Effects of atrial natriuretic peptide after prolonged hypothermic storage of the isolated rat heart

Primary graft failure (PGF) caused by ischemia-reperfusion injury (IRI) is the strongest determinant of perioperative mortality after heart transplantation. Atrial natriuretic peptide (ANP) has been found to reduce the IRI of cardiomyocytes and may be beneficial in alleviating PGF after heart transplantation, although there is a lack of evidence to support this issue. The purpose of this study was to investigate the cardioprotective effects of ANP after prolonged hypothermic storage. For this purpose, an isolated working-heart rat model was used. After the preparation, the hearts were arrested with and stored in an extracellular-based cardioplegic solution at 3-4°C for 6h and followed by 25min of reperfusion. The hearts were divided into four groups (n=7 in each group) according to the timing of ANP administration: Group 1 (in perfusate before storage), Group 2 (in cardioplegia), Group 3 (in reperfusate), and control (no administration of ANP). Left ventricular functional recovery and the incidence of ventricular fibrillation (VF) were compared. ANP administration at the time of reperfusion improved the percent recovery of left ventricular developed pressure (control, 45.5±10.2; Group 1, 47.4±8.8; Group 2, 45.3±12 vs. Group 3, 76.3±7; P<0.05) and maximum first derivative of the left ventricular pressure (control, 47.9±8.7; Group 1, 46.7±8.8; Group 2, 49.6±10.8 vs. Group 3, 76.6±7.5; P<0.05). The incidence of VF after reperfusion did not differ significantly among these four groups (71.4, 85.7, 57.1, and 85.7% in Groups 1, 2, 3, and control, respectively). This result suggests that the administration of ANP at the time of reperfusion may have the potential to decrease the incidence of PGF after heart transplantation.