Long-term individual shear rate therapy counterpulsation enhances plasma nitrite release in patients with PAD

Background: Individual shear rate therapy (ISRT) has been designed as a novel non-invasive treatment option for peripheral artery disease (PAD) patients and has been shown to improve endothelial function and walking distance.The aim of this study was to elucidate the impact of ISRT on the level of nitric oxide in patient blood plasma and the expression of related molecular markers in peripheral blood mononuclear cells (PBMCs). Molecular diagnostic tests were performed for two ISRT trials. Patients and methods: In ISRT-1 26 healthy subjects underwent one session of treadmilt training and one session-of ISRT respectively in a cross-over design. In ISRT-2 14 PAD patients with a stable intermittent claudication underwent a 30 hours long-term treatment. Plasma nitrite release as well as the mRNA expression of NOS2 and key regulators of the katlikrein-kinin system were measured in PBMCs at different time points. Results: Short-term ISRT revealed significantly decreased NOS2 expression in PBMCs of healthy volunteers and PAD patients. Long-term ISRT, in turn, demonstrated a significant plasma nitrite increase in PAD patients. Conclusions: We verified that long-term ISRT stimulates the vascular system and exerts a comparable effect to physical exercise in regards to NO release, which coincide with recent findings regarding an improvement of,endothelial function. However, further studies are necessary to investigate the role for circulating leukocytes.