Conebulization of surfactant and urokinase restores gas exchange in perfused lungs with alveolar fibrin formation.
Alveolar fibrin generation has been suggested to possess strong surfactant-inhibitory potency. In perfused rabbit lungs, fibrin formation in the alveolar space was induced by sequential ultrasonic aerosolization of fibrinogen and thrombin, and the efficacy of rescue administration of surfactant and urokinase was investigated. Ventilation-perfusion (VA/Q) distribution was assessed by the multiple inert gas elimination technique. Aerosolization of fibrinogen (approximately 20 mg/kg body wt) increased shunt flow to approximately 7%. Sequential nebulization of fibrinogen and thrombin (1.3 U/kg body wt) caused alveolar fibrin deposition, documented immunohistologically, and provoked marked shunt flow, progressing to approximately 22% at the end of the experiments. The hemodynamics were virtually unchanged. Rescue aerosolization of natural bovine surfactant (15 mg/kg body wt) or urokinase-type plasminogen activator (4,500 U/kg body wt), undertaken after fibrin formation, improved gas exchange but progressive shunt flow still occurred (efficacy, surfactant > urokinase). In contrast, conebulization of surfactant and urokinase reversed shunt flow to approximately 7%, with an increased appearance of normal VA/Q matching. We conclude that alveolar fibrin formation is a potent surfactant-inhibitory mechanism in intact lungs, provoking severe VA/Q mismatch with a predominance of shunt flow, and that rescue aerosolization of surfactant plus urokinase may offer restoration of gas exchange under these conditions.
Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, D-35392 Giessen, Germany. ralph.schermuly@innere.med.uni-giessen.de
R T
RT
Schermuly
A
A
Günther
M
M
Ermert
L
L
Ermert
H A
HA
Ghofrani
N
N
Weissmann
F
F
Grimminger
W
W
Seeger
D
D
Walmrath
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004357:Drug Synergism; D005337:Fibrin / Q000096:biosynthesis*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects; D009330:Nebulizers and Vaporizers; D010477:Perfusion; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000008:administration & dosage* / Q000494:pharmacology; D011817:Rabbits; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage* / Q000494:pharmacology; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects
D005338:Fibrin Fibrinogen Degradation Products; D011663:Pulmonary Surfactants; C036309:fibrin fragment D; D012965:Sodium Chloride; D005337:Fibrin; D005340:Fibrinogen; D014568:Urokinase-Type Plasminogen Activator