Microcirculation and Vascular Reactivity During Endotoxemia and Endotoxin Tolerance in Humans

Abstract

The purpose of the study was to investigate microcirculation and vascular reactivity during experimental endotoxemia and endotoxin tolerance in humans by comparing different methods of approach. Endotoxin tolerance was induced in nine healthy volunteers by intravenous injection of 2 ng . kg(-1) . d(-1) LPS for 5 consecutive days. Microcirculation and vascular reactivity were monitored before and after LPS administrations on days 1 and 5 by near-infrared spectroscopy, sidestream dark-field imaging, and forearm blood flow by venous occlusion strain-gauge plethysmography during local intra-arterial infusion of endothelial-dependent vasodilator acetylcholine (0.5, 2, and 8 microg . min(-1) . dL(-1)). LPS administration induced a significant rise in all measured cytokines. During subsequent LPS administrations, the increase in cytokine levels was almost completely abolished, indicating the development of tolerance. Near-infrared spectroscopy showed 79% (interquartile range [IQR], 62%-92%) attenuation of recovery slope after ischemia 2 h after LPS administration on day 1 (P = 0.04), which was absent on day 5 (P = 0.72). Sidestream dark-field imaging showed 33% (IQR, 14%-40%) and 30% (IQR, 10%-33%) diminished flow in medium and large microvessels, respectively, 2 h after LPS administration on day 1 (P = 0.07 and 0.04, respectively), which was absent on day 5 (P = 0.47 for both vessels). Forearm blood flow measurements showed an attenuation of acetylcholine-induced vasodilatory response, with 67% (IQR, 45%-72%) 4 h after the first LPS administration (P = 0.01), but not when tolerance was present on day 5 (P = 0.61). Human endotoxemia results in endothelial dysfunction that can be adequately detected with different methods and was restored with development of LPS tolerance.

Monitoring the microcirculation in the critically ill patient: current methods and future approaches

“…These alterations can be observed very early in the course of sepsis, even within a few hours of hospital admission [57,101]. Similar alterations, of lower magnitude, can be induced by low-dose endotoxin administration in healthy volunteers [102].…”

Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients

“…It is assumed that the higher the StO 2 recovery slope, the greater the reactive hyperaemia capacities. A recent study reported a 79% decrease in StO 2 recovery slope after an endotoxin challenge in healthy [26]. Accordingly, Creteur et al showed that the StO 2 recovery slope was lower (1) in septic patients than in other categories of patients and in volunteers, (2) in septic patients with shock than without, and (3) in nonsurvivors than in survivors [17].…”

Markers of microbial translocation predict hypertension in HIV‐infected individuals

“…dysfunction [24], among other mechanisms by activating the endothelium through a receptor complex consisting of TLR4, CD14 and myeloid differentiation (MD)-2 [25], and by inducing apoptosis of endothelial cells [26]. Endothelial dysfunction and impaired arterial elasticity are present throughout the atherosclerotic process [27], and an association of LPS with carotid atherosclerosis has been described in the general population [28] as well as in HIV-infected individuals [29].…”