Pulmonary entrapment of sickle cells: the role of regional alveolar hypoxia.
Pulmonary microvascular occlusion by abnormally adherent and/or nondeformable sickle red blood 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 physiological salt solution, we separately ventilated the two lungs: one with 95% O2 and the other with 0, 2.5, 5, or 21% O2. We infused a bolus of 99mTc-labeled SS cells or normal human AA cells along with 113Sn-labeled 15-mu m microspheres as a perfusion marker, then sliced the lungs and counted 99mTc and 113Sn. Weight-normalized perfusion decreased with hypoxia (P < 0.02). Retention of AA cells (perfusion-normalized) averaged approximately 1% in lungs ventilated with 95% O2 and increased only twofold 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 < 0.01). Histological examination demonstrated entrapment of individual SS cells 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 mean corpuscular hemoglobin concentration) cells. Thus substantial retention of SS cells does not occur without hypoxia, but regional hypoxia and/or the resulting vasoconstriction causes extraordinary regional retention of dense SS cells, a phenomenon that appears to be due more to mechanical entrapment of nondeformable cells in capillaries than to endothelial adhesion.
Aldrich
T K
TK
Division of Pulmonary Medicine, Department of Medicine, Montefiore Medical Center, Bronx, New York 10467, USA.
Dhuper
S K
SK
Patwa
N S
NS
Makolo
E
E
Suzuka
S M
SM
Najeebi
S A
SA
Santhanakrishnan
S
S
Nagel
R L
RL
Fabry
M E
ME
D000755:Anemia, Sickle Cell / Q000097:blood / Q000503:physiopathology*; D000818:Animals; D004907:Erythrocyte Deformability / Q000502:physiology; D004913:Erythrocytes, Abnormal / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology*; D066298:In Vitro Techniques; D008168:Lung / Q000503:physiopathology*; D008297:Male; D010100:Oxygen / Q000097:blood; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013667:Technetium
D013667:Technetium; D010100:Oxygen