HEMO 2 life as a protective additive to Celsior solution for static storage of donor hearts prior to transplantation

Artif Cells Nanomed Biotechnol. 2017 Jun;45(4):717-722. doi: 10.1080/21691401.2016.1265974. Epub 2017 Jan 12.

Abstract

Background: Prior to heart transplantation, static storage of donor hearts is currently limited to 4-5 h, despite profound hypothermia (4-8 °C). Because heart transplantation is an emergency procedure, improved protection to extend safe storage duration would be advantageous. We investigated whether the naturally respiratory pigment HEMO2life®, which is effective at hypothermia for the passive release of oxygen via oxygen gradient, could improve long-term preservation.

Methods: Isolated Langendorff-perfused rat hearts (n = 12/group) were equilibrated (20 min) and function (left ventricular developed pressure: LVDP) measured by intraventricular balloon before arrest with cold (7.5 °C) Celsior® solution, either alone (control) or with the addition of HEMO2life® (Hemarina SA, Morlaix, France) at 1 g/L. Cold storage lasted 8 h prior to reperfusion (60 min) and recovery (as % of pre-ischemic function) was assessed. Hearts (minced and homogenized) were also assessed by TTC staining as a measure of viability and two hearts from each group were sliced and assessed by TTC staining for infarct size. Values are expressed as mean ± standard error of mean and analyzed by Student's t-test.

Results: Hearts recovered rapidly in both groups to a plateau by 20 min of reperfusion; control and HEMO2life® final recovery (60 min) was 45 ± 2% and 57 ± 1% (P < 0.05) respectively. Left ventricular end-diastolic pressure recovered to a similar extent in both groups (between 31 to 35 mmHg), as did heart rate (final recovery between 84 to 89% pre-ischemic value); however, coronary flow was significantly (P < 0.05) higher in HEMO2life® group (7.5 ± 0.7 ml/min) compared to control (5.4 ± 0.4 ml/min). Viability and infarct size measurements were similar between groups.

Conclusion: The addition of the natural oxygen releasing pigment HEMO2life® to Celsior® preservation solution significantly improved post-ischemic recovery of heart function. This additive may have major therapeutic potential for clinical heart transplantation.

Keywords: Extracellular hemoglobin; heart graft preservation; langendorff model; oxygen carrier.

MeSH terms

  • Animals
  • Disaccharides / pharmacology
  • Electrolytes / pharmacology
  • Glutamates / pharmacology
  • Glutathione / pharmacology
  • Heart / drug effects*
  • Heart / physiology*
  • Heart / physiopathology
  • Heart Transplantation*
  • Histidine / pharmacology
  • Male
  • Mannitol / pharmacology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Preservation, Biological / methods*
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Solutions
  • Time Factors
  • Tissue Donors*
  • Tissue Survival / drug effects

Substances

  • Celsior
  • Disaccharides
  • Electrolytes
  • Glutamates
  • Solutions
  • Mannitol
  • Histidine
  • Glutathione