Intermittent pneumatic leg compressions acutely upregulate VEGF and MCP-1 expression in skeletal muscle

Abstract

Application of intermittent pneumatic compressions (IPC) is an extensively used therapeutic strategy in vascular medicine, but the mechanisms by which this method works are unclear. We tested the hypothesis that acute application (150 min) of cyclic leg compressions in a rat model signals upregulation of angiogenic factors in skeletal muscle. To explore the impact of different pressures and frequency of compressions, we divided rats into four groups as follows: 120 mmHg (2 s inflation/2 s deflation), 200 mmHg (2 s/2 s), 120 mmHg (4 s/16 s), and control (no intervention). Blood flow and leg oxygenation (study 1) and the mRNA expression of angiogenic mediators in the rat tibialis anterior muscle (study 2) were assessed after a single session of IPC. In all three groups exposed to the intervention, a modest hyperemia (approximately 37% above baseline) between compressions and a slight, nonsignificant increase in leg oxygen consumption (approximately 30%) were observed during IPC. Compared with values in the control group, vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) mRNA increased significantly (P < 0.05) only in rats exposed to the higher frequency of compressions (2 s on/2 s off). Endothelial nitric oxide synthase, matrix metalloproteinase-2, and hypoxia-inducible factor-1alpha mRNA did not change significantly following the intervention. These findings show that IPC application augments the mRNA content of key angiogenic factors in skeletal muscle. Importantly, the magnitude of changes in mRNA expression appeared to be modulated by the frequency of compressions such that a higher frequency (15 cycles/min) evoked more robust changes in VEGF and MCP-1 compared with a lower frequency (3 cycles/min).

Fig. 1.

Schematic illustration of intermittent pneumatic limb compression (IPC) application in the rat leg. A blood pressure cuff was wrapped around the left leg and firmly secured with umbilical tape. To prevent cuff displacement during the intermittent compressions, the leg was secured in place. A, catheter on the carotid artery; B, blood flow meter placed on the femoral artery, C, catheter placed on a branch of the femoral vein; D, cuff for application of compressions. See methods for details.

Fig. 2.

Representative recordings of femoral blood flow (FBF) responses to IPC. Blood flow increased temporarily above baseline values following cuff deflation. A: 120 mmHg (2 s on/2 s off). B: 200 mmHg (2 s on/2 s off). C: 120 mmHg (4 s on/16 s off).

Fig. 3.

Net changes in blood pressure (A), FBF (B), and femoral conductance (C) during an acute bout of IPC application. *P < 0.05, baseline is different from compression.

Fig. 4.

Leg O₂ delivery (A), arterial-venous (a-v) O₂ content difference (B), and oxygen consumption (V̇o₂; C) before and after an acute bout of IPC application.

Fig. 5.

Fold changes in mRNA of vascular endothelial growth factor (VEGF; A) and monocyte chemoattractant protein-1 (MCP-1; B) following 150 min of IPC application. The right leg, harvested before the intervention, served as a baseline expression control. Values are means ± SE; n = 8 for 200 mmHg (2 s on/2 s off), 120 mmHg (4 s on/16 s off), and no intervention groups and n = 7 in 120 mmHg (2 s on/2 s off) group. *P < 0.05, different from no intervention group.