The role of different types of corticosteroids on the inflammatory mediators in cardiopulmonary bypass.
In a placebo-controlled double-blind study on patients undergoing cardiopulmonary bypass (CPB) we studied the inhibiting effects of dexamethasone, a high dose of methylprednisolone, and a low dose of prednisolone on the inflammatory reaction induced by CPB. During CPB two episodes of blood activation were noticed. First, the blood-material interaction caused a significant increase in complement C3a and elastase concentrations after the start of bypass (p less than 0.01). Secondly, the reperfusion of the ischemic heart, lungs, and peripheral tissue, after release of the aortic cross-clamp, caused an additional increase in C3a and elastase concentration and a statistically significant increase in leukotriene B4 (LTB4) concentration and tissue plasminogen activator (t-PA) activity (p less than 0.01, p less than 0.05, respectively). Dexamethasone treatment effectively inhibited the increase in LTB4 concentration and t-PA activity after release of the cross-clamp (significant differences to the placebo group, p less than 0.01, p less than 0.05, respectively). High-dose methylprednisolone treatment was almost as effective as dexamethasone treatment, whereas low-dose prednisolone treatment was less effective than methylprednisolone in the inhibition of the inflammatory mediators (DM greater than MP greater than P). None of the corticosteroid regimens was able to inhibit the increase in complement C3a and elastase. We therefore conclude that corticosteroids do not have an effect on complement activation during CPB. However, leukocyte activation and t-PA activity after release of the aortic cross-clamp are effectively inhibited by corticosteroid treatment, in a dose-dependent way. The inhibition of this inflammatory reaction will have a favourable effect on the postoperative course in patients who have undergone CPB.
Jansen
N J
NJ
Department of Cardio-Pulmonary Surgery, University Hospital Groningen, The Netherlands.
van Oeveren
W
W
van Vliet
M
M
Stoutenbeek
C P
CP
Eysman
L
L
Wildevuur
C R
CR
D000209:Acute-Phase Proteins / Q000378:metabolism*; D000210:Acute-Phase Reaction / Q000276:immunology / Q000517:prevention & control*; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D002315:Cardiopulmonary Bypass; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D001026:Coronary Artery Bypass; D003907:Dexamethasone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D007975:Leukotriene B4 / Q000378:metabolism; D008775:Methylprednisolone / Q000008:administration & dosage; D010196:Pancreatic Elastase / Q000378:metabolism; D015849:Plasminogen Inactivators / Q000378:metabolism; D010976:Platelet Count / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage; D011292:Premedication; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D000209:Acute-Phase Proteins; D000305:Adrenal Cortex Hormones; D015849:Plasminogen Inactivators; D007975:Leukotriene B4; D003907:Dexamethasone; D002097:C-Reactive Protein; D011239:Prednisolone; D010196:Pancreatic Elastase; D010959:Tissue Plasminogen Activator; D008775:Methylprednisolone