Molecular Genetics of Lidocaine-Containing Cardioplegia in the Human Heart During Cardiac Surgery

Ann Thorac Surg. 2018 Nov;106(5):1379-1387. doi: 10.1016/j.athoracsur.2018.06.016. Epub 2018 Jul 17.

Abstract

Background: During cardiac surgery with cardiopulmonary bypass, delivery of cardioplegia solution to achieve electromechanical cardiac quiescence is obligatory. The addition of lidocaine to cardioplegia has advantages, although its consequences at a molecular level remain unclear. We performed whole-genome RNA sequencing of the human left ventricular (LV) myocardium to elucidate the differences between whole-blood (WB) cardioplegia with and without addition of lidocaine (LC) on gene expression.

Methods: We prospectively enrolled 130 patients undergoing aortic valve replacement surgery. Patients received high-potassium blood cardioplegia either with (n = 37) or without (n = 93) lidocaine. The LV apex was biopsied at baseline, and after an average of 74 minutes of cold cardioplegic arrest. We performed differential gene expression analysis for 18,258 genes between these 2 groups. Clinical and demographic variables were adjusted in the model. Gene ontology (GO) and network enrichment analysis of the retained genes were performed using g:Profiler and Cytoscape.

Results: A total of 1,298 genes were differentially expressed between cardioplegic treatments. Compared with the WB group, genes upregulated in the LC group were identified by network enrichment to play a protective role in ischemic injury by inhibiting apoptosis, increasing transferrin endocytosis, and increasing cell viability. Downregulated genes in the LC group were identified to play a role in inflammatory diseases, oxygen transport, and neutrophil aggregation.

Conclusions: The addition of lidocaine to cardioplegia had pronounced effects on a molecular level with genes responsible for decreased inflammation, reduced intracellular calcium binding, enhanced antiapoptotic protection, augmented oxygen accessibility through transferrins, and increased cell viability showing measurable differences.

Publication types

  • Comparative Study

MeSH terms

  • Academic Medical Centers
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aortic Valve / physiopathology
  • Aortic Valve / surgery*
  • Cardiac Surgical Procedures / methods*
  • Cardiac Surgical Procedures / mortality
  • Cardioplegic Solutions / administration & dosage
  • Cardiopulmonary Bypass / methods
  • Cardiopulmonary Bypass / mortality
  • Cohort Studies
  • Gene Expression Regulation
  • Heart Arrest, Induced / methods*
  • Heart Valve Prosthesis Implantation / methods*
  • Heart Valve Prosthesis Implantation / mortality
  • Humans
  • Lidocaine / administration & dosage*
  • Male
  • Middle Aged
  • Molecular Biology
  • Reference Values
  • Retrospective Studies
  • Risk Assessment
  • Treatment Outcome

Substances

  • Cardioplegic Solutions
  • Lidocaine