Aprotinin attenuates genomic expression variability following cardiac surgery.
BACKGROUND
Aprotinin was the subject of recent controversy regarding adverse clinical outcomes following cardiac surgery. We compared the role of Aprotinin and epsilon-aminocaproic acid on clinical outcomes and the attenuation of the postcardiopulmonary bypass (CPB) response at the genomic expression and cytokine (protein) level.


METHODS
Thirty-nine low-risk patients undergoing coronary revascularization (CABG) and/or valve procedures using cardiopulmonary CPB were enrolled into a prospective cohort study. Aprotinin or epsilon-aminocaproic acid was administered to patients. Gene expression was assessed from whole blood mRNA samples collected preoperatively (PRE) and 6 hours (6H) postoperatively. Validation of gene expression was performed with SYBR Green real-time polymerase chain reaction. Cytokine values were quantified from serum preoperatively and postoperatively at 6 H and 4 days and analyzed in a blinded fashion.


RESULTS
No difference was detected in baseline characteristics. Inflammatory markers measured did not reveal significant difference between patients receiving Aprotinin (APR) and those receiving epsilon-aminocaproic acid (Amicar). Intraoperative parameters and postoperative outcomes were not significantly different. Compared with PRE samples, 6H samples had 264 upregulated and 548 downregulated genes uniquely in the APR group compared to 4826 upregulated and 1114 downregulated genes uniquely in the Amicar group (p < 0.001). Compared to patients in the Amicar group, APR patients had significantly different gene expression pathways involving NF-kappabeta regulation, programmed cell death and cell-cell adhesion. None of the patients developed postoperative stroke, myocardial infarction, or systemic infections.


CONCLUSIONS
Aprotinin leads to significantly less genomic expression variability following CPB compared to Amicar and has a differential effect on specific genomic pathways.
Ramlawi
Basel
B
Division of Cardiothoracic Surgery, Columbia Presbyterian Medical Center, Columbia University, New York, New York, USA.
Otu
Hasan
H
Russo
Mark J
MJ
Novick
Richard J
RJ
Bianchi
Cesario
C
Sellke
Frank W
FW
D000368:Aged; D000614:Aminocaproates / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D007611:Aprotinin / Q000008:administration & dosage*; D002315:Cardiopulmonary Bypass; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015331:Cohort Studies; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D019918:Heart Valve Prosthesis Implantation; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D011292:Premedication; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000614:Aminocaproates; D016207:Cytokines; D006490:Hemostatics; D018836:Inflammation Mediators; D016328:NF-kappa B; D012333:RNA, Messenger; D007611:Aprotinin