D. Libersan et al., THE LOW-MOLECULAR-WEIGHT HEPARIN, ENOXAPARIN, LIMITS INFARCT SIZE AT REPERFUSION IN THE DOG, Cardiovascular Research, 37(3), 1998, pp. 656-666
Objective: Heparin (HEP) is used in the post-thrombolytic state to pre
vent vessel reocclusion, thereby aiding myocardial salvage. Side effec
ts limit its benefits, but besides anticoagulant activity HEP has diff
use actions that may be potentially beneficial to jeopardized reperfus
ed myocardium. This study compares the effect of therapeutic doses of
HEP and enoxaparin (ENOX), a low molecular weight heparin, and to stre
ptokinase (SK), on infarct size. Methods: The left anterior descending
coronary artery was occluded in dogs for 90 min, followed by 6 h of r
eperfusion with a residual critical stenosis in place. Five min before
reperfusion, HEP (2800 IU) was injected i.v., and perfused at 500 IU/
h until sacrifice in group 2, while groups 3 and 4 received ENOX (2128
anti-Xa IU i.v.) followed by 380 anti-Xa IU/h. Group 4 was also given
500000 IU SK over 30 min before reperfusion beginning at 55 min of oc
clusion (ENOX + SK), while group 5 received only SK. Controls (CON, gr
oup I) received saline. P-selectin mediated platelet-neutrophil rosett
es formation was also tested in vitro in the presence of HEP and ENOX.
Results: The area at risk delimited by dye perfusion was statisticall
y similar among groups. Covariance analysis between infarct size (% of
area at risk) delimited with triphenyltetrazolium and collateral flow
measured with radioactive microspheres confirmed that groups given EN
OX (21.6 +/- 5.5%) and ENOX + SK (24.9 +/- 3.9%) developed smaller inf
arcts (P < 0.05) than CON (48.1 +/- 4.5%), as opposed to HEP (32.2 +/-
3.6%) and SK (46.8 +/- 3.4%) groups. In-111-platelet counts in the in
farct were reduced significantly by 64% in the ENOX group as compared
to CON, and to a lesser extent (42%, n.s.) in the ENOX + SK group, but
were not reduced by HEP and SK treatments. Neutrophil accumulation in
the infarcts was decreased significantly and by more than 75% in the
ENOX and ENOX + SK groups versus CON, but not in the HEP and SK groups
. Also, only ENOX (10-100 mu g/ml) significantly inhibited platelet-ne
utrophil rosettes formation in a plasmatic milieu. Conclusions: The EN
OX treatment, as opposed to that of HEP, reduces myocardial platelet a
nd neutrophil accumulations, and limits infarct size when given just b
efore and during reperfusion. The benefits of ENOX on infarct size wer
e not modified by SK, and may be related, at least in part, to an inte
raction with P-selectin-mediated cell adhesion. (C) 1998 Elsevier Scie
nce B.V.