St Thomas' Hospital polarizing blood cardioplegia improves hemodynamic recovery in a porcine model of cardiopulmonary bypass

J Thorac Cardiovasc Surg. 2019 Dec;158(6):1543-1554.e8. doi: 10.1016/j.jtcvs.2018.11.104. Epub 2018 Dec 12.

Abstract

Objective: Cardiac surgery demands highly effective cardioprotective regimens. We previously demonstrated improved cardioprotection with "polarized" compared with "depolarized" arrest. This study uses a clinically relevant porcine model of cardiopulmonary bypass to compare the efficacy of blood-based St Thomas' Hospital polarizing cardioplegia (STH-Pol-B) with blood-based St Thomas' Hospital hyperkalemic cardioplegia (STH2-B).

Methods: Pigs were monitored and subjected to normothermic cardiopulmonary bypass, cardiac arrest via antegrade cold (4°C) blood cardioplegia (STH2-B, control group: n = 6 or STH-Pol-B, study group: n = 7), and global ischemia (60 minutes) followed by on-pump reperfusion (60 minutes) and subsequent off-pump reperfusion (90 minutes). At termination, tissue samples were taken for analysis of high-energy phosphates, ultrastructure, and microRNAs. The primary endpoint of this study was creatine kinase-muscle/brain release during reperfusion.

Results: Creatine kinase-muscle/brain was comparable in both groups. After pigs were weaned from cardiopulmonary bypass, hemodynamic parameters such as mean arterial pressure (P = .007), left ventricular systolic pressure (P < .001), external heart work (P = .012), stroke volume (P = .015), as well as dp/dtmax (P = .027), were improved with polarizing cardioplegia. Wedge pressure was significantly lower in the study group (P < .01). Energy charge was comparable between groups. MicroRNA-708-5p was significantly lower (P = .019) and microRNA-122 expression significantly (P = .046) greater in STH-Pol-B hearts.

Conclusions: Polarized cardiac arrest offers similar myocardial protection and enhances functional recovery in a porcine model of cardiopulmonary bypass. Differential expression of microRNAs may indicate possible new ischemia-reperfusion markers. These results confirm the noninferiority and potential of polarized versus depolarized arrest.

Keywords: St Thomas' Hospital No. 2; animal study; blood cardioplegia; cardioplegia; cardioprotection; cardiopulmonary bypass; ischemia-reperfusion; micro RNA; polarizing cardioplegia.

Publication types

  • Comparative Study
  • Video-Audio Media

MeSH terms

  • Animals
  • Bicarbonates / pharmacology
  • Biomarkers / blood
  • Calcium Chloride / pharmacology
  • Cardioplegic Solutions / pharmacology*
  • Cardiopulmonary Bypass* / adverse effects
  • Circulatory Arrest, Deep Hypothermia Induced* / adverse effects
  • Creatine Kinase, MB Form / blood
  • Energy Metabolism / drug effects
  • Female
  • Hemodynamics / drug effects*
  • Magnesium / pharmacology
  • MicroRNAs / metabolism
  • Models, Animal
  • Myocardium / metabolism
  • Myocardium / pathology
  • Potassium Chloride / pharmacology
  • Recovery of Function
  • Sodium Chloride / pharmacology
  • Sus scrofa
  • Time Factors
  • Ventricular Function, Left / drug effects*

Substances

  • Bicarbonates
  • Biomarkers
  • Cardioplegic Solutions
  • MicroRNAs
  • St. Thomas' Hospital cardioplegic solution
  • Sodium Chloride
  • Potassium Chloride
  • Creatine Kinase, MB Form
  • Magnesium
  • Calcium Chloride