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Homeister J. W. BS; Mickelson, J. K. MD; Hoff, P. T. MS; Lucchesi, B. R. MD, PhD
Coronary Artery Disease: April 1991
LABORATORY INVESTIGATION: PDF Only
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Recombinant desulphatohirudin HV1 (r-hirudin), a specific and potent inhibitor of thrombin. was tested for its ability to prevent experimentally induced coronary artery thrombosis. Anesthetized, open chest dogs were administered 111In-labeled autologous platelets and treated with r-hirudin (5 mg/kg bolus+ 2 mg/kg/h as an intravenous infusion, n = 11) or saline (control, n = 11). Intimal injury to the left circumflex coronary artery was produced with an anodal direct current (100 μA) applied for 5 hours, or until 30 minutes after thrombosis, whichever occurred first. Administration of r-hirudin increased the prothrombin time 1.5 to 2-fold and the partial thromboplastin time 2.5-fold (P<0.05). Coronary artery blood flow decreased to 0 mL/min in each of the control dogs, and in 5 of the 11 r-hirudin-treated dogs. In the remaining 6 r-hirudin-treated dogs, the coronary artery blood flow at the end of the protocol (31±2 mL/min) was reduced slightly from the baseline value (34±3 mUmin). r-Hirudin decreased the incidence of thrombosis (P<0.02) and increased the mean time required for thrombotic occlusion to occur (control, 101±14 mm [n= 11]; r-hirudin, 237±8 min [n = 5]; P<0.0001). Thrombus weight was decreased by the r-hirudin treatment (control, 10.4±1.1 mg; r-hirudin 4.5±0.8 mg; P<0 05). but the number of platelets incorporated per milligram of thrombus was similar in both groups. Ex vivo platelet aggregation induced by arachidonic acid or collagen was not affected by r-hirudin administration. In washed-platelet preparations, thrombin-induced (0.1 U/mL) platelet aggregation was inhibited in a dose-dependent manner by the addition of r-hirudin with complete inhibition obtained at 175 ng/mL r-Hirudin was effective in delaying, and reducing the incidence of, coronary artery thrombosis in this experimental model

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