Non-invasive Measurement of Microvascular Blood Flow During Mild External Compression of the Leg

Overview

SPECIFIC AIMS The limbs of diabetic patients are associated with decreases in capillary density, arterial inflow, and local blood flow of the leg. Decreased perfusion adversely affects wound healing and viability of tissue, especially in patients with peripheral vascular disease and diabetes. The investigators hypothesize that mild external compression can restore the decreases in skin and muscle blood flow and that there would be greater increases in microvascular blood flow induced by leg compression compared to healthy subjects. Blood flow will be measured using Photoplethysmography (PPG) before, during, and after external compression, and muscle oxygenation will be measured with Near Infrared Spectroscopy (NIRS). The specific aims are: * To measure Muscle Blood Flow (MBF), Skin Blood Flow (SBF), and Bone Blood Flow (BBF) microcirculatory alterations in the leg and foot caused by mild external compression in healthy subjects and patients with diabetes. * To measure muscle oxygenation changes in the leg and foot caused by mild external compression in healthy subjects and patients with diabetes. * To optimize pressures of Continuous Compression to induce maximum microcirculatory blood flow in healthy subjects and patients with diabetes. * To optimize compression pressures, duration, and frequency of Intermittent Pneumatic Compression (IPC) to induce maximum microcirculatory blood flow in healthy subjects and patients with diabetes. * To measure microcirculatory response to compression in patients with diabetes * Continue to validate of photoplethysmography as a tool for measuring microcirculation.

BACKGROUND AND SIGNIFICANCE Therapies utilizing external compression of the leg prevent deep venous thrombosis, decrease lower extremity edema, manage chronic venous insufficiency, and increase healing in the treatment of venous stasis ulcers. In diabetic patients' feet, microcirculation is compromised leading to increased chances of ulcer formation. Therefore, therapies utilizing compression of the lower leg could be beneficial to this population as compression therapies have shown to increase limb perfusion. In recent decades, investigators have found that intermittent compression of the calf or foot can produce acute increases in arterial inflow to a limb. Moreover, intermittent pneumatic compression at high pressures (120 mmHg) increases skin perfusion and popliteal artery inflow. Compression stockings produce much lower pressures (around 20-40 mmHg) but still aid in ulcer healing. The commercial systems have used rapid compression lasting for 3 s or less, with foot and calf pressures (80-100 mmHg). Longer compression durations (10 s at 60 mmHg) with moderate inflation rates in supine patients are effective in increasing flow velocity in the femoral artery, which means that systems do not necessarily need high levels of compression and rapid inflation periods that can be uncomfortable. An optimal therapy for individual patients with peripheral vascular disease should increase microvascular flow in the limb for the longest period possible. Relatively little is known about local circulation in the context of treatment of venous disease with compression therapies. It is known that venous disease decreases muscle and skin oxygenation, and that there are acute and chronic physiologic adaptations to compression therapies such as increases in large and small vessel blood flow and capillary growth. Compression pressures ranging from 20-120 mmHg are used, but there is little physiologic evidence to support an optimal pressure for therapy. Little previous research has looked at the duration of hyperemia during external compression, but for the purpose of therapy it is important, since a compression cycle must set to maximize periods of hyperemia. Another unknown is whether intermittent compression increases blood flow to a greater extent compared to continuous compression. The major variables in compression therapies are compression pressure, duration of compression, and the frequency of compression. The investigators are not aware of any studies to date that have examined these variables in the context of skin and muscle microvascular blood flow in the leg. Photoplethysmography (PPG) is a non-invasive optical technique that measures local microvascular blood flow. PPG directs light from a light emitting diode (LED) toward the skin; light is scattered and absorbed by the skin and deeper tissues. Green light LEDs are placed close to the photodetector to measure skin blood flow. Infrared LEDs are placed farther from the photodetector and penetrate up to several centimeters into underlying muscle. Blood flow changes in the tissue cause changes in the intensity of scattered light recorded by the photodetector. This technique has been validated in multiple studies against invasive methods and is considered to be the best non-invasive measurement of local muscle blood flow. For skeletal muscle, PPG provides equivalent results when compared with the invasive laser Doppler technique. However, frequent motion artifacts and local tissue trauma limit laser Doppler's usefulness. In patients with central venous hypertension due to heart failure, it is hypothesized that increases in compression-induced leg muscle microvascular blood flow will occur in proportion to increases in central venous pressure. It is also hypothesized that in patients with diabetes, increases in compression-induced foot microvascular blood flow will occur in proportion to increases in central venous pressure.