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 microA 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 less than 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 less than 0.05). As expected, partial thromboplastin time was greater in rTPA plus LMWH than in rTPA plus saline-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Nicolini
F A
FA
Department of Medicine, University of Florida, College of Medicine, Gainesville 32610-0277.
Nichols
W W
WW
Saldeen
T G
TG
Khan
S
S
Mehta
J L
JL
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels / Q000648:ultrastructure; D004285:Dogs; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D008855:Microscopy, Electron, Scanning; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D006495:Heparin, Low-Molecular-Weight; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator