Effects of a monoclonal antibody to P-selectin on recovery of neonatal lamb hearts after cold cardioplegic ischemia.
BACKGROUND
The interaction between endothelium and leukocytes plays a crucial role in ischemia-reperfusion injury. P-selectin, which is expressed on activated endothelium, mediates the first step in leukocyte adherence to the endothelium. This study examined the effects of a monoclonal antibody (mAb) against P-selectin on the recovery of cardiac function and myocardial neutrophil infiltration after ischemia.


RESULTS
Thirteen blood-perfused, isolated neonatal lamb hearts underwent 2 hours of hypothermic cardioplegic arrest and 2 hours of reperfusion. Immediately before reperfusion, mAb to P-selectin was administered to the perfusate (15 micrograms/mL) in 6 hearts (group P-sel). In control (n = 7), the same volume of saline was added. Isovolumic left ventricular function and coronary blood flow were measured. At 2 hours after reperfusion, myocardial myeloperoxidase activity, an index of neutrophil accumulation, was assayed. At 30 minutes of reperfusion, hearts treated with mAb to P-selectin achieved significantly greater recovery of maximum developed pressure (70 +/- 4% in control versus 77 +/- 2% in group P-sel, P < 0.01), maximum positive first derivative of pressure (dP/dt) (64 +/- 7% in control versus 73 +/- 5% in group P-sel, P < 0.05), and maximum negative dP/dt (61 +/- 6% in control versus 70 +/- 6% in group P-sel, P < 0.05) compared with control. Percent baseline of coronary blood flow was also significantly increased in group P-sel (135 +/- 40% in control versus 205 +/- 43% in group P-sel, P < 0.05). Myocardial myeloperoxidase activity was significantly lower (P < 0.05) in group P-sel (4.7 +/- 3.2) versus control (16.0 +/- 10.1). (Units are change in absorbance/min/g tissue.)


CONCLUSIONS
The functional blockade of P-selectin resulted in better recovery of cardiac function and attenuated neutrophil accumulation during early reperfusion. Strategies to block P-selectin mediated neutrophil adherence may have clinical application in improving myocardial function at early reperfusion.
Nagashima
M
M
Department of Cardiovascular Surgery, Children's Hospital, Boston, MA 02115, USA.
Shin'oka
T
T
Nollert
G
G
Shum-Tim
D
D
Hickey
P R
PR
Roth
S J
SJ
Kirchhoff
A
A
Springer
T A
TA
Burke
P R
PR
Mayer
J E
JE
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D003080:Cold Temperature; D003326:Coronary Circulation / Q000502:physiology; D006321:Heart / Q000503:physiopathology*; D006324:Heart Arrest, Induced; D007958:Leukocyte Count; D008054:Lipid Peroxides / Q000378:metabolism; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D019007:P-Selectin / Q000276:immunology / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010976:Platelet Count; D012756:Sheep; D014655:Vascular Resistance / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D000911:Antibodies, Monoclonal; D008054:Lipid Peroxides; D019007:P-Selectin; D009195:Peroxidase