Pulmonary entrapment of sickle cells: the role of regional alveolar
hypoxia.
Aldrich, Thomas K., Sunil K. Dhuper, Najmuddin S. Patwa, Eric Makolo,
Sandra M. Suzuka, Shamim A. Najeebi, Sunil Santhanakrishnan, Ronald
L. Nagel, and Mary E. Fabry.
Pulmonary Medicine and Hematology Divisions, Department of
Medicine, Montefiore Medical Center and Albert Einstein College of
Medicine, Bronx, New York
APStracts 2:0448A, 1995.
Pulmonary microvascular occlusion by abnormally adherent and/or
nondeformable sickle red cells (SS cells) may contribute to the
pathogenesis of acute chest syndrome of sickle cell disease. We
hypothesized that regional alveolar hypoxia reduces SS cell
deformability, and, by causing regional vasoconstriction, slows
regional perfusion, facilitating endothelial adhesion and mechanical
entrapment of cells. In isolated rat lungs perfused at constant
average flow with physiologic salt solution, we separately ventilated
the two lungs, one with 95% O2, the other with 0, 2.5, 5, or 21% O2.
We infused a bolus of 99mTc-labelled SS cells or normal human AA
cells along with 113Sn-labelled 15[mu] microspheres as a perfusion
marker, then sliced the lungs and counted 99mTc and 113Sn. Weight
-normalized perfusion decreased with hypoxia (p<.02). Retention
of AA cells (perfusion-normalized) averaged about 1% in lungs
ventilated with 95% oxygen and increased only 2-fold with 0% O2. In
contrast, retention of SS cells averaged 3-fold higher than that of
AA cells at 95% and 5% O2, 15-fold higher at 2.5% O2, and 25-fold
higher at 0% O2 (p<.01). Histologic examination demon strated
entrapment of individual SS cells entrapped in alveolar capillaries
of hypoxic but not well-oxygenated lungs. Relief of hypoxia, but not
increased perfusate flow, caused prompt efflux of most entrapped
cells, which were primarily high-density (high MCHC) cells. Thus,
substantial retention of SS cells does not occur without hypoxia, but
regional hypoxia and/or the resulting vasoconstriction cause
extraordinary regional retention of dense SS cells, a phenomenon that
appears to be due more to mechanical entrapment of non-deformable
cells in capillaries than to endothelial adhesion.
Received 14 October 1994; accepted in final form 18 September
1995.
APS Manuscript Number A1060-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95