Myocardial neutrophil sequestration during reperfusion of the transplanted rabbit heart

Neutrophils are major participants in myocardial reperfusion injury, but the relationship between ischemic time and the extent of the neutrophil sequestration in heart transplantation has not yet been systematically studied. This study was designed to determine whether increased ischemic time would cause greater neutrophil sequestration during reperfusion of the globally ischemic heart.

Rabbit hearts were arrested with cardioplegia, explanted, and subjected to either 1 or 4 hours of global ischemia at 4 degrees C before being heterotopically transplanted into a recipient rabbit's abdomen for reperfusion. Each heart was reperfused for either 4, 8, or 12 hours. Between 3 and 7 hearts were studied (average = 5.8) for each combination of ischemic and reperfusion time (total = 35). A myeloperoxidase (MPO) assay was used to qualify neutrophil content.

MPO activity (U/g wet weight) was not significantly different at 4, 8, and 12 hours of reperfusion (0.33 +/- 0.05, 0.20 +/- 0.04, 0.26 +/- 0.04: p = 0.13), but was significantly increased at 4 hours compared to 1 hour ischemia (0.34 +/- 0.04 vs 0.19 +/- 0.03: p = 0. 006). Interaction between ischemic and reperfusion times was not significant (p = 0.12). MPO activity was below the measurable threshold in 5 freshly excised control hearts.

These results suggest that acute reperfusion injury will be more severe in the hearts subjected to 4 hours ischemia and indicate the need to consider neutrophil-mediated reperfusion injury when addressing cardioprotective interventions for cardiac preservation and reperfusion after transplantation. Neutrophil-mediated reperfusion injury of the rabbit myocardium after heterotopical transplantation is more severe in hearts subjected to 4 hours of ischemia vs 1 hour of ischemia prior to transplantation.