Effects of stroma-free hemoglobin solutions on pulmonary vascular resistance and mediator release in the isolated perfused rabbit lung.
The aim of this study was to evaluate the effect of an ultrapure bovine stroma-free hemoglobin (SFH) on pulmonary vascular resistance and mediator release and to analyze potential mechanisms of action in the isolated perfused rabbit lung model. Repetitive bolus applications of small amounts of bovine SFH were examined which resulted in a reproducible acute increase of pulmonary vascular resistance of approx. 9 mmHg (controls, n = 6). It was tested whether the platelet-activating factor (PAF) antagonist WEB 2086 (50 microM; n = 6), the cyclooxygenase blocker diclofenac (10 micrograms/ml; n = 6), the iron-chelating agent deferoxamine (500 micrograms/ml, n = 6) and the radical scavenger catalase (5000 U/ml; n = 6) exert a protective effect on vasoconstrictor response to SFH. The pressure increase was completely suppressed in the lungs pretreated with WEB 2086, whereas diclofenac, deferoxamine and catalase failed to inhibit the vasoconstriction due to SFH. No significant differences in either TXB2 generation or in histamine release were found in the WEB 2086 group compared with untreated lungs. The results point towards the crucial role of PAF in mediation of vasoconstrictor side effects due to SFH.
Koch
T
T
Department of Anesthesiology and Operative Intensive Care, Faculty for Clinical Medicine Mannheim, University of Heidelberg, Germany.
Duncker
H P
HP
Heller
A
A
Schaible
R
R
van Ackern
K
K
Neuhof
H
H
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D003676:Deferoxamine / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006454:Hemoglobins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D006636:Histamine Release / Q000187:drug effects*; D007501:Iron; D008297:Male; D010477:Perfusion; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000096:biosynthesis; D014230:Triazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D001381:Azepines; D016166:Free Radical Scavengers; D006454:Hemoglobins; D010972:Platelet Activating Factor; D014230:Triazoles; C052518:WEB 2086; D004008:Diclofenac; D013929:Thromboxane B2; D007501:Iron; D002374:Catalase; D003676:Deferoxamine