Abstract
Introduction: Mechanical thrombectomy (MT) for large vessel occlusive (LVO) stroke provides an opportunity to deliver targeted intra-arterial (IA) adjunctive therapies (ATs) to the ischemic brain. We developed a model of selective IA catheterization after transient middle cerebral artery occlusion (tMCAO) in rats to investigate targeted adjunctive therapies. Here we report the brain protective effects of targeted IA flushing with normal saline as an adjunctive therapy to LVO revascularization. Methods: We incorporated a continuous internal carotid artery (ICA) catheter infusion system after tMCAO in Sprague Dawley rats (300-350g). Two groups were studied (N=6/group): Control (tMCAO with IA catheter only) and Flushing (tMCAO with IA catheter and brief intermittent flushing). The Flushing group received 1 min infusions of normal saline at 2cc/min immediately, 1hr, and 2hrs after reperfusion. Laser Speckle Imaging was used to measure microvascular perfusion at baseline, post-occlusion, post-reperfusion, and 24hrs post-reperfusion. Functional measurements and histological analysis were performed at 24hrs post-reperfusion. Results: Incorporating a IA catheter system after tMCAO was safe in rats. Flushing saline into the ICA caused a targeted, significantly increased microvascular perfusion of the ischemic MCA territory (P<0.05). Histological analysis demonstrated a significant (P<0.05) decrease in total and cortical infarct size and cortical and striatal swelling. Functional measurements were also significantly decreased (P<0.05) by intermittent flushing. Conclusion: Continuous intra-arterial catheter access can be safely incorporated into a rat model of transient middle cerebral artery occlusion. Here we demonstrate that intermittent targeted flushing of the ischemic brain can be effective as an adjunctive therapy to LVO revascularization. It is now possible and necessary to investigate targeted IA therapeutics after tMCAO in rats.
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