University of Wisconsin solution (UW) has been demonstrated to improve donor heart preservation. During reperfusion, however, myocardial performance may still remain limited by neutrophil (PMN)-mediated injury, manifested by the “low-reflow” phenomenon and myocardial “stunning.” Since PMN adhesion is an important mechanism of PMN-mediated injury, we tested whether blocking PMN adhesion molecule CD18 would enhance the efficacy of UW for 15-hr heart preservation. Rabbit hearts (n = 15) were arrested with, and preserved for 15 hr in, 4°C UW. After insertion of an left ventricular (LV) balloon, hearts were heterotopically transplanted into recipients pretreated with either intravenous (iv) saline (vehicle, n = 8) or iv anti-CD18 monoclonal antibody R15.7 (anti-CD18, n = 7). After 1 hr reperfusion the slope of the peak systolic pressure-volume (P-V) relation (Emax), the exponential coefficient (β), the volume-axis intercept (Vo) of the end-diastolic P-V relation, and the time constant of the exponential LV pressure decay after dP/dtmin (τ) were measured. Blood flow was measured with microspheres from which coronary vascular resistance (CVR) was calculated. Tissue %H2O was also measured. Between groups there were no significant differences in Emax (70.5 ± 6.1 vs 63.7 ± 6.0 mm Hg/ml, P > 0.05), β (3.3 ± 0.5 vs 4.3 ± 0.5, P > 0.05), Vo (-0.4 ± 0.1 vs -0.4 ± 0.2 ml, P > 0.05) or %H2O (81.3 ± 1.1 vs 80.0 ± 0.9, P > 0.05). However, compared to the vehicle group, the anti-CD18 group demonstrated a significant decrease in τ (162 ± 32 vs 64 ± 33 msec, P < 0.05) and CVR (184.8 ± 50.7 vs 64.6 ± 14.5 U/g, P < 0.05). These results demonstrate the attenuation of the low-reflow phenomenon and diastolic myocardial stunning by a monoclonal antibody which blocks PMN adhesion. We conclude that, despite successful 15-hr heart preservation with UW, myocardial performance remains limited by PMN-mediated reperfusion injury, which can be attenuated by blocking PMN adhesion molecule CD18 during reperfusion.
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