X-Message-Number: 16163 Date: Mon, 30 Apr 2001 16:45:39 -0400 From: James Swayze <> Subject: Some research I stumbled onto regarding ischemia From Nature online: Abstract may be viewed here: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v7/n5/abs/nm0501_598.html May 2001 Volume 7 Number 5 pp 598 - 604 Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis Tomoyuki Fujita1, Koichi Toda1, Ann Karimova1, Shi-Fang Yan1, Yoshifumi Naka1, Shaw-Fang Yet2 & David J. Pinsky1 Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to ischemic stress. Ho-1 deficient (Hmox1-/-) mice exhibited lethal ischemic lung injury, but were rescued from death by inhaled CO. CO drove ischemic protection by activating soluble guanylate cyclase and thereby suppressed hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (PAI-1) in mononuclear phagocytes, which reduced accrual of microvascular fibrin. CO-mediated ischemic protection observed in wild-type mice was lost in mice null for the gene encoding PAI-1 (Serpine1). These data establish a fundamental link between CO and prevention of ischemic injury based on the ability of CO to derepress the fibrinolytic axis. These data also point to a potential therapeutic use for inhaled CO. 1. Columbia University, College of Physicians and Surgeons, New York, New York, USA 2. Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA Correspondence should be addressed to D J Pinsky. e-mail: Hope this is valuable to someone here. James -- Some of our views are spacious some are merely space--RUSH Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=16163