Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats

Abstract

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Update on Hemodialysis-Induced Multiorgan Ischemia

“…This has been well demonstrated in epidemiologic, observational, 46 and experimental studies. 47 This may be associated with discrete episodes of intradialytic hypotension or subclinically with more subtle reductions in BP, 48 aggravated by underlying inadequate vasomotor responses. When considering acute cardiac injury during hemodialysis, an ultrafiltration volume of 1 L is associated with a five-fold higher risk.…”

“…This has been observed in both positron emission tomography (PET) 55 and magnetic resonance imaging (MRI) 48 -based studies in humans and animal-based studies of hemodialysis. 47 Microvascular dysfunction involves the maldistribution of tissue blood flow, causing an underperfusion of tissue areas. Microvascular dysfunction develops rapidly and has been observed in several conditions.…”