Circulation, Vol 83, 2122-2127, Copyright © 1991 by American Heart Association
JD Folts, J Stamler and J Loscalzo
BACKGROUND. Nitroglycerin and other clinically relevant organic nitrate
derivatives have been shown to inhibit platelet aggregation in vitro. This
antithrombotic effect of nitrates is potentiated by reduced thiol. To
determine the potential relevance of this mechanism of action in vivo, we
examined the effect of intravenous nitroglycerin infusion on periodic
platelet thrombus formation in a canine model of coronary artery stenosis.
METHODS AND RESULTS. We used a canine model of coronary artery stenosis
associated with cyclic reductions in coronary blood flow that have been
shown to depend on periodic platelet thrombus formation. We quantified the
frequency of cycles per 40-minute observation period and monitored the
effect of a continuous infusion of intravenous nitroglycerin on the cycle
frequency. The administration of 10-15 micrograms/kg/min nitroglycerin
reduced cyclic platelet thrombus formation significantly and did so without
a significant change in coronary artery blood flow. Pretreatment with the
reduced thiol, N- acetylcysteine (100 mg/kg during 30 minutes), led to
inhibition of cyclic platelet thrombus formation by intravenous
nitroglycerin at doses that alone had no such effect (5 micrograms/kg/min).
CONCLUSION. These data suggest that one mechanism by which intravenous
nitroglycerin improves ischemia in acute coronary artery disease syndromes
may be by inhibition of platelet thrombus formation and may highlight the
potential importance of reduced thiol in this mechanism.
ARTICLES
Intravenous nitroglycerin infusion inhibits cyclic blood flow responses caused by periodic platelet thrombus formation in stenosed canine coronary arteries
Department of Medicine, University of Wisconsin Medical School, Madison 53792.
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