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.

Correlation between the physiologic and morphologic changes in experimental autoimmune uveitis induced by peptide G of S-antigen.

PURPOSE: The authors followed and correlated the physiologic and morphologic changes occurring in experimental autoimmune uveitis (EAU) induced by the peptide G of S-antigen. METHODS: EAU was induced in Lewis rats by footpad inoculation of a 13-amino acid synthetic peptide (peptide G) in complete Freund's adjuvant. Electroretinography (ERG) was used to follow the physiologic changes, and light and electron microscopy were used to examine the morphologic changes. RESULTS: Serial ERG recordings showed a progressive decrease in the b-wave amplitude and a depression of retinal sensitivity beginning on day 18-21 postinoculation (PI). By day 35 PI, the b-wave was decreased by 91%, and the sensitivity was depressed by 4.68 log units. Negative ERG were recorded during the intermediate and late stage. Light and electron microscopy of the retina showed better correlation of the pathologic changes with b-wave depression than with PI day. CONCLUSIONS: ERG recordings were a good method to detect, follow, and quantify the severity of EAU. Their good correlation with the morphologic changes showed that this method can be used to assess the condition of the retina noninvasively.