Peripheral artery disease (PAD) is the third leading cause of atherosclerotic cardiovascular morbidity and aff ects one in fi ve patients in primary care [1]. The overall number of PAD patients increased by 23.5 % over the last decade and has become a severe global health problem [2]. Nonsurgical and non-interventional treatment options for PAD patients comprise risk-factor modifi cation, pharmacological therapy and exercise. A supervised exercise program is a highly eff ective treatment option for PAD patients. However, intense training intervals elicit claudication and can be hindered by concomitant morbidities. Thus, novel therapies are needed.External counterpulsation is a non-invasive medical device, wherein pneumatic cuff s are wrapped around the lower limb and are triggered by an electrocardiogram. Upon diastole, the cuff s are infl ated, and at the onset of systole, they are defl ated again. During cuff infl ation, diastolic blood fl ow signifi cantly increases. This, in turn, leads to a profound increase in both intra-arterial shear rate and fl uid shear stress (FSS).Usually, external counterpulsation is applied with high pressures up to 250 or 300 mmHg, which is fre- Summary: Background: External counterpulsation therapy enhances blood fl ow and was shown to improve endothelial function and quality of life in coronary artery disease patients. However, high pressures of up to 300 mmHg may lead to malperfusion of the ischaemic limb. To improve the clinical outcome of patients with peripheral artery disease (PAD), we adjusted external counterpulsation and developed a novel non-invasive approach termed individual shear rate therapy (ISRT). Patients and methods: In the present study, 14 patients with a Fontaine stage IIb and femoral-popliteal PAD underwent 30 hours of ISRT over 5 weeks. For ISRT, individual treatment pressures that do not exceed 160 mmHg were assessed by Doppler fl ow parameters during counterpulsation (individual shear rate diagnosis) in order to enhance and maximise peripheral perfusion. The study aimed to enhance peripheral perfusion and evaluate the primary clinical endpoint endothelial function, as well as to perform preliminary analysis of the ankle brachial index (ABI) and walking distance. Results: Doppler fl ow measurements in the lower limb (ankle) validated that maximum blood fl ow velocity during systole and acceleration doubled during ISRT. Study results demonstrated that long-term ISRT signifi cantly increased fl ow-mediated dilation (FMD) in the brachial artery (0.13+/-0.09 mm to 0.38+/-0.05 mm; p < 0.05), while nitromediated dilation (0.36+/-0.10 mm to 0.45+/-0.08 mm) remained and common femoral artery FMD did not reach statistical signifi cance (0.38+/-0.08 mm to 0.67+/-0.19 mm; p<0.05). Initial claudication distance considerably improved for all patients after 30 hours of ISRT (92.6 +/-8.2 metres to 280+/-101.3 metres, p<0.05), just like the absolute claudication distance, which showed a more than 2.5-fold increase (167.8+/-18.1 metres to 446.7+/-133.3 metres; p<0.05). The...

The prevalence of peripheral arterial disease (PAD) is on the rise in an aging population, significantly affecting quality of life, morbidity and mortality. Besides medical treatment and surgical or interventional revascularization, supervised exercise programs are a primary treatment modality for PAD. Training may significantly increase pain-free walking time (+ 180 %) while avoiding the associated complications of (repeated) invasive revascularization. Training effects rely on an improvement of risk factor management, muscle function, economy of movement, hemorheology, vascular growth and collateral vessel growth. Exercise training upregulates pulsatile fluid shear stress on the vascular endothelium, prompting an improvement of endothelial function (eNOS, NO) and an outgrowth of preexistent collaterals (arteriogenesis) to functional conductance arteries outside the ischemic area at risk. However, the necessary intense minimum training intervals compromise patient compliance, and the impaired functional status of many PAD patients limits active exercise training. Strategies are necessary to a) increase training compliance, b) make the benefits of exercise training available to patients unable to exercise actively and c) therapeutically enhance the adaptive growth of biological bypasses (arteriogenesis). A modified form of “passive exercise training” derived from enhanced external counterpulsation (low-pressure ECP) which was originally developed for the therapy of heart failure, may prove to be an option for this group of patients. Therefore, this review article suggests a tailored combination therapy, consisting of a facilitating revascularization procedure to restore arterial inflow, succeeded by supervised exercise training, which has yielded promising therapeutic results in clinical trials. Further studies, using appropriate imaging methods and controls, are under way to (a) establish the efficacy of low-pressure EECP in PAD patients and (b) to directly correlate training-induced improvements of collateral flow to the functional improvements seen with exercise training.

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.
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