Aprotinin attenuates genomic expression variability following cardiac surgery

Basel Ramlawi, Hasan Otu, Mark J. Russo, Richard J. Novick, Cesario Bianchi, Frank W. Sellke

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Aprotinin was the subject of recent controversy regarding adverse clinical outcomes following cardiac surgery. We compared the role of Aprotinin and ε-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 ε-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 ε-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-κbeta 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.

Original languageEnglish (US)
Pages (from-to)772-780
Number of pages9
JournalJournal of Cardiac Surgery
Volume24
Issue number6
DOIs
StatePublished - Nov 1 2009

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Aprotinin
Aminocaproic Acid
Thoracic Surgery
Gene Expression
Down-Regulation
Cytokines
Cell Adhesion
Genes
Real-Time Polymerase Chain Reaction
Cohort Studies
Cell Death
Stroke
Myocardial Infarction
Prospective Studies
Messenger RNA
Infection
Serum

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Aprotinin attenuates genomic expression variability following cardiac surgery. / Ramlawi, Basel; Otu, Hasan; Russo, Mark J.; Novick, Richard J.; Bianchi, Cesario; Sellke, Frank W.

In: Journal of Cardiac Surgery, Vol. 24, No. 6, 01.11.2009, p. 772-780.

Research output: Contribution to journalArticle

Ramlawi, Basel ; Otu, Hasan ; Russo, Mark J. ; Novick, Richard J. ; Bianchi, Cesario ; Sellke, Frank W. / Aprotinin attenuates genomic expression variability following cardiac surgery. In: Journal of Cardiac Surgery. 2009 ; Vol. 24, No. 6. pp. 772-780.
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