Adjunctive therapy with low molecular weight heparin with recombinant tissue-type plasminogen activator causes sustained reflow in canine coronary thrombosis

Rethrombosis of the infarct-related artery after pharmacologic thrombolysis is a major limitation of the thrombolytic therapy. Platelet and fibrin deposition in the coronary artery after recombinant tissue-type plasminogen activator (rTPA) may play a leading role in reformation of thrombus. Therefore we examined the effect of low molecular weight heparin (LMWH) as adjunctive treatment with rTPA in a dog model of electrically induced intracoronary thrombus. Fourteen dogs, in which a stable coronary thrombus was induced with delivery of 100 μA of anodal direct current, were randomly given an intravenous bolus of LMWH, 75 IU/kg (n = 6), or saline (n = 8), followed by intravenous rTPA, 1 mg/kg over 20 minutes. LMWH (75 IU/kg) or saline was continuously infused over 90 minutes after rTPA-induced thrombolysis. Reperfusion occurred at 29 ± 7 minutes in six of eight dogs receiving rTPA plus saline (reperfusion rate 75%), while reperfusion occurred at 18 ± 3 minutes in all six dogs receiving rTPA plus LMWH (both p = NS versus rTPA plus saline group). Coronary reocclusion occurred in 83% of dogs given rTPA plus saline, but only in one dog (17%) given rTPA plus LMWH (p <0.05). Magnitude of reflow at 60 minutes of reperfusion was higher in the rTPA plus LMWH group than in the rTPA plus saline group (51 ± 14 ml/min versus 10 ± 9 ml/min; p <0.05). As expected, partial thromboplastin time was greater in rTPA plus LMWH than in rTPA plus saline-treated animals. Scanning electron microscopy (SEM) of coronary arteries showed a totally occlusive thrombus and intense platelet-fibrin deposition in dogs treated with rTPA plus saline. SEM showed a residual partially occlusive thrombus with qualitatively less platelet-fibrin deposition in dogs receiving rTPA plus LMWH. Thus adjunctive therapy with LMWH results in sustained reflow; however, the coronary artery continues to show residual thrombus and platelet-fibrin deposition.