Intermittent negative pressure to improve peripheral blood flow – long term clinical effects and mechanisms of action

Since the 1930s, intermittent negative pressure (INP) has been tested as a means of treating vascular diseases. Recently, the literature has indicated that INP can be used to reduce pain and facilitate wound healing in patients with peripheral arterial disease (PAD) however the physiological mechanism behind these clinical benefits remains unclear. The aim of this study was to evaluate the physiological effects of INP application, in particular vascular function, in both healthy and diseased physiology. INP was applied to the lower limb of PAD patients using the Flow-Ox device with applies a negative pressure of -40mmHg in intermittent cycles of 10 seconds negative pressure followed by 7 seconds of no pressure. Patients were assessed at baseline, after one INP session and after up to 8 weeks of repeated INP application. Vascular function was evaluated through assessment of blood perfusion and endothelial function using full field laser speckle contrast imaging. Systemic effects of INP on vascular function was tested by measuring arterial stiffness, in particular augmentation index and pulse wave velocity. Blood samples were collected to assess blood inflammatory and oxidative stress markers. Clinical markers including ankle-brachial pressure index and pain score were also evaluated. This study demonstrated that after one session of INP application, cutaneous blood perfusion and endothelial function local to the site of INP application improves in PAD patients. Further, patients reported a significantly lower pain score after up to 8 weeks of INP application compared to baseline. No other significant findings were recorded for any other the other assessments. As microvascular function is severely impaired in PAD, the potential of using INP as a novel treatment modality capable of improving microvascular circulation and function with benefits in reducing pain and wound healing warrants further investigation.

This project has aided in uncovering the physiological mechanisms behind the clinical benefits seen in patients with peripheral arterial disease (PAD) with application of intermittent negative pressure. For Otivio, it is important to understand the physiological mechanisms underlying the clinical benefits which have been well documented previously in order to help determine which patients may benefit the most from treatment. The results from this study suggest that microvascular endothelial function significantly improves in PAD patients after one INP session. This result helps to explain the increases in blood flow observed in patients as well as wound healing and reduced ischaemic pain.

Peripheral arterial occlusive disease (PAOD) is a condition characterized by atherosclerotic occlusive disease of the arterial blood vessels to the lower extremities. As a result, all individuals with PAOD are at an enlarged risk of cardiovascular morbidity and mortality. The clogged arteries restrict blood flow to the leg muscles, leading to excruciating pain, cramping, or aching in the calves, thighs, or buttocks that appears during exercise and is relieved by rest. The options for treatment of PAOD include medical treatment or intervention/revascularization (endovascular or open reconstruction). Besides supervised exercise, which is a major treatment modality for patients with PAOD, there have been very few significant breakthroughs in the treatment of PAOD. Endovascular treatment and surgery of lesions above the level of the groin show good long-term results, while the results of intervention below the level of the groin are significantly lower. Additionally, significant proportions of patients have inoperable vascular disease because of co-morbidities such as cerebrovascular and coronary heart disease which contraindicate surgical intervention. Hence, there is an urgent need for new treatments. Otivio has developed a non-invasive method designed to increase blood flow to an extremity. Recently the company has together with partners documented short term improvement in blood flow in different types of patients. Some of these patients (cases) have used the device for several months and achieved significant improvement in their clinical condition. The aim of the present project is to better understand the physiological changes that are the basis for such clinical benefits.