Effects of Remote Ischemic Preconditioning on Moderate PVD Patients A Pilot Randomized Control Trial

Peripheral vascular disease (PVD) is a major health problem, affecting approximately 20% of adults over 55 years of age and about 27 million people in North America and Europe . Most PVD is asymptomatic. Intermittent claudication is the typical clinical manifestation, developing in about 5% men aged 60 years and increases with age . For every patient with symptomatic PAD there are another three to four subjects in general population with PVD who do not meet the clinical criteria for intermittent claudication [4] . There are no precise figures for PVD's health economic impact in Ireland. In the United States, the estimated total cost of PVD exceeds $21 billion annually .

Current treatment options for non-lifestyle limiting claudication include watchful waiting, medical management, exercise training, endovascular treatment and surgical reconstruction with uncertainty regarding the optimal approach in many patients. PVD patients usually have multiple co-morbidities. Decisions regarding optimal management seek to balance the risk of intervention in patients with multiple co-morbidities, the likely benefit in terms of symptom relief and quality of life and the overall life-expectancy of these patients . There is a need for safer, non-invasive interventions which are cost-effective and acceptable to patients.

Ischemic preconditioning was first described by Murry et al, almost 30 years ago when he observed that protection was conferred on ischemic myocardium by preceding brief periods of sub lethal ischemia separated by periods of reperfusion . Subsequent experiments demonstrated that brief periods of ischemia-reperfusion in any tissue conferred protection on any other tissue exposed to a significant ischemic insult. For example, brief periods of skeletal muscle ischemia-reperfusion confers protection on the heart. This phenomenon is referred to as remote ischemic preconditioning (RIPC)

Clinical trials in cardiac surgery and percutaneous coronary intervention suggest that RIPC reduces cardiac injury, critical care stay and inotropes use. However, the effects of preconditioning in peripheral vascular disease patients remain largely un evaluated, apart from some small studies on symptomatic relief and the exercise induced preconditioning effect . Remote preconditioning affects blood supply in other limbs. Enko et al demonstrated that intermittent arm ischemia by applying 3 cycles of 200mmHg pressure for 5 minutes, followed by 5 minutes of reperfusion produced dilatation of the contralateral brachial artery in healthy individuals. In a more recent study, Karakyoun et al evaluated RIPC and direct preconditioning in a rat model of critical limb ischemia. Iliac artery ligation was used to create critical limb ischemia in the rats. Both direct preconditioning (intermittent tourniquet application in the ischemic limb) and RIPC (intermittent tourniquet application on the contralateral leg) produced significant increases in perfusion and microvasculature density in the ischemic limb with true new blood vessels formation in both direct the IC and RIPC groups .

The investigators hypothesize that remote preconditioning as an adjunct to exercise therapy or alone could stimulate greater microvessel formation in the legs of claudication patients, improving clinical outcomes in terms of symptoms and delayed complications. It may provide a new non-invasive option for PVD patients.