GUIDES

Stimulation of the lymphatics and production of Nitric Oxide (NO) hypothesis

■ Underrecognized in the context of PAD and the use of arterial stimulation by IPC are the effects seen within the lymphatic system. Similar to the arterial endothelium, the lymphatics produce Nitric Oxide (NO) during contraction as a result of shear flow25

■ The lymphatic bulb-valve regions appear to contain the largest density of eNOS, producing approximately a 30 - 50% higher NO concentration compared to the tubular regions25

■ Under environments of increased fluid shear across the lymphatic endothelium there is increased production of NO which causes suppression of lymphatic contraction and pumping (Figure 3)26-29

■ However, the role of NO within the lymphatic system during periods of high lymphatic flow can be thought of as a 'brake' that decreases contractility while simultaneously increasing the diastolic relaxation period, thereby allowing adequate lymphatic refilling and stroke volume30,31

■ This paradoxical effect of NO on lymphatic contractility does not account for increased fluid movement unless the importance of diastolic relaxation is appreciated. IPC use in patients with PAD seems to result in improved fluid management and redistribution from the tissue beds

■ It is hypothesized that stimulation of the lymphatics and production of NO via increased shear force results in increased diastolic relaxation and subsequent filling within the lymphatics and therefore allows for a delayed, albeit increased stroke volume of lymph fluid increasing the propensity of immune cell recognition and activation and increased immune surveillance

■ Beyond increased immune surveillance, NO is also known to exert innate broad-spectrum antimicrobial activity through multiple mechanisms described in the literature without any observation of antimicrobial resistance32-36

■ This is an important area of continued study as systemic production of NO via IPC use or supplementation with L-arginine as a precursor to NO production may be of benefit from not just an arterial point of view, but lymphatic as well