Prevention of CD18-mediated reperfusion injury enhances the efficacy of UW solution for 15-hr heart preservation.
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 degrees C UW. After insertion of an left ventricular (LV) balloon, hearts were heterotopically transplanted into recipients pretreated with either intravenous (i.v.) saline (vehicle, n = 8) or i.v. 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 (beta), the volume-axis intercept (Vo) of the end-diastolic P-V relation, and the time constant of the exponential LV pressure decay after dP/dt min (tau) 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), beta (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).(ABSTRACT TRUNCATED AT 250 WORDS)
Byrne
J G
JG
Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115.
Murphy
M P
MP
Smith
W J
WJ
Couper
G S
GS
Appleyard
R F
RF
Cohn
L H
LH
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018821:CD18 Antigens; D005978:Glutathione / Q000494:pharmacology; D016027:Heart Transplantation; D007328:Insulin / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009504:Neutrophils / Q000502:physiology; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011817:Rabbits; D011887:Raffinose / Q000494:pharmacology
D015703:Antigens, CD; D018821:CD18 Antigens; D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D000255:Adenosine Triphosphate; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose