Nitroglycerin inhibits experimental thrombosis and reocclusion after thrombolysis.
Nitroglycerin inhibits platelet aggregation in vitro, but its effect on thrombosis and platelet function in vivo is controversial. This study assessed the effect of nitroglycerin on primary thrombus formation in response to vessel wall injury and secondary thrombus formation, or rethrombosis, after lysis of an existing thrombus. In the first protocol the right carotid artery was instrumented with a flow probe, stenosis, an anodal electrode, and a proximal infusion line. A 300 microA anodal current was used to induce endothelial injury and subsequent thrombotic occlusion of the vessel. Anisoylated plasminogen streptokinase activator complex (APSAC; 0.05 U/kg intraarterially) was injected proximal to the thrombus 30 minutes after occlusion. After APSAC, nitroglycerin (1 microgram/kg/min intraarterially, n = 7) or vehicle (n = 6) was infused proximal to the thrombus for 3 hours. Reocclusion occurred in two of seven nitroglycerin-treated dogs and six of six vehicle-treated dogs (p < 0.05). In the second protocol both carotid arteries were instrumented as described previously. Anodal current (300 microA, 180 minutes) was applied to the right carotid (n = 12) artery to determine control times to occlusion. The left carotid artery served as the test vessel, receiving either nitroglycerin (1 microgram/kg/min intraarterially, n = 6) or trimethaphan (0.05 mg/kg/hr intraarterially, n = 6). Trimethaphan was used to produce controlled hypotension to match the approximately 10% decrease in mean arterial blood pressure that was observed during nitroglycerin infusion. Control arteries and those treated with trimethaphan formed occlusive thrombi in all instances. Nitroglycerin infusion resulted in a lower incidence of occlusion (1 of 6; p < 0.05 vs control value) and inhibited ex vivo platelet aggregation to adenosine diphosphate and arachidonic acid (p < 0.05). Local infusion of nitroglycerin reduced the formation of primary thrombi, independent of the hypotensive effect of the drug, and exerted systemic effects on platelet aggregation. Furthermore, platelet inhibition with nitroglycerin reduced the incidence of secondary thrombus formation (rethrombosis) after thrombolysis. The results suggest that a potential benefit of nitroglycerin therapy may be derived from its ability to inhibit thrombotic events in patients with unstable angina or myocardial infarction.
Werns
S W
SW
Division of Cardiology, University of Michigan Medical Center, University Hospital, Ann Arbor 48109-0022.
Rote
W E
WE
Davis
J H
JH
Guevara
T
T
Lucchesi
B R
BR
D000818:Animals; D016255:Anistreplase / Q000627:therapeutic use*; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000502:physiology; D002985:Clinical Protocols; D004285:Dogs; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology / Q000627:therapeutic use*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012008:Recurrence; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control*
D010975:Platelet Aggregation Inhibitors; D016255:Anistreplase; D005996:Nitroglycerin