An antibody to leukocyte integrins attenuates coronary vascular
injury in a canine model of ischemia and reperfusion.
Horwitz, Lawrence D., Dimitri Kaufman, and Yinong Kong.
Division of Cardiology, University of Colorado Health Sciences
Center, Denver CO 80262
APStracts 3:0332H, 1996.
Background. Ischemia and reperfusion causes coronary vascular and
myocardial injury, which may be due to leukocyte-mediated processes.
Anti-leukocyte measures have reduced injury after brief reperfusion
periods of 1-3 hours but there has been little information on whether
benefits are apparent after longer periods of reperfusion. Methods
and Results. We examined the effect of pretreatment with a monoclonal
antibody (R15.7) to the CD18 family of leukocyte adhesion molecules (
2 integrins) in dogs exposed to regional coronary ischemia for 1 hour
of left anterior descending coronary artery ligation and then
reperfused for 48 hours. Coronary microvascular permeability was
assessed in vivo by measurement of protein leak index (PLI), using a
double isotope technique with autologous radiolabeled transferrin and
erythrocytes. Vasorelaxation was measured in vitro with
preconstricted epicardial coronary artery rings subjected to
increasing concentrations of the endothelium-dependent vasodilators
bradykinin (BK) and adenosine diphosphate (ADP), and the endothelium
-independent vasodilator nitroprusside. At 48 hours of reperfusion in
untreated dogs there were substantial increases in PLI in the
previously ischemic regions, indicative of increased extravascular
transferrin. These abnormalities were decreased, but not abolished,
in the dogs treated with R15.7. Relaxation of rings from the
ischemic/reperfused artery to BK and ADP were blunted in the
untreated dogs. R15.7 resulted in improvement in some, but not all,
indices of relaxation in response to BK and ADP. Relaxation to
nitroprusside was normal in ischemic/reperfused coronary rings from
both treated and untreated dogs. Conclusions. Therefore, following 1
hour of regional coronary ischemia and 48 hours of reperfusion,
coronary endothelial injury, which was manifested by increased
coronary microvascular permeability and abnormalities in coronary
endothelium-dependent relaxation, was reduced by pretreatment with
the anti-CD18 integrin antibody R15.7.
Received 14 December 1995; accepted in final form 10 July 1996.
APS Manuscript Number H1171-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 21 August 1996