Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury

ObjectiveCustodiol (histidine-tryptophan-ketoglutarate solution) is a leading organ preservation solution. On the basis of this solution, the novel Custodiol-N was developed. The present study investigated the effects of Custodiol-N in a rat model of heart transplantation.MethodsHeterotopic heart transplantation was performed in Lewis rats. Four groups were assigned: 2 Custodiol-N–treated groups and 2 Custodiol-treated control groups with a reperfusion time of 1 hour and 24 hours, respectively. Coronary blood flow, left ventricular pressure, its first derivative, left ventricular end-diastolic pressure, endothelium-dependent vasodilatation to bradykinin and endothelium-independent vasodilatation to sodium nitroprusside, and adenosine triphosphate content were measured. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining was performed to detect apoptotic cardiomyocytes.ResultsAfter 1 hour, coronary blood flow (3.99 ± 0.24 mL/min/g vs 2.86 ± 0.35 mL/min/g; P < .05), left ventricular pressure (117 ± 18 mm Hg vs 82 ± 4 mm Hg; P < .05), and first derivative of left ventricular pressure (3453 ± 577 mm Hg/s vs 1740 ± 116 mm Hg/s; P < .05) were significantly higher in the Custodiol-N group compared with the corresponding control. The left ventricular systolic pressure–volume relationship was significantly steeper, indicating improved contractility. Vasodilatatory response to sodium nitroprusside did not show any major differences between the groups. Response to bradykinin resulted in a significantly higher increase in coronary blood flow in the Custodiol-N group (92% ± 4% vs 60% ± 5%; P < .05). Myocardial adenosine triphosphate content was significantly higher in the Custodiol-N group (9.84 ± 0.68 μmol/g vs 1.86 ± 0.41 μmol/g; P < .05). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining showed a significantly reduced apoptosis level (21.58% ± 1.59% vs 27.23% ± 1.54%; P < .05) in the Custodiol-N group.ConclusionCustodiol-N improves myocardial and endothelial function during the critical phase of reperfusion after heart transplantation.