Angiogenic effects of long-term enhanced external counterpulsation in a dog model of myocardial infarction

Abstract

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment of coronary artery disease. Its mechanism of action remains unknown. An acute coronary occlusion dog model was created to explore the angiogenic effect of EECP. After coronary occlusion, 12 dogs were randomly assigned to either EECP ( n = 6) or control ( n = 6). Immunohistochemical studies of α-actin and von Willebrand factor (vWF) were used to detect newly developed microvessels. Systemic and local vascular endothelial growth factor (VEGF) were identified by ELISA and reverse transcriptase PCR analysis. There was a significant increase in the density of microvessels per squared millimeter in the infarcted regions of the EECP group compared with the control group (vWF, 15.2 ± 6.3 vs. 4.9 ± 2.1, P < 0.05; α-actin, 11.8 ± 5.3 vs. 3.4 ± 1.2, P < 0.05). The positive-stained area per squared micrometer also increased significantly (α-actin, 6.6 × 103 ± 2.9 × 103 μm2 vs. 0.6 × 103 ± 0.5 × 103 μm2, P < 0.05; vWF, 5.7 × 103 ± 1.9 × 103 μm2 vs. 1.7 × 103 ± 1.4 × 103 μm2, P < 0.05). Immunohistochemical staining and reverse transcriptase PCR analysis documented a significant increase in VEGF expression. These factors associated with angiogenesis corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography. Angiogenesis may be a mechanism of action for the improved myocardial perfusion demonstrated after EECP therapy.

The Role of Enhanced External Counter Pulsation Therapy in Clinical Practice

“…46 Vascular endothelial growth factors (VEGF) and platelet-derived growth factors that are crucial in angiogenesis are upregulated by vascular shear stress. 47,48 A course of EECP has shown to increase plasma levels of VEGF, basic fibroblast growth factor, and hepatocyte growth factor in a study of 11 patients with stable angina. 49 VEGF is known to induce nitric oxide synthase expression and activity.…”

“…Endothelial nitric oxide stimulates the effect of VEGF on endothelial cells and their organization in networklike structures. 50 In a study of 6-week EECP on 12 beagle dogs, Wu et al 48 demonstrated a significant increase in the microvessels density per mm(2) in the infarcted regions (vWF, 15.2 +/-6.3 vs 4.9 +/-2.1, P < 0.05; alpha-actin, 11.8 +/-5.3 versus 3.4 +/-1.2, P< 0.05) of EECP group compared to control group, respectively. There was also a significant increase in VEGF expression, and they demonstrated that an increase in capillary density corresponded to improved myocardial perfusion by 99mTc-sestamibi single-photon emission computed tomography.…”

The Effects of External Counter Pulsation Therapy on Circulating Endothelial Progenitor Cells in Patients with Angina Pectoris

“…ECPT has been demonstrated to increase plasma nitric oxide and decrease plasma endothelin-1 levels, providing some insight into how ECPT may improve endothelial function [26]. ECPT can stimulate angiogenesis and collateral formation as demonstrated in a dog model of ischemia [10]. The present study proposes a new mechanism of EPC stimulation.…”

“…However, its specific mechanism of action is unclear [1]. Possible mechanisms are diastolic augmentation and increased coronary blood flow, decreased vascular resistance and afterload reduction [2], improved endothelial function [8, 9], and new vessel formation [10]. …”

Enhanced External Counterpulsation Improves Exercise Duration and Peak Oxygen Consumption in Older Patients With Heart Failure: A Subgroup Analysis of the PEECH Trial

“…Prior research, including recent investigations, has illustrated both cardiac and peripheral mechanisms through which patients with obstructive coronary artery disease may achieve symptomatic and functional improvements with EECP. [6][7][8] Previous investigations have reported on the effects of EECP in patients with obstructive coronary disease and left ventricular dysfunction as well as in elderly patients undergoing EECP for treatment of angina. Soran and colleagues 9 showed that in patients with left ventricular dysfunction enrolled in the International EECP Patient Registry, EECP provided significant improvements in angina class, nitroglycerin use, and quality of life.…”