005-2736(80)90209-6. [DOI] [PubMed] [Google Scholar]
  20. O'Brasky J. E., Crandall E. D. Organ and species differences in tissue vascular carbonic anhydrase activity. J Appl Physiol Respir Environ Exerc Physiol. 1980 Aug;49(2):211–217. doi: 10.1152/jappl.1980.49.2.211. [DOI] [PubMed] [Google Scholar]
  21. O'Brasky J. E., Mauro T., Crandall E. D. Postcapillary pH disequilibrium after gas exchange in isolated perfused liver. J Appl Physiol Respir Environ Exerc Physiol. 1979 Nov;47(5):1079–1083. doi: 10.1152/jappl.1979.47.5.1079. [DOI] [PubMed] [Google Scholar]
  22. Obaid A. L., Crandall E. D. HCO3-/Cl- exchange across the human erythrocyte membrane: effects of pH and temperature. J Membr Biol. 1979 Oct 5;50(1):23–41. doi: 10.1007/BF01868786. [DOI] [PubMed] [Google Scholar]
  23. Percy A. K., Miller M. E. Reduced deformability of erythrocyte membranes from patients with Duchenne muscular dystrophy. Nature. 1975 Nov 13;258(5531):147–148. doi: 10.1038/258147a0. [DOI] [PubMed] [Google Scholar]
  24. Wieth J. O., Brahm J. Salicylats haemmende virkning på klorid- og bikarbonattransport i røode blodlegemer. En mulig forklaring på salicylaters respirationsstimulerende virkning. Ugeskr Laeger. 1978 Jul 31;140(31):1859–1865. [PubMed] [Google Scholar]
  25. Wieth J. O. Effect of some monovalent anions on chloride and sulphate permeability of human red cells. J Physiol. 1970 May;207(3):581–609. doi: 10.1113/jphysiol.1970.sp009082. [DOI] [PMC free article] [PubMed] [Google Scholar]

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