Small Animal Hemodialysis Model to Investigate the Effects of Dialysis on Microvascular Tissue Perfusion
Patients with end-stage renal failure (ESRF) require hemodialysis (HD) to clear their blood from metabolic waste products. During HD, blood is pumped through a dialyzer, consisting of a microfiber bundle, usually encased in a semi-transparent polyethylene housing. While generally considered mildly invasive, research shows that HD can induce severe side effects, often affecting microvascular blood flow in tissue.
Although the cause for microvascular disruption is not clear, due to blood coagulation in the microfibers, the increased fluid dynamic shear-forces acting on the flowing blood cells in the remaining open fibers can result in the release of bioactive components due to cell activation and cellular damage. Eventually, these constituents can result in a range of undesirable vascular complications following their return into the patient's bloodstream.
We successfully developed a small animal model that allows us to successfully dialyze laboratory rats (approx. 250 grams) while simultaneously performing an intravital microscopic (IVM) observation of the microcirculation. It will enable us to investigate how microvascular tissue perfusion is affected by HD directly. Moreover, since the microdialyzers are designed and produced in-house, the dialyzer's design and functional aspects can be easily modified. As such, we can easily change the dialyzer setup, evaluate different membrane materials, modify the HD procedure, or evaluate the effect of any pharmacological treatment strategy.
We recently adopted this experimental setup into a unique small animal model to performs an HD procedure on a small-sized rat (200-250 gram). We successfully scaled down a normal dialyzer into a functional mini-dialyzer unit and significantly reduced the system's extracorporeal blood volume. The dialyzer is connected to a catheter in the femoral artery and tail vein for the blood supply to the dialyzer and return to the systemic blood flow, respectively. The blood pumped through the extracorporeal circuit through a small blood pump, while two pumps are used to pump the dialysate fluid to and from the dialyzer.