Oxygen free radicals mediate ischemia-induced lung injury.
Lower torso ischemia leads during reperfusion to leukocyte (white blood cell)-dependent lung injury. This study tests the intermediary role of oxygen free radicals (OFRs) in mediating this event. Chronically instrumented anesthetized sheep underwent 2 hours of bilateral hindlimb ischemia. In untreated control animals (n = 7), 1 minute after tourniquet release, mean pulmonary artery pressure rose from 13 to 38 mm Hg (p less than 0.05), whereas pulmonary artery wedge pressure was unchanged from 4 mm Hg. The pulmonary hypertension was temporally related to an increase in plasma thromboxane (Tx) B2 levels from 211 to 735 pg/ml (p less than 0.05). At 30 minutes of reperfusion lung-lymph TxB2 levels rose from 400 to 1005 pg/ml (p less than 0.05). This coincided with an increase in lung-lymph flow from 4.3 to 8.3 ml/30 min (p less than 0.05), which remained elevated for 2 hours, an unchanged lymph/plasma protein ratio, and a rise in lymph protein clearance from 2.6 to 4.6 ml/30 min (p less than 0.05). These changes are consistent with increased lung microvascular permeability. White blood cell count fell during the first hour of reperfusion from 6853 to 3793/mm3 (p less than 0.05), and lung histologic findings showed marked leukosequestration relative to sham animals (n = 3). Pretreatment with the OFR scavengers, superoxide dismutase and catalase both conjugated to polyethylene glycol (n = 6) blunted the rise in mean pulmonary artery pressure to 19 mm Hg (P less than 0.05) and prevented the increase in plasma and lymph TxB2 lymph flow, and lymph protein clearance (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Klausner
J M
JM
Department of Surgery, Brigham and Women's Hospital, Boston, Mass. 02115.
Paterson
I S
IS
Kobzik
L
L
Valeri
C R
CR
Shepro
D
D
Hechtman
H B
HB
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000494:pharmacology; D005260:Female; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007958:Leukocyte Count; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010976:Platelet Count; D012756:Sheep; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013929:Thromboxane B2 / Q000097:blood
D005609:Free Radicals; D013481:Superoxides; D013929:Thromboxane B2; D000493:Allopurinol; D002374:Catalase; D013482:Superoxide Dismutase