Platelet activating factor inhibition reduces lung injury after cardiopulmonary bypass.
Because cardiopulmonary bypass (CPB) produces a diffuse inflammatory reaction that may injure multiple organs and complicate cardiac surgical procedures, we examined the use of a competitive inhibitor of platelet activating factor (SDZ HUL-412) in a porcine model of CPB as a means to ameliorate pulmonary injury after CPB. Thirteen pigs (35 to 40 kg) underwent CPB at 28 degrees C for 2 hours, followed by 2 hours of observation. Group I (n = 6) received SDZ HUL-412 (a quinolinium compound) intravenously (3 mg/kg loading dose and 2 mg.kg-1.h-1 continuous infusion) starting before sternotomy. Group II (n = 7) received a saline vehicle. Peak airway pressure, pulmonary arterial pressure, left atrial pressure, and arterial blood gases were measured and flow cytometry evaluated surface expression of adhesion molecule subunit CD18 on circulating neutrophils. Pulmonary function was significantly improved in group I. Fifteen minutes after CPB, dynamic lung compliance in group I was 91% +/- 12% of baseline versus 49% +/- 5.2% in group II (p = 0.06 by analysis of variance). After CPB, the arterial oxygen pressure was also significantly better in group I than in group II (425 +/- 61 versus 234 +/- 76 mm Hg) (p < 0.05). The rise in pulmonary vascular resistance after CPB was less in group I (p < 0.05) (323 +/- 55 to 553 +/- 106 dynes.s.cm-5) than in group II (531 +/- 177 to 884 +/- 419 dynes.s.cm-5) at the end of the observation period. CD18 up-regulation increased similarly in the two groups during CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
Division of Cardiac Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland.
K J
KJ
Zehr
R S
RS
Poston
P C
PC
Lee
K
K
Uthoff
P
P
Kumar
P W
PW
Cho
A M
AM
Gillinov
J M
JM
Redmond
J A
JA
Winkelstein
A
A
Herskowitz
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001772:Blood Cell Count; D018821:CD18 Antigens / Q000032:analysis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D008168:Lung / Q000473:pathology; D008170:Lung Compliance; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D011652:Pulmonary Circulation; D011806:Quinolinium Compounds / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014655:Vascular Resistance
D018821:CD18 Antigens; D010972:Platelet Activating Factor; D011806:Quinolinium Compounds; C091901:SDZ HUL-412; D000244:Adenosine Diphosphate