Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation.
BACKGROUND
Platelet-activating factor is a mediator of lung injury during cardiac operation. Platelet-activating factor antagonists reduce lung injury in animal models of cardiopulmonary bypass but there is no confirmatory evidence in clinical practice.


METHODS
The effect of a low or high dose of a platelet-activating factor antagonist (Lexipafant) was assessed in a single center, double-blind, placebo-controlled, parallel group study. One hundred fifty patients undergoing coronary artery bypass grafting were randomized by minimization into three groups to receive placebo infusion, 10 or 100 mg of lexipafant for over 24 hours. Serial arterial oxygen and carbon dioxide tension, alveolar arterial oxygen gradient, and percent saturation were measured before operation and at 1, 6, 24, 48 hours, and 5 days after operation.


RESULTS
Patient groups were similar with respect to age, sex, body surface area, and urgency of operation. Likewise, the groups were similar with respect to duration of cardiopulmonary bypass and the number and type of grafts. Maximum lung injury occurred at 48 hours when the arterial oxygen tension and percent saturation reached a nadir (both p < 0.001) accompanied by the maximum increase in the alveolar arterial gradient (p < 0.001). All measurements demonstrated partial recovery by 5 days but remained significantly (p < 0.001) impaired in comparison to baseline values. Duration of ventilation was similar in all groups. Lexipafant, at low or high dose, did not moderate lung injury after cardiopulmonary bypass and did not influence the duration of postoperative ventilation.


CONCLUSIONS
Despite experimental and clinical evidence implicating platelet-activating factor in the pathophysiology of lung injury after cardiopulmonary bypass, no beneficial effect of a platelet-activating factor antagonist on lung function or ventilation could be demonstrated in this clinical trial.
Taggart
D P
DP
Oxford Heart Centre, John Radcliffe Hospital, England. david.taggart@orh.anglox.nhs.uk
D000328:Adult; D000368:Aged; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007930:Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012131:Respiratory Insufficiency / Q000503:physiopathology* / Q000517:prevention & control
D007093:Imidazoles; D010972:Platelet Activating Factor; D007930:Leucine; C103289:lexipafant