Beneficial effect of nitroglycerin on arterial rethrombosis after thrombolysis: Results from a rabbit thrombosis model

Background: Although nitroglycerin (NTG) is commonly administered to patients with acute myocardial infarction, its effect on concomitant thrombolytic 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 produced in a rabbit femoral artery with endothelial damage and distal stenosis. 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 continuously for 2 h. Fourteen rabbits were randomized into two groups (group 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 μg. kg^-1. min^-1 for 130 min. Reperfusion at the end of the 120 min 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 in the remaining two rabbits. These flow patterns were not observed in any of group B rabbits. Overall patency duration was significantly prolonged 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 boluses 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 groups. However, NTG infusion was associated with increased restored femoral flow following recanalization (expressed as % of stenotic flow value over observation time) compared to control group (P=0·025 by repeated measures ANOVA). Conclusion: Adding NTG to a thrombolytic regimen with rt-PA, aspirin and heparin increases the magnitude of restored flow and total patency duration following recanalization in a rabbit model of arterial thrombosis.