Antifibrinolytics attenuate inflammatory gene expression after cardiac surgery

Area of Science:

• Molecular Biology
• Immunology
• Pharmacology

Background:

• Tranexamic acid and aprotinin are used to reduce perioperative blood loss.
• Their anti-inflammatory effects may have significant clinical implications.
• Messenger ribonucleic acid (mRNA) synthesis analysis is key to understanding inflammatory pathways.

Purpose of the Study:

• To investigate the anti-inflammatory effects of tranexamic acid and aprotinin.
• To analyze changes in inflammatory gene expression post-surgery.
• To compare the genomic impact of these antifibrinolytics.

Main Methods:

• Randomized controlled trial involving 35 patients.
• Comparison of whole-blood mRNA expression of 114 inflammatory genes pre- and post-surgery.
• Patients received placebo, tranexamic acid, or aprotinin.
• Results confirmed by reverse transcription-polymerase chain reaction (RT-PCR).

Main Results:

• Twenty-three genes showed altered postoperative expression.
• Eight genes were uniquely affected by aprotinin.
• Both aprotinin and tranexamic acid altered three genes compared to placebo.
• Antifibrinolytic treatment generally showed less pro-inflammatory and more anti-inflammatory gene upregulation.
• Aprotinin primarily affected genes encoding serine protease-related proteins.

Conclusions:

• Tranexamic acid and aprotinin alter inflammatory pathways at the genomic expression level.
• Aprotinin significantly attenuates the immune response, with some effects exclusive to its use.
• Findings enhance understanding of antifibrinolytic drug targets and inform clinical decisions in cardiac surgery.