Large vessel ischemic stroke represents the most disabling subtype. While t-PA and endovascular thrombectomy can recanalize the occluded vessel, good clinical outcomes are not uniformly achieved. We propose that supplementing endovascular thrombectomy with superselective intra-arterial (IA) verapamil immediately following recanalization could be safe and effective. Verapamil, a calcium channel blocker, has been shown to be an effective IA adjunct in a pre-clinical mouse focal ischemia model. To demonstrate translational efficacy, mechanism, feasibility, and safety, we conducted a group of translational experiments. We performed in vivo IA dose-response evaluation in our animal stroke model with C57/Bl6 mice. We evaluated neuroprotective mechanism through in vitro primary cortical neuron (PCN) cultures. Finally, we performed a Phase I trial, SAVER-I, to evaluate feasibility and safety of administration in the human condition. IA verapamil has a likely plateau or inverted-U dose-response with a defined toxicity level in mice (LD 50 16-17.5 mg/kg). Verapamil significantly prevented PCN death and deleterious ischemic effects. Finally, the SAVER-I clinical trial showed no evidence that IA verapamil increased the risk of intracranial hemorrhage or other adverse effect/procedural complication in human subjects. We conclude that superselective IA verapamil administration immediately following thrombectomy is safe and feasible, and has direct, dose-response-related benefits in ischemia.
Cookin' Up Health is a culturally targeted and individualized tailored nutrition intervention using a computer-based interactive format. Using a cooking show theme, the program demonstrates step-by-step meal preparation emphasizing healthy selection and portion control. Focus groups were conducted with women in two rural counties in West Virginia to guide the development of the intervention. Women felt more susceptible to heart disease because the changing role of women creates more stress and less time; weight loss was a greater motivator for dietary change than was preventing heart disease; social support is a barrier and facilitator for dietary change; cultural heritage and the way women were raised were major barriers to making health changes as adults; convenience and the cost of eating healthier were major factors when trying to make changes in diet; and women did not feel confident in their ability to maintain dietary changes.
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