Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study

Abstract

Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

Keywords: endothelial function; flow-mediated dilation; nitric oxide; passive leg movement; sepsis.

Figures

Fig. 1.

Patient screening, enrollment, and follow-up. FMD, flow-mediated dilation; PLM, passive leg movement; ESRD, end-stage renal disease.

Fig. 2.

Brachial artery flow-mediated vasodilation (FMD) assessed in patients with sepsis or septic shock (n = 17) and controls (n = 11) expressed as (A) % dilation and (B) % dilation normalized for the shear stress stimulus. Data presented as means ± SE. *Significantly different from the controls (P < 0.05).

Fig. 3.

Passive leg movement (PLM)-induced hyperemia in patients with severe sepsis and septic shock (n = 13) and controls (n = 16) expressed as (A) the blood flow response [inset is the quantification of the response as area under the curve (AUC] for the first 40 s of PLM) and (B) the change in the blood flow (inset is the AUC analysis). Data presented as means ± SE. *Significantly different from the controls (P < 0.05).

Fig. 4.

A–D: relationships between the indices of the passive leg movement (PLM) assessment, the brachial artery flow-mediated vasodilation (FMD) test, and severity of disease (APACHE II score) in patients with severe sepsis and septic shock.