Background:
Substantial controversy exists between in-vivo models (increased perfusion) for explanation of mode of action in primary or secondary prevention of chemotherapy-induced peripheral neuropathy (CIPN) with the postulated underlying effect in humans (reduced perfusion) of compression therapy. CIPN severely restricts quality of life as well as therapy options to first-line therapies in cancer patients. We, thus, sought to resolve the physiological basics and potential vascular components in order to substantiate the development of a potential novel CIPN-treatment of dynamic static compression with commercially available compression products with patented palmar or plantar pads (DSC) as well as for the well-established cryotherapy (CT).

Methods:
In 20 healthy volunteers (50% male; age 24.5 ± 4.3 years) and 12 patients with peripheral arterial disease (PAD, 75% male, age: 68 ± 9, 42% longstanding diabetics, serving as positive controls for endothelial dysfunction) as well as 12 chemotherapy (CTX) patients local tissue oxygenation (haem (h) as in haemoglobin and myoglobin) as well as endothelial function were measured with quantitative time resolved near infra-red spectroscopy (NIRS) in response to DSC and CT for up to 90 minutes under standardised and controlled conditions. Microvascular endothelial function was quantified with post-ischaemic reactive hyperaemia. Friedman test with trend (p<0.1) was required before post hoc analyses, Bonferroni-Holm correction was used for multiple comparisons.

Results:
DSC instantly reduced in healthy controls local temperature and metabolic oxygen demand of the intervened hand (dh: -4.6±2.4%) that remained on a low level only influenced by opening of the capillary bed after 5 to 30 minutes (th: +5.6±7.5%, p<0.01) with constant increase of local tissue oxygenation (StO₂: +11.2±7.0%, p<0.001) for the entire 90 minutes driven by increased oxygen supply (O₂h: + 11.7±7.3%, p<0.001) and microvascular perfusion (th: +7.6±8.7%, p<0.005) for the entire compression period. In PAD and in CTX after therapy, magnitude of the increase in tissue oxygenation was significantly lower than in controls (p<0.05 each), whereas reduction of metabolic oxygen demand during DSC was comparable, as evidence of the partial vascular component of the effect of compression therapy. Expectedly, CT induced more pronounced reduction of local temperature and metabolism compared to DSC (p<0.05 each). In contrast to DSC, CT significantly oppressed oxygenation and microvascular perfusion (p<0.05 each). Endothelium-dependent response measured by StO₂ and O₂h was significantly lower in CTX as well as PAD (positive controls) than in controls (p<0.05, each) and reoxygenation rate was more pronounced in controls (p<0.05). Using DSC, endothelium-dependent response was significantly altered in both groups (control: -35% from 163±83 sec, p<0.05 and PAD: -14% from 148±83 sec, p<0.05; p<0.05 for group comparison).

Conclusion:
The results shown here confirm previous experimental studies of CIPN-prevention through vascular reactions enabling optimised perfusion and relative balance of oxygen delivery and diffusion, differing significantly from effects of CT. Furthermore, we here for the first time to our knowledge prove the endothelium-dependent mechanism of damage resulting in CIPN. These results will be validated in upcoming clinical trials to prove this mechanisms of action and deduct specific recommendations to optimise DSC in prevention of CIPN.