Abstract | OBJECTIVES: We sought to evaluate whether anticoagulation by an intravenous heparin infusion prevents deterioration of coronary blood flow restored by the novel recombinant plasminogen activator BM 06.022, and to compare the effects of profound fibrinogenolysis with those of an intravenous bolus injection of heparin. BACKGROUND: METHODS:
BM 06.022 is an unglycosylated variant of human tissue-type plasminogen activator. Thrombus formation in anesthetized open chest dogs was induced by electrical injury. Left circumflex coronary artery blood flow was monitored for 4 h using an electromagnetic flow probe. Twenty dogs were randomized to receive intravenous heparin (100 IU/kg bolus plus 100 IU/kg per h) in group B or saline solution in group A before an intravenous bolus injection of 200 kU/kg (= 0.34 mg/kg) BM 06.022 1 h after thrombus formation. Another 14 dogs were randomized to receive a single intravenous bolus injection of 200 IU/kg heparin plus 200 kU/kg BM 06.022 in group D or saline solution plus 1,000 kU/kg BM 06.022 in group C. RESULTS: In the absence of a systemic lytic state, heparin infusion prolonged (p < 0.05) the cumulative patency time (sum of time intervals during which the coronary artery was patent) to 204.3 +/- 7.4 min (group B) compared with 34.6 +/- 10.8 min with saline solution (group A), and increased (p < 0.05) the area under the curve for coronary blood flow versus time (AUCFlow) to 34.0 +/- 3.4 ml.h.min-1 compared with 7.7 +/- 4.6 ml.h.min-1. Profound fibrinogenolysis after administration of 1,000 kU/kg BM 06.022 (group C) and a single intravenous heparin injection (group D) did not differ in their effects on the cumulative patency time (182 +/- 30.3 vs. 177.5 +/- 25.4 min) and AUCFlow (36.0 +/- 10.3 vs. 30.5 +/- 4.8 ml.h.min-1), but these values were improved (p < 0.05) compared with those obtained after administration of saline solution plus 200 kU/kg BM 06.022 (group A). CONCLUSIONS: In the absence of a systemic lytic state, intravenous heparin is required as an adjunct to BM 06.022 to maintain coronary blood flow in dogs.
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Authors | U Martin, S Fischer, G Sponer |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 22
Issue 3
Pg. 914-20
(Sep 1993)
ISSN: 0735-1097 [Print] United States |
PMID | 8354832
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Fibrinolytic Agents
- Recombinant Proteins
- Heparin
- reteplase
- Tissue Plasminogen Activator
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Topics |
- Analysis of Variance
- Animals
- Coronary Circulation
(drug effects)
- Coronary Thrombosis
(blood, drug therapy, epidemiology, physiopathology)
- Disease Models, Animal
- Dogs
- Drug Evaluation, Preclinical
- Drug Therapy, Combination
- Female
- Fibrinolytic Agents
(therapeutic use)
- Heparin
(therapeutic use)
- Male
- Random Allocation
- Recombinant Proteins
(therapeutic use)
- Thrombolytic Therapy
- Tissue Plasminogen Activator
(therapeutic use)
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