A novel MCA occlusion model of photothrombotic ischemia with cyclic flow reductions: Development of cerebral hemorrhage induced by heparin

Intracerebral hemorrhage is the major complication associated with antithrombotic and thrombolytic therapy. Despite efforts directed toward achieving hemorrhagic infarction, an ideal animal model of cerebral hemorrhage has not yet to be established. Using the photothrombotic technique in rabbits, we developed a model of cerebral hemorrhage by inducing cyclic flow reductions in the middle cerebral artery (MCA). Furthermore, the hemorrhage increased 4-fold after infusion of heparin at a dose prolonging activated partial thromboplastin time by about three times that of control animals. The photothrombotic occlusion of the MCA is based on a thrombosis induced by endothelial injury through singlet oxygen produced by Rose Bengal injection and green light irradiation (Acta Neuropathol. 72 (1987) 315; Acta Neuropathol. 72 (1987) 326; J. Pharmacol. Toxicol. Methods. 29 (1993) 165). Using a pulse Doppler flowmeter, spontaneous reperfusion of the MCA after the thrombotic occlusion following cyclic flow reductions was observed within 2 h in the majority of animals. This model is unusual with respect to the development of clinical stroke, because of the MCA cyclic flow reductions. Thus it is different from permanent or ischemia/reperfusion MCA occlusion in rodents and may be suitable for studying hemorrhagic risks associated with the use of antithrombotic agents.