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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Induction of cyclic flow reduction in the coronary, carotid, and femoral arteries of conscious, chronically instrumented dogs. A model for investigating the role of platelets in severely constricted arteries.

Under sterile conditions, dogs were instrumented for continuous measurement of hemodynamics, and an Ameroid constrictor was positioned around either the left carotid, left femoral, or left anterior descending coronary artery to produce slowly progressive narrowing of the vessel. Cyclic flow reduction (CFR) developed in the carotid artery in seven of nine dogs on day 5.1 +/- 0.8 (mean +/- S.E.M.) at a frequency of 6.7 +/- 0.6 cycles per 30 min. This phenomenon was abolished for 30 +/- 5 and 45 +/- 15 min with intravenous administration of 50 and 100 micrograms/kg, respectively of the thromboxane receptor antagonist, BM 13.505, 4-[2-(4-chloro-benzene-sulfonamide)-ethyl]-benzene acetic acid. Total carotid artery occlusion occurred on day 7.9 +/- 0. 8. CFR developed in the femoral artery in one of three dogs on day 4 at a frequency of 7 cycles per 30 min and was abolished for 82 min after BM 13.505 (50 micrograms/kg i.v.). The vessel became totally occluded on day 7. Finally, CFR developed in the left anterior descending coronary artery in three of five dogs on day 9.3 +/- 4.9 at a frequency of 6.2 +/- 0.9 cycles per 30 min. CFR was abolished for 37 min after BM 13.505 (50 micrograms/kg i.v.) and for several hours after an oral dose of aspirin (650 mg). Total coronary occlusion was observed on day 17.4 +/- 2. 6. The present results demonstrate that CFR can be induced in various arteries in conscious, chronically instrumented dogs by slowly progressive narrowing via Ameroid constrictors. This phenomenon may serve as a model for transient ischemic attack, claudication, and unstable angina. Because the conscious state is maintained, drug interactions with anesthetics are avoided. The usefulness of inhibitors of platelet aggregation in this model documents the potential benefit of such compounds in various vascular disease states.[1]


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