Effect of a proteolytic enzyme inhibitor on the cardiopulmonary response to endotoxin

Pulmonary hypertension associated with cardiopulmonary bypass and cardiac surgery

“…Studies have demonstrated that CPB causes and/or is correlated with adhesion molecule expression, leukocyte activation, complement activation, the release of endotoxins, selectin‐mediated, neutrophil–endothelial interactions, and the release of many inflammatory mediators such as cytokines, oxygen‐free radicals, ETs, arachidonic acid metabolites, NO, and platelet‐activating factor 101 . Endotoxin is also correlated with increased levels of TXA2 102 …”

“…101 Endotoxin is also correlated with increased levels of TXA2. 102 There are several reasons for why the lungs may be vulnerable to injurious inflammation during cardiac surgery. 98 During CPB, lungs are one of the only organs to endure serious ischemia-reperfusion injury because of a lack or marked reduction in tissue perfusion.…”

Interaction of Inflammatory Mediators with the Lymphatic Vessel

“…While much is now known about the interactions of endo toxin with the arachidonate cascade [Demling et al, 1985[Demling et al, , 1986Adams and Traber, 1982;Flynn and Demling, 1982], these re ports give little clue to the potential role (if any) that arachidonate products play in regu lating interstitial dynamics through direct effects on lymphatic smooth muscle. There have been some attempts to study the effects of arachidonate or its metabolites on lymph flow [Joyner, 1977;Ogletree and Brigham, 1980;Smith et al, 1981b;Malik et al, 1985] and to block certain pathophysiological changes with arachidonic acid inhibitors [Adams and Traber, 1982;Patterson et al, 1985;Fukushima and Kobayashi, 1986] but the results have been interpreted solely on the basis of cardiovascular actions without considering the possibility that these agents may directly affect the lymph pump. In only one case that I am aware of [Bonsignore et al, 1986], did the investigators mention the possibility that suppression of arachidonate metabolism might affect lymphatic motility.…”