Effects of hemoglobin and cell membrane lipids on pulmonary surfactant activity.
These experiments characterize the effects of hemoglobin and erythrocyte membrane lipids on the dynamic surface activity and adsorption facility of whole lung surfactant (LS) and a calf lung surfactant extract (CLSE) used clinically in surfactant replacement therapy for the neonatal respiratory distress syndrome (RDS). The results show that, at concentrations from 25 to 200 mg/ml, hemoglobin (Hb) increased the minimum dynamic surface tension of LS or CLSE mixtures (0.5 and 1.0 mumol/ml) from less than 1 to 25 dyn/cm on an oscillating bubble apparatus at 37 degrees C. Similarly, erythrocyte membrane lipids (0.5-3 mumol/ml) also prevented LS and CLSE suspensions (0.5-2.0 mumol/ml) from lowering surface tension below 19 dyn/cm under dynamic compression on the bubble. Surface pressure-time adsorption isotherms for LS suspensions (0.084 and 0.168 mumol phospholipid/ml) were also adversely affected by Hb (0.3-2.5 mg/ml), having a slower adsorption rate and magnitude. Significantly, these inhibitory effects of Hb and membrane lipids could be abolished if LS and CLSE concentrations were raised to high levels. In complementary physiological experiments, instillation of Hb, membrane lipids, or albumin into excised rat lungs was shown to cause a decrease in pressure-volume compliance. This decreased compliance was most prominent in lungs made partially surfactant deficient before inhibitor delivery and could be reversed by supplementation with active exogenous surfactant. Taken together, these data show that molecular components in hemorrhagic pulmonary edema can biophysically inactivate endogenous LS and adversely affect lung mechanics. Moreover, exogenous surfactant replacement can reverse this process even in the continued presence of inhibitor molecules and thus has potential utility in therapy for adult as well as neonatal RDS.
Department of Biophysics (Toxicology) and Pediatrics (Neonatology), University of Rochester, New York 14642.
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Holm
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Notter
D000327:Adsorption; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002417:Cattle; D004910:Erythrocyte Membrane / Q000502:physiology; D006454:Hemoglobins / Q000502:physiology*; D066298:In Vitro Techniques; D008168:Lung / Q000502:physiology; D008563:Membrane Lipids / Q000097:blood / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000502:physiology; D013500:Surface Tension
D006454:Hemoglobins; D008563:Membrane Lipids; D011663:Pulmonary Surfactants; D012710:Serum Albumin, Bovine