Altered Neutrophil Function in Ventricular Assist Devices

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DESCRIPTION (provided by applicant): Congestive heart failure (CHF) is a growing epidemic in the Western World, afflicting 6 million people in US, with an additional 550,000 new cases diagnosed each year. The one and five year mortality rates for CHF are 10% and 60%. Heart transplantation is gold standard therapy for advanced heart failure, but that remains limited by number (2,200 donor heart available each year) and cost. Ventricular assist devices (VADs) offer an alternative treatment for advanced heart failure by working in parallel with the failing ventricle. The current generation of rotary VADs uses a turbine rotor to impart blood flow, have one year survival rates approaching 85%; however, the technology is limited by cost, complexity, and complication. A leading long term cause of death with VAD therapy is infection and 30% of VAD recipients experience an infection each year. There is very little research which has examined why VAD patients remain so susceptible to infection. We have observed that the neutrophils of VAD recipients and advanced heart failure patients circulate in the blood in an activated state, which does not occur in healthy individuals. We have also developed novel microfluidic devices to simulate the extreme shear forces which blood cells experience when they pass through the VAD. Neutrophils from healthy individuals undergoing millisecond exposure to these forces, became activated, suggesting the high shear in VAD may cause neutrophil activation. However, it is not clear why neutrophil activation would contribute to an infectious susceptibility. To investigate these issues we propose 1) Measure changes in neutrophil activation following high shear exposure, 2) Quantify the adhesive capacity of healthy volunteer neutrophils after high shear exposure in comparison to those from Advanced Heart Failure and VAD patients, 3) Examine changes in neutrophil phagocytic function after high shear exposure and in Advanced Heart Failure and VAD patients.