Dog Models

The first dog model described for the study ofvasospasm used a transoral/transclival approach to the chiasmatic cistern (78). In this study, only 42% of the animals experienced SAH after injection of 5 ml of arterial blood. Complications, such as intraventricular hemorrhages, meningitis, and subdural hematomas, developed, and the study showed that some of the animals developed symptomatic vasospasm. However, the authors did not perform lumen patency studies.

The next reported dog model used a craniotomy to implant a strain-measuring device around the ICA and a thread to later avulse the ICA and induce SAH (79). With this technique, acute and chronic vasospasm of the ICA were documented, with peak vasospasm (20% decrease in lumen patency) occurring 4 to 6 days after hemorrhage. This model demonstrated that serial intra-arterial injections of serotonin fail to induce chronic vasospasm. A modification of this technique was developed by avulsing the posterior communicating artery (PCoA) and measuring angiographic diameters (80). Vasospasm after avulsion of the PCoA was more severe than vasospasm after avulsion of the ICA and ranged from 25% to 40%. An acute phase developed 20 min after hemorrhage, followed by a delayed phase 24 hr later.

In the model that followed, 5 ml of blood was injected into the cisterna magna (81), which caused a decrease in the contractility of vasospastic arteries 7 days after hemorrhage. This model has been used to study several experimental treatments, including papaverine (82). Standardization of the angiographic technique and use of a Trendelenberg position for 15 min after injection to encase the subarachnoid clot within the intracranial cisterns improved the reproducibility of this method. The modified technique was reported to induce a 37% decrease in basilar artery vasospasm 30 min and 48 hr after hemorrhage (83,84). Experimental treatments tested in this fashion include Cai+ channel blockers (85 I, NO donors (86), an angiotensin-converting enzyme inhibitor (87), and several NSAIDs (88). Further studies of a single injection of blood into the cisterna magna have shown, however, that this technique does not produce sustained severe vasospasm, and that histopathologic and pharmacologic changes are not consistently present (16,89 ).

To address this problem, the use of multiple injections of blood into the cisterna magna in dogs was proposed (16). This technique induced angiographic vasospasm; however, histo-pathologic or ultrastructural changes were not found. A modification of this technique led to the most popular model of SAH in dogs currently used. It consists of a standardized double injection of 4 ml of blood into the cisterna magna on the first and third days of the study. With this method, angiographic vasospasm of the basilar artery was reported in 82% of animals 5 days after the first injection (90,91). Further analyses showed histopathologic changes in the basilar artery that were associated with a decreased response to treatment with intra-arterial papaverine. Several experimental studies have been performed with this model. Advantages include a well-defined course of vasospasm that is comparable to that of humans, accessible percutaneous angiography, and histopathologic and pharmacologic changes. Disadvantages include limited monoclonal antibodies for analysis, elevated cost, and the need for a second injection.

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