An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis.

Coronary artery bypass grafts, angioplasty, and thrombolysis are beneficial procedures for patients with coronary artery disease. However, these procedures can fail by mechanisms related to interactions between platelets and the damaged arterial wall. An experimental model for studying some of the mechanisms of platelet interaction with endothelial- and medial-damaged stenosed arteries is described. Dogs or pigs are anesthetized, and the chest opened. The heart is exposed, the circumflex or left anterior descending coronary artery is dissected out, and an EMF or Doppler flow probe is placed on it. Distal to the flow probe, the artery is clamped with a vascular clamp to produce endothelial and/or medial injury. Then, an encircling plastic cylinder is placed around the outside of the injured artery, producing a "critical stenosis." Acute platelet thrombus formation begins to occur in the stenosed lumen, gradually increasing the amount of stenosis. This causes the coronary flow to decline and reach zero flow when the artery is completely occluded. Then, the thrombus is embolized into the distal circulation, and flow is restored to normal levels. This occurs repeatedly causing cyclic flow reductions (CFRs). These CFRs can be made larger and to occur more frequently by increasing in vivo platelet activity, by raising the plasma catecholamine levels, or by increasing the collagen exposed in the stenosed lumen by increased medial damage. If an effective dose of an antiplatelet agent is given, the CFRs will be decreased in size and frequency or abolished entirely. Aspirin and other agents abolish the CFRs in this model; however, CFRs can be renewed by infusions of catecholamines or platelet activating factor. Thus, the model may be useful for studying mechanisms that enhance or inhibit arterial thrombosis in stenosed arteries with endothelial and medial injury.