Folts-model

Demrow et al. (1995) used the Folts model of unstable coronary stenosis, which closely mimics ruptured atherosclerotic plaque, causing unstable angina, to examine the effects of grape juice on platelet function in vivo. In this model,... 

Thrombosis (Folts-Model) 277 I.M.4.2 Arterial Bleeding Time... 

Stenosis- and Mechanical Injury-Induced Coronary Thrombosis (Folts-Model)... 

Fig. 4. Technique for monitoring platelet aggregation in the partially obstructed left circumflex coronary artery of the dog. Electromagnetic flow probes measure blood flow. Partial obstruction of the coronary artery with a plastic Lexan cylinder results in episodic cyclical reductions in coronary blood flow that are due to platelet-dependent thrombus formation. Every 2-3 mm the thrombus must be mechanically shaken loose to restore blood. For detailed application of the Folts model, see Sullivan et al. (1992) Folts, Rowe (1974, 1988) and Folts et al. (1976, 1982).

The clinical relevance of studies in the Folts-model has been questioned because the model is very sensitive to antithrombotic compounds. However, the lack of a reversal of the effect by epinephrine or increase in degree of stenosis differentiates any new drug from aspirin. Electrical coronary thrombosis is less sensitive e.g. aspirin has no effect and with some drugs higher dose levels are required but in principle, most drug mechanisms act in both models if at all. 

In conclusion, the Folts model of cyclic coronary blood flow variations clearly involves platelet microembolization. However, the role of physical obstruction versus microvascular constriction in the impaired myocardial perfusion is not entirely clear. Platelet-endothelium and platelet-leukocyte interactions may also contribute to the local inflammatory response37. 

Folts model artery stenosis and intimal damage [40], produced by vessel clamping causing exposure of sub-endothelial collagen and tissue factor Platelet rich Cyclic variations in arterial blood flow caused by repeated thrombus formation and embolisation Efficacy of antithrombotic agents... 

In the Folts model, tirofiban (0.3mg/kg i.v.) gave 85% inhibition of ADP or collagen induced platelet aggregation, and abolished cyclic flow variations in the canine left circumflex coronary artery, with a short duration of action (18min). In the electrically induced thrombosis model, an infusion of tirofiban (10 g/kg/min), which produced 90% inhibition of platelet aggregation ex vivo, delayed or fully prevented occlusive thrombosis in the canine left circumflex coronary artery [145],... 

In order to study new drugs for their antithrombotic potential in coronary arteries, Folts and Rowe (1974) developed the model of periodic acute platelet thrombosis and cyclic flow reductions (CFRs) in stenosed... 

Folts JD (1991) An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. Circulation 83 (Suppl IV) IV-3-IV-14... 

Romson JL, Haack DW, Lucchesi BR (1980b) Electrical induction of coronary artery thrombosis in the ambulatory canine a model for in vivo evaluation of anti-thrombotic agents. Thromb Res 17 841-853 Ruebsamen K, Kirchengast M (1998) Thrombin inhibition and intracoronary thrombus formation effect of polyethylene glycol-coupled hirudin in the stenosed, locally injured canine coronary artery. Coron Artery Dis 9 35-42 Sullivan J, Hansen P, Rahko PS, Folts JD (1992) Continous measurement of left ventricular performance during and after maximal isometric deadlift exercise. Circulation 85 1406-1413... 

Coller BS, Folts JD, Scudder LE, Smith SR (1986) Antithrombotic effect of a monoclonal antibody to the platelet glycoprotein Ilb/IIIa receptor in an experimental animal model. Blood 68 783-786... 

Cyclic coronary blood flow variations, such as seen in the Folts experimental model (see above), are observed during coronary interventions85 87 and are a sign predicting immediate complications in patients who underwent angiographically successful percutaneous transluminal coronary angioplasty.88... 

Lamifiban (lmg/kg infused over 20 min) [146] abolished cyclic flow variations in a Folts type model using the guinea pig carotid artery. This model is thought to be of relevance to transient ischaemic attacks and cerebral infarction aspirin, heparin or hirudin were only partially effective [146],... 

The ester prodrug S5740 (O.lmg/kg i.d.) prevents thrombus formation (94% reduction in cyclic flow variations) in a Folts type model of coronary thrombosis in the dog [132,152],... 

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