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1 Pediatric Cardiology, New York Medical College, Valhalla, NY, USA
* To whom correspondence should be addressed. E-mail: michael_goligorsky{at}nymc.edu.
Endothelial cell dysfunction (ECD) has been demonstrated in patients with end-stage renal disease (ESRD) who have cardiovascular disease (CD) or diabetes mellitus (DM). While techniques to examine conduit arteries have been adapted to these patients, evaluation of microvascular function has lagged behind. Therefore, we used laser Doppler flowmetry (LDF) and scanned laser Doppler imaging (LDI) to quantify parameters of the post-occlusion reactive hyperemia and thermal hyperemic responses (local heating to 43°C) in ESRD patients (N=63) and healthy individuals (n=33). Patients with ESRD were partitioned among those with either CD or DM or both (designated CDorDM, N=30), patients with both CD and DM (designated CD+DM, N=12, statistically similar to CDorDM), and patients with neither CD or DM (designated ~CDorDM, N=33). LDF during thermal hyperemia showed a decrease in the thermal peaks and plateau as well as a delay in plateau compared to control, consistent with ECD. LDF during reactive hyperemia showed a decrease in the "pay-back area under the curve also consistent with ECD. ~CDorDM were heterogeneous: almost 50% contained flow abnormalities similar to CDorDM. There was also a reduction in the number of functional arterioles on LDI images. Fourier analysis of LDF oscillations showed that low-frequency oscillations characterizing endothelial function were impaired in CDorDM and in many ~CDorDM. The data demonstrate that ESRD patients with expected ECD (CDorDM) are characterized by distinct abnormalities in LDF parameters. However, similar abnormalities are found in approximately half of ESRD without evidence for CD or DM. Post-occlusive and thermal interrogation of microvasculature with LD-resolved parameters of microcirculation, followed by Fourier analysis of the very slow oscillations, may provide a valuable adjunct to early non-invasive diagnosis of ECD in ESRD, especially important in a subpopulation of ESRD patients with no known CD or DM, which could be at increased risk of impending clinical manifestations of vasculopathy.
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