Grant: Project Grant

Despite ongoing developments in surgical approaches and pharmacotherapies, cardiovascular disease (CVD) remains a leading cause of mortality in Canada, accounting for approximately 1 in 5 deaths in 2022. Of these, almost half are due to ischemia heart disease, which is broadly characterized by a lack of blood flow and oxygen to the heart muscle. There is increasing evidence that the ischemic process is characterized by an over-reacting immune system, specifically an overabundance of prolonged inflammation. As such, recent pre-clinical and clinical work has investigated the use of anti-inflammatory agents to treat patients with ischemic heart disease. While met with initial success, this type of therapy is hindered by the lack of a targeted approach to ensure local agent delivery. In parallel, focused ultrasound (US) is currently surging as a non-invasive, image-guided therapeutic tool in Canada. Indeed, its most recent success is within neurological applications, where it is used to locally deliver otherwise impermeable agents to the brain. Here, our overall goal is to develop a non-invasive, image-guided cardioprotective technique for ischemia immunotherapy. We intend to achieve this using a two-pronged approach: firstly, we will examine via benchtop experiments using our cutting-edge US-coupled microscopy system the influence of blood flow conditions (e.g. varying degrees of ischemia) on US induced immune-related bioeffects, including the modulation of inflammatory signaling, and the enhancement of vascular permeability. Next, in a pre-clinical model of CVD, we will develop an US image-guided focused US treatment program to enable the local delivery of a strong anti-inflammatory agent (antibody against interleukin 1; IL-1b). In the manner, we hope to establish the feasibility of US-assisted cardiac immunotherapy, which has the potential to impact a very large patient population.