Exploring effects of remote ischemic preconditioning in a pig model of hypothermic circulatory arrest

Scand Cardiovasc J. 2017 Aug;51(4):233-241. doi: 10.1080/14017431.2017.1319574. Epub 2017 Apr 24.

Abstract

Objectives: During aortic and cardiac surgery, risks for mortality and morbidity are inevitable. Surgical setups involving deep hypothermic circulatory arrest (DHCA) are effective to achieve organ protection against ischemic injury. The aim of this study was to identify humoural factors mediating additive protective effects of remote ischemic preconditioning (RIPC) in a porcine model of DHCA.

Design: Twenty-two pigs were randomized into the RIPC group (n = 11) and the control group (n = 11). The RIPC group underwent four 5-minute hind limb ischemia-reperfusion cycles prior to cardiopulmonary bypass and DHCA. All animals underwent identical surgical procedures including 60 min DHCA at 18 °C. Blood samples were collected from vena cava and sagittal sinus at several time points. After the 8-hour follow-up period, the brain, heart, and kidney tissue samples were collected for tissue analyses.

Results: Serum levels of brain damage marker S100B recovered faster in the RIPC group, after 4 hours of the arrest, (p < .05). Systemic lactate levels were lower and cardiac index was higher in the RIPC group postoperatively. Immunohistochemical cerebellum regional scores of antioxidant response regulator Nrf2 were better in the RIPC group (mean: 1.1, IQR: 0.0-2.5) compared with the control group (mean: 0.0, IQR: 0.0-0.0), reaching borderline statistical significance (p = .064). RIPC induced detectable modulations of plasma proteome and metabolites.

Conclusions: The faster recovery of S100B, lower systemic lactate levels and favourable regional antioxidant response suggest possible neuronal cellular and mitochondrial protection by RIPC, whereas better cardiac index underlines functional effects of RIPC. The exact humoural factor remains unclear.

Keywords: Remote ischemic preconditioning; humoural factors; hypothermic circulatory arrest.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Biomarkers / blood
  • Brain / metabolism
  • Brain / pathology
  • Cardiopulmonary Bypass
  • Circulatory Arrest, Deep Hypothermia Induced*
  • Disease Models, Animal
  • Female
  • Hindlimb / blood supply*
  • Ischemic Preconditioning, Myocardial / methods*
  • Ketoglutaric Acids / blood
  • Kynurenic Acid / blood
  • Lactic Acid / blood
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Myocardial Reperfusion Injury / blood
  • Myocardial Reperfusion Injury / pathology
  • Myocardial Reperfusion Injury / prevention & control*
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-E2-Related Factor 2 / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Proteomics / methods
  • Regional Blood Flow
  • S100 Calcium Binding Protein beta Subunit / blood
  • Sus scrofa
  • Time Factors

Substances

  • Antioxidants
  • Biomarkers
  • Ketoglutaric Acids
  • NF-E2-Related Factor 2
  • S100 Calcium Binding Protein beta Subunit
  • Lactic Acid
  • Kynurenic Acid