Abstract
Normothermic Regional Perfusion (NRP) consists in a in situ reperfusion of organs and has been used as a novel resuscitation and procurement strategy to increase the use of donors after circulatory death (DCD) heart transplantation. Although already being used for heart donors clinically there is still no pre-clinical data showing the impact of this procedure in the donor lungs. The objective of this study was to determine lung quality for donation after NRP for heart preservation/assessment. During NRP for DCD heart procurement lungs physiological parameters were monitored. Donor pigs (N=5) following adequate anesthetic induction underwent hypoxic circulatory arrest followed by 15 minutes of warm ischemia and resuscitation with NRP. Central cannulation was used for NRP, supra-aortic vessels were cross-clamped, and anesthetic drugs were stopped leading to hypoxemic cardiac arrest. Lung assessment was performed before DCD induction as baseline and at 15,45 min and after weaning NRP. Ventilation settings were pressure control of 15 cmH2O with FiO2 at 50%, PEEP of 5cmH2O, respiratory rate of 15 - same as used for regular lung harvest. NRP was weaned after 1h and lung oxygenation function was obtained from systemic blood samples. Lung biopsies were sequentially taken for cytokine analyses at baseline and end of NRP (between 5 to 10 minutes after successfully weaning). Ventilation parameters as static and dynamic compliance were 50.6 (±5.1) and 48.2 (±5.5) ml/cmH2O before cannulation and 41.2 (± 3.2) and 37.6 (±2.5) by the end of NRP (p=0.43). ETCO2 (a marker of lung perfusion) measurements were 33.6 mmHg (±0.5) at baseline and 5.2 mmHg (±3.8) during NRP. Mean systemic PO2/FiO2 was 439mmHg (±58.7) as baseline and 488.1 (±15.4) in the end after NRP wean. IL-6 and IL-8 in tissue and plasma were measured at baseline and after weaning. Only tissue levels of IL-6 were significantly higher after wean(p=0.032), but overall levels were in very low concentration: baseline 0.0247 (±0.0123) and 0.0880 (±0.0217) pg/ml after weaning. During NRP for heart procurement gas exchange function is preserved before and after NRP and no statistical differences in pulmonary compliance is seen. Further studies transplanting lungs subjected to NRP should be performed before safe translation to clinical practice.
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