Electrical-Induced Thrombosis

The use of electrical current to induce thrombosis in hamster and dog has been described in the early 1950s by Lutz et al. (1951) and Sawyer and Pate (1953a,b). In general, two different approaches exist. One method produces electrical damage by means of two externally applied hook-like electrodes (Hladovec 1973 Philp et al. 1978). The other method uses a needle electrode which is advanced through the walls of the blood vessels and positioned in their lumen the second electrode is placed into a subcutaneous site completing the circuit (Salazar 1961 Romson et al. 1980 Benedict etal. 1986). 

Anaesthetized rats weighing 200-300 g are intubated and a femoral artery is cannulated for administration of drugs. One carotid artery is isolated from surrounding tissues over a distance of 10-15 mm. 

A pair of rigid stainless-steel wire hook-like electrodes with a distance of 4 mm are adjusted to the artery by means of a rack and pinion gear manipulator. The artery is raised slightly away from the surrounding tissue. Isolation of the electrodes is achieved by the insertion of a small piece of parafilm under the artery. Blood flow is measured with an ultrasonic Doppler flowmeter (Transonic, Ithaca NY, USA) the flow probe (1RB) is placed proximal to the damaged area. 

Blood flow before and after induction of thrombus for 60 min 

Time to occlusion (min) the time between onset of the electrical current and the time at which blood flow decreases under 0.3 ml/min 

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Electrically induced thrombosis [41], [42], [43] electrode placed directly into a coronary artery causing endothelial disruption Platelet rich, but significant fibrin/ red cell content Coronary artery blood flow (e.g. electromagnetic flow probe) Efficacy of antithrombotic agents adjunctive agents in thrombolysis... 

In contrast to the efficacy of abciximab in the electrically induced thrombosis model and in stent thrombosis (see above), aspirin and heparin, or combinations of the two, were ineffective in these models. However, in the electrically induced thrombosis model in the dog, combination of 7E3... 

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],... 

The following parameters are determined to quantify electrically induced coronary thrombosis ... 

In order to compare the effects of 7E3F(ab )2 on arterial versus venous thrombolysis, a canine model was employed in which thrombosis was electrically induced simultaneously in the carotid artery and jugular vein [159], Whilst 7E3F(ab )2 (0.8mg/kg i.v.) prevented reocclusion in the carotid artery after thrombolysis, no effect was seen on rethrombosis in the jugular vein, reflecting the different thrombotic mechanisms in the arterial and venous circulation. 

A series of events such as the platelet aggregation, hbrinogenesis, hbrin adhesion, hbrin aggregation, and vascular inner wall injury are implicated in the thrombosis. Thus the thrombosis, antithrombosis, and thrombolysis may relate to antiplatelet aggregation [96], chemical- and electrical-induced blood vessel injury [97, 98], thread-induced fibrin or platelet adhesion [99], euglobulin clot lysis time [100,101], fibrinolytic area [102], and reduction of thrombus mass [103,104]. 

Figure 6.3 Effect of two structurally distinct thromboxane A2/prostaglandin endoperoxide receptor antagonists, L636,499 and SQ29,548, on the time to coronary occlusion in the canine model of coronary thrombosis following electrically-induced endothelial injury...

In this preparation, coronary thrombosis is induced by delivery of low amperage electrical current to the intimal surface of the artery according to the method described by Romson et al. (1980a). In contrast to the stenosis protocols, an occluding thrombosis is formed gradually without embolism after some hours (protocol 5). As a consequence of this time course, the thrombi formed are of the mixed type and contain more fibrin than the platelet thrombi with critical stenosis. 

Fig. 5. Model of coronary artery thrombosis in the dog. Electrical injury to the intimal surface of the artery leads to occlusive thrombus formation. The thrombus is formed in the presence of a flow-limiting stenosis induced by a Goldblatt clamp. Upon spontaneous occlusion, heparin is administered, and the clot is aged for 1 h before initiating the t-PA infusion.

Cocaine abuse is a risk factor for myocardial ischemia, infarction, and dysrhythmias, as well as pulmonary edema, ruptured aortic aneurysm, infectious endocarditis, vascular thrombosis, myocarditis, and dilated cardiomyopathy (32). Acutely, cocaine suppresses myocardial contractility, reduces coronary caliber and coronary blood flow, induces electrical abnormalities in the heart, and increases heart rate and blood pressure. These effects can lead to myocardial ischemia (33,34). However, intranasal cocaine in doses used medicinally or recreationally does not have a deleterious effect on intracardiac pressures or left ventricular performance (35). 

S.2.6.3 Electrical Stimulation-Induced Arterial Thrombosis Assay... 

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