Harnessing the latent heat of saline evaporation for safe and effective endovascular therapeutic organ cooling

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PROJECT SUMMARY Ischemic stroke represents the second leading cause of death worldwide, costing approximately $71.6 billion. These costs are disproportionately driven by patients with large vessel occlusions (LVO). Recent advances in urgent thrombectomy have led to improved outcomes, yet more than 50% of patients fail to achieve good functional outcomes even in the most recent trials. Developing neuroprotectants to mitigate neuronal injury during and immediately following the ischemic event is now a primary focus for researchers in this area. Among numerous proposed neuroprotectant strategies, hypothermia remains the most promising. Numerous previous investigators have proposed selective brain cooling in conjunction with thrombectomy procedures since the access catheters to the carotid arteries are already in place and could be utilized immediately after clot removal. These selective cooling approaches use either infusion of cold saline directly into the intracranial blood flow or cold saline to cool flowing blood as it passes along an indwelling catheter wall. Both approaches are limited by the cold saline's inherent warming as it travels to the target location. Further, these techniques cannot be implemented until the thrombectomy procedure has concluded, missing an opportunity to maximize the protective cooling effect of penumbral tissue via collateral flow during the thrombectomy procedure itself. The long-term goal of this research and development proposal is to enable an entirely new approach to selective brain cooling using saline as a refrigerant, which is evaporated at ultra-low pressure within the catheter system. The saline phase change from liquid to vapor acts as a heat sink that is orders of magnitude larger than the simple convection/conduction of saline infusion alone. Further, the vacuum used to enable this phase change also acts as an ideal insulator for a concomitant microcatheter system for infusion of cold saline into the intracranial circulation. Last, the cooling device also serves as a state-of-the-art guide catheter that allows cooling to be implemented at the beginning of the thrombectomy procedure, thus optimizing the cooling intervention, rather than waiting until after clot removal as with competitive devices. The first Aim of this R21 proposal involves design, construction, and bench-testing of a coaxial infusioncatheter capable of efficiently vaporizing saline within an annular space, separated from the vasculature and central working lumen for the thrombectomy procedure. Milestones will include heat transfer and mechanical design metrics. During Aim 2, we will carry out in vivo tests assessing the efficacy and safety of our active coolingcatheter. The research plan will involve fabrication and testing of multi-lumen catheters with clearly defined Milestones to achieve acceptable heat transfer metrics, kink, stiffness, torque, and pressure thresholds to maximize heat transfer while minimizing overall system outer diameter. The research plan will include placementof the device in the carotid and renal arteries in swine, measuring the speed, depth, and duration of parenchymal cooling compared to passively-insulated catheters, and assessment of local and systemic adverse reactions.