Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02087-y

Influence of peripheral transluminal angioplasty on top of exercise training on oxidative stress and inflammation in patients with peripheral arterial disease

F. Koppe-Schmeißer1, M. Schwaderlapp2, J. Schmeißer1, J. Dopheide3, T. Münzel1, A. Daiber4, C. Espinola-Klein2

1Kardiologie 1, Zentrum für Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz; 2Kardiologie 3, Zentrum für Kardiologie, Universitätsmedizin der Johannes-Gutenberg Universität Mainz, Mainz; 3Departement Innere Medizin - Angiologie, Kantonsspital Graubünden, Chur, CH; 4Labor für Molekulare Kardiologie, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz;

Background Inflammation leads to production of reactive oxygen species (ROS) causing endothelial dysfunction and thus aggravation of atherosclerosis. In patients with intermittent claudication, home-based exercise training is effective and reduces the level of oxidative stress by a reduction of ROS production and inflammation markers. To date, little is known about the influence of endovascular therapy such as peripheral transluminal angioplasty (PTA) in addition to exercise training on oxidative stress and inflammation in patients with peripheral artery disease (PAD). Methods For the study, we included 41 patients with intermittent claudication Rutherford 3 with ankle-brachial-index <0.9. 21 patients underwent endovascular revascularisation (ER) by PTA, 20 patients without ER served as controls. The decision whether to perform a PTA or not was based on symptom severity in daily-life and patient`s preference. All of the patients were referred to a home-based exercise training program. Absolute claudication distance (ACD) and initial claudiaction distance (ICD) were measured after standard protocol on a treadmill with 10% slope at a speed of 3.0 km/h as well as ankle-brachial index (ABI) at baseline and follow-up. ROS formation was measured using the luminol analogue L-012. Peripheral blood leucocytes [monocytes, polymorphonuclear neutrophils (PMN) and dendritic cells (DC)] were analysed by flow cytometry. Follow-up was performed after 3 months. Results At follow-up, ABI showed a significant increase in the PTA group (p < 0.001), but not in the control group (p = 0.127). Comparing ABI measurements at follow-up between the PTA and control group, there was a significant difference in favour of the PTA group (p = 0.047). Both groups showed a significant increase of ACD and ICD at follow-up  (PTA group: ACD: p = 0.001; ICD: p < 0.000), control group: ACD: p < 0.041; ICD: p < 0.002). There was no significant difference with regard to ACD or ICD between the two groups at follow-up (ACD: p = 0.421; ICD: p = 0.839). ROS production after NADPH oxidase 2 (NOX2) stimulation with basal 20min showed a significant reduction in both groups at follow-up (PTA group: p = 0.002, control group: p = 0.019). Relative reduction of ROS production after NOX2 stimulation under basal conditions at follow-up was significantly higher in the PTA group than in the control group (p = 0.014). NOX2 stimulation by porphol 12, 13-dibutyrates (PDBU) showed a reduction of ROS production at follow-up in both groups, but missed the point of significance. Conclusion To our knowledge, we report here for the first time a reduced ROS production, paralleled by an improvement of clinical parameters such as ABI, ACD and ICD after a combination of endovascular therapy and exercise training. Endovascular therapy in combination with exercise training leads to a lower leukocyte activation state as revealed by reduction of whole blood NOX2-derived ROS production and thus improving ABI, ACD and ICD.

https://dgk.org/kongress_programme/ht2022/aBS662.html