Optimizing outcome measurement with murine ferric chloride-induced thrombosis

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The murine FeCl3 model is a widely used model for studying arterial thrombosis, yet provides limited information from each mouse, often only a single time point for the onset of occlusion (defined as the time to occlusion; TTO). To optimize data from the murine ferric chloride model of thrombosis. FeCl3 injury was induced in the carotid arteries of wild-type and Factor IX (FIX) knockout mice, with infusion of recombinant FIX (rFIX) to normalize FIX deficiency at various times around FeCl3 injury. The TTO was recorded as a percentage of baseline flow as occlusion continued to zero flow, with identification of reflow events. The TTO among the treatment groups of FIX-deficient mice showed no statistical differences, except with physiological saline-treated FIX-deficient mice and those receiving delayed treatment. Incidences of occlusion were 100% for wild-type mice and FIX-deficient mice receiving slow infusions of rFIX at early times around the FeCl3 application. In contrast, only 68% of FIX-deficient mice achieved occlusion with preinfusion of rFIX and none occluded with delayed rFIX infusion. A majority of occluded vessels exhibited reflow events, with significantly lower incidence for slow infusion of rFIX starting 4 min after FeCl3 application in comparison with preinjury bolus, demonstrating characterization of a differential response to timing and infusion rates of treatment. Simple use of the time to occlusion may not maximize data available from the FeCl3 arterial thrombosis model. Inclusion of documenting reflow events can extend the useful data obtained with application of this model.

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