Pc. Kouretas et al., HEPARIN AND NONANTICOAGULANT HEPARIN PRESERVE REGIONAL MYOCARDIAL-CONTRACTILITY AFTER ISCHEMIA-REPERFUSION INJURY - ROLE OF NITRIC-OXIDE, Journal of thoracic and cardiovascular surgery, 115(2), 1998, pp. 440-448
Objectives: These studies were performed to determine the effect of he
parin and nonanticoagulant heparin on myocardial function after ischem
ia-reperfusion and to further evaluate the role that the nitric oxide-
cyclic guanosine monophosphate pathway plays in mediating the effect o
f heparin. Methods: Fifteen dogs were subjected to 15 minutes ischemia
followed by 120 minutes reperfusion and pretreated with either saline
solution, bovine heparin (6.0 mg/kg intravenously), or N-acetyl hepar
in (6.0 mg/kg intravenously), a heparin derivative without anticoagula
nt properties. The left anterior descending artery was occluded for 15
minutes and regional systolic shortening, a unitless measure of myoca
rdial contractility, assessed during reperfusion, To evaluate the role
of nitric oxide, the inhibitor N-omega-nitro-L-arginine, 1.5 mg/kg in
tracoronary, was given before heparin administration, Myocardial level
s of cyclic guanosine monophosphate, the second messenger of nitric ox
ide, were also measured in the N-acetyl heparin group using radioimmun
oassay. Results: Regional systolic shortening was significantly decrea
sed in the saline group during 60 and 120 minutes compared with before
ischemia (9.2 +/- 1.0 and 9.0 +/- 0.9 vs 12.2 +/- 1.2, p less than or
equal to 0.0003), Heparin and N-acetyl heparin-treated dogs, however,
showed preservation of systolic shortening throughout reperfusion, Ad
ministration of nitro-L-arginine significantly attenuated the protecti
ve effect of heparin (9.2 +/- 1.2 vs 12.7 +/- 1.1, p less than or equa
l to 0.0001) and N-acetyl heparin (9.3 +/- 0.3 vs 12.8 +/- 0.1, p less
than or equal to 0.0001) during 120 minutes reperfusion. Myocardial l
evels of cyclic guanosine monophosphate were also significantly increa
sed in the N-acetyl heparin group compared with saline (199.1 +/- 7.1
vs 103.5 +/- 4.5 pmol/mg, p less than or equal to 0.0001). Conclusions
: Heparin preserves myocardial contractility after ischemia-reperfusio
n independent of its anticoagulant properties. Furthermore, the protec
tive effects of heparin during ischemia-reperfusion are mediated, at l
east in part, through a nitric oxide-cyclic guanosine monophosphate pa
thway.