HEMO₂life as a protective additive to Celsior solution for static storage of donor hearts prior to transplantation

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

Disclosure statement

F.Z. is founder and hold stock in HEMARINA SA, which produces the substance being investigated. V.P. is an employee of HEMARINA SA and does not hold stock. All other authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.