Physical-plasma device for catheter-based cardiovascular treatment - Abstract: A physical-plasma catheter for treatment of cardiovascular disease will be optimized, manufactured, and tested and its effects on S. aureus biofilms associated with infective endocarditis will be evaluated. Infective endocarditis (IE) is a bacterial infection of the endocardium of the heart or prosthetic implants that has a high rate of mortality (25 – 30 %) and a high necessity for surgical intervention (50%). Multiple species are potential causative agents of endocarditis including S. aureus, S. epidermidis, enterococci, and streptococci, but the leading pathogen is S. aureus. Physical-plasma, an ionized fluid consisting of electrons, ions, and chemically- reactive neutral and excited species has been demonstrated to have many applications in biomedicine, particularly related to infection control. Physical-plasma has shown efficacy against a wide range of pathogens including bacteria, virus, fungi, and spores. In addition, it has also been demonstrated to disrupt protective biofilms on bacteria. We have previously developed and demonstrated a physical-plasma device that can produce plasma in biological liquids, killing biofilm-protected S. aureus bacteria without producing bubbles that would lead to gas embolism in clinical application. Complementary addition of vancomycin further increased the efficacy. It has also been demonstrated benign on cultured murine endothelial cells and human endothelial cells (HAEC) under the same treatment conditions. However, this previous work has shown that the spatial effect of physical-plasma needs to be increased to be an effective intervention. Our hypothesis is that physical-plasma delivered directly to the site of endocarditis by means of a cardiovascular catheter will reduce mortality and decrease reoccurrence of the infection. Moreover, it is expected that physical-plasma can be used as a complementary therapy with antibiotics by disrupting biofilm protection of bacteria and allowing antibiotic molecules to reach the underlying bacteria. Three specific aims will be pursued to prove this hypothesis: (1) Integrate an micro-electrode physical-plasma array (MEPPA) and extruded catheter body while optimizing design and materials for animal trials and future clinical applications; (2) Evaluate physical-plasma efficacy against biofilms in a dynamic, flowing environment including potential for circulating vegetative bacteria, biofilm fragmentation, and interaction with complementary antibiotics.; (3) Evaluate the physical plasma catheter for safety and efficacy in a New Zealand white rabbit model of infective endocarditis. Overall success of these specific aims will result in the development of a fully-integrated physical-plasma catheter that demonstrates effective destruction of S. aureus biofilms associated with infective endocarditis, including in an appropriate animal model. Next steps will include larger animal studies and clinical trials of this ground-breaking technology.
