[Thrombosis and ischemia: experimental data].
Thrombosis and ischaemia are often linked to an atherosclerotic arterial lesion. An inflammatory process implicating leucocytes and inflammation mediators (cytokines) as well as atheroma plaque rupture liberating tissue factor are at the origin of this pathology. Equally, blood platelets play an important role, not only with the formation of platelet aggregates, but also by their procoagulant action resulting from the exposure of membrane phospholipids. Apoptotic cells release procoagulant microparticles from the plaque, favouring thrombogenesis. In this context reperfusion would a priori restore blood flow, but it is also the origin of cytotoxicity due to the sudden release of necrotising factors. Various animal models are used to experimentally reproduce arterial thrombosis either following or not following ischaemia/reperfusion. Among them the model of progressive coronary occlusion by intraluminal electrical stimulation, the model of quasi-instantaneous thrombosis by the introduction of a copper coil, and the model of ischaemia/reperfusion by occlusion of the left descending coronary for 90 minutes followed by reperfusion have been studied more precisely in the dog. In the rat, cerebral ischaemia followed by reperfusion has been provoked with occlusion of the middle cerebral artery. The studies in dogs show that Enoxaparine significantly reduces the formation of coronary thrombus induced progressively by an anodal current and potentiates the action of the tissular activator plasminogen (t-PA) on a recently formed thrombus. At the level of myocardial ischaemia. Enoxaparine reduces the extent of infarction as well as the neutrophil and platelet accumulation in the infarcted zone or in at risk zone. This effect seems to correlate with an anti-inflammatory type action demonstrated elsewhere in vitro with platelet/neutrophil adhesion in the presence of P-Selectin. In all of these studies standard heparin used under the same conditions proves to be inactive. In the ischaemia/reperfusion model in the dog, aspirin has been shown to be ineffective up to a dose of 6 mg/Kg. Enoxaparine is an example of a possible double anti-thrombotic and anti-ischaemic component in the prevention of disorders caused by the thrombosis-ischaemia-reperfusion triad.
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Laboratoire Aventis-Pharma, 13, Quai Jules Guesde, 94403 Vitry-sur-Seine.
D000818:Animals; D017209:Apoptosis; D003328:Coronary Thrombosis / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D017984:Enoxaparin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology*; D012307:Risk Factors
D017984:Enoxaparin; D005343:Fibrinolytic Agents