Animal models thrombosis

Since the early 1980s, much effort has focused on animal models of acute and chronic neurodegeneration in search of therapeutics for stroke. Neuronal cell death follows strokes, acute ischemic insults, and chronic neurodegeneration, such as Parkinson s disease, Alzheimer s disease (AD), epilepsy, and Huntington s disease. Up to 80% of all strokes result from focal infarcts and ischemia in the middle cerebral artery (MCA), so the commonly used animal models for neuroprotection are produced by temporary or permanent occlusion of the MCA.5 Lesions of the MCA include occlusion by electrocoagulation, intraluminal monofilaments, photochemical effects, thrombosis, and endothelin-1, but all of these models necessitate studying reperfusion events and validating MCA occlusion by behavioral assessments. 

TFPI, when administered to rabbits, has been shown to have an antithrombotic effect when thromboplastin was used as a thrombogenic challenge (I 10). TFPI was also shown to be an effective inhibitor when thrombosis was induced in rabbit jugular veins by endothelial destruction and restricted blood flow. The antithrombotic and antiprotease actions of TFPI have been tested in several other animal models. Warn-Cramer et al. investigated the effect of immunodepletion of TFPI in factor Vila and Xa induced coagulation in rabbits (III). These rabbits were observed to be sensitized to the procoagulant effects of factor Vila, but not factor Xa in the absence of factor Vila. Two studies have indicated that TFPI administration reduces the lethal effects of . coli administration in a septic shock model in baboons (I 12). These studies also indicated that TFPI may have an anti-inflammatory effect, as an attenuation of the IL-6 response was also observed. Administration of TFPI has been observed to prevent... 

As low levels of protein C activation peptide are found in healthy individuals, it is suggested that protein C is constantly activated to a small degree (124). Protein C administration has been shown to inhibit both arterial and venous thrombosis in animal models (125). Heterozygous protein C deficiency or activated protein C resistance due to factor V mutation is thought to explain 60% to 70% of the cases of familial thrombophilia (I 16). 

Elevated TAFI levels have been found in men with symptomatic coronary artery disease (142). TAFI is also reported to be a risk factor for deep venous thrombosis, A recent report on the high levels of TAFI in the acute phase of ischemic stroke revealed not only elevated levels but also an incremental increase in TAFI with the degree of neurologic deterioration (143). Therefore, the observation by Boffa et al. on the acute phase nature of this protein requires further validation, In addition, Juhan-Vague et al, stated that there is a correlation between TAFI levels and cardiovascular risk factors (144). Animal models may be needed to truly validate studies on TAFI upregulation and its relation to thrombosis. 

Ischemia results from an imbalance of oxygen supply and demand. In patients with ACS, multiple studies of atheroma have implicated inflammation as a critical part of the syndrome. Signs of inflammation in animal models and humans occur with lipid accumulation in the artery wall and plaque development. Plaque rupture and thrombosis have abruptly narrowed or occluded the coronary arteries precipitating ACS (14). 

In most animal models of thrombosis, healthy animals are challenged with thrombogenic (pathophysiologic) stimuli and/or physical stimuli to produce thrombotic or occlusive conditions. These models are useful for the screening of antithrombotic drugs. 

Each setting in the design of an animal model can answer specific question in relation to certain thrombotic disorders in human. However, the ultimate model of human thrombosis is in humans. 

Herrmann KS (1983) Platelet aggregation induced in the hamster cheek pouch by a photochemical process with excited fluorescein isothiocyanate-dextran. Micovasc Res 26 238-249 Just M, Tripier D, Seiffge D (1991b) Antithrombotic effects of recombinant hirudin in different animal models. Haemostasis 21 (Suppl l) 80-87 Matsuno H, Uematsu T, Nagashima S, Nakashima M (1991) Photochemically induced thrombosis model in rat femoral artery and evaluation of effects of heparin and tissue-type plasminogen activator with use of this model. J Pharmacol Methods 25 303-317... 

The presence of foreign materials in the circulation produces activation of the coagulation and the platelet system. Various prothrombotic surfaces have been used to develop experimental animal models. In contrast to many other thrombosis models, the thrombosis induced by foreign surfaces does not presuppose endothelial damage. 

Table 10 Animal models of thrombosis and their clinical correlates.

Table 2.3. ANIMAL MODELS OF ARTERIAL THROMBOSIS AND THROMBOLYSIS... 

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