BENEFICIAL EFFECT OF NITROGLYCERIN ON ARTERIAL RETHROMBOSIS AFTER THROMBOLYSIS - RESULTS FROM A RABBIT THROMBOSIS MODEL

Background: Although nitroglycerin (NTG) is commonly administered to p atients with acute myocardial infarction, its effect on concomitant th rombolytic therapy has not been fully elucidated. We examined whether NTG administration further optimizes thrombolysis with rt-PA, combined with aspirin and heparin. Methods and Results: Blood clots were produ ced in a rabbit femoral artery with endothelial damage and distal sten osis. rt-PA was administered in repeated bolus i.v. injections of 0.3 mg. kg-1 every 10 min for 50 min. Femoral artery flow was measured con tinuously for 2 h. Fourteen rabbits were randomized into two groups (g roup A and B), both receiving aspirin (i.v. 17 mg.kg-1) and heparin (i .v. 200 units. kg-1) prior to the first rt-PA bolus injection. NTG was administered in group B only, 10 min prior to the first rt-PA bolus, at 10 mug.kg-1.min-1 for 130 min. Reperfusion at the end of the 120 mi n observation period occurred in 5/7 group A and 6/7 group B rabbits ( P=ns). In 3/7 group A rabbits, re-flow was achieved but persistent re- occlusion subsequently developed in 1/3 and oscillatory re-flow and re -occlusion cycles (cyclic re-flow) with subsequent patency developed i n the remaining two rabbits. These flow patterns were not observed in any of group B rabbits. Overall patency duration was significantly pro longed with NTG (group B; 578/840 min) compared to controls (group A; 258/840 min) (P<0.001). The mean recanalization time (group A; 30.8 +/ - 9.3 vs group B; 22.5 +/- 4.7 min, P=0.16) as well as mean rt-PA bolu ses needed to achieve complete recanalization (group A; 4.3 +/- 0.7 vs group B; 3.3 +/- 0.6 boluses/rabbit, P=0.3) did not differ between gr oups. However, NTG infusion was associated with increased restored fem oral flow following recanalization (expressed as % of stenotic flow va lue over observation time) compared to control group (P= 0.025 by repe ated measures ANOVA). Conclusion: Adding NTG to a thrombolytic regimen with rt-PA, aspirin and heparin increases the magnitude of restored f low and total patency duration following recanalization in a rabbit mo del of arterial thrombosis.