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

Abstract

Objectives: External counter pulsation therapy (ECPT) offers symptomatic relief and improves ischemia in patients with refractory angina pectoris. We aimed to determine the effects of ECPT on circulating endothelial progenitor cells (EPCs). Methods: We prospectively studied 25 patients with angina pectoris treated with ECPT (n = 15) or receiving standard care (n = 10). The number of EPCs positive for CD34 and kinase insert domain receptor (KDR) was determined by flow cytometry and the number of colony-forming units (CFUs) was assessed in a 7-day culture, before ECPT and after 9 weeks. Results: ECPT improved anginal score from a median of 3.0 to 2.0 (p < 0.001). Concomitantly, ECPT increased EPC number from a median of 10.2 to 17.8/10⁵ mononuclear cells (p < 0.05), and CFUs from 3.5 to 11.0 (p = 0.01). Flow-mediated dilatation was improved by ECPT from 7.4 to 12.2% (p < 0.001) and correlated with EPC-CFUs (r = 0.461, p = 0.027). The levels of asymmetric dimethylarginine were reduced by ECPT from 0.70 to 0.60 µmol/l (p < 0.01). In contrast, the same parameters did not change in the control group, before and after follow-up. Conclusions: The present pilot study shows, for the first time, that ECPT is associated with increased number and colony-forming capacity of circulating EPCs.

Effect of enhanced external counterpulsation treatment on renal function in cardiac patients

“…It has been proposed that chronic exposure of coronary and peripheral arterial bed to the augmented blood flow and increased shear forces produced by EECP could lead to increased endothelial cell production of nitric oxide (NO), prostacyclin [25] as well as lead to the development of collateral vessels through the release of angiogenic growth factors [26,27] and increased circulating endothelial progenitor cells [28]. In experimental dogs, EECP increased the density of microvessels in the infarcted regions significantly compared with the control group [29].…”

Letter by Gloekler et al Regarding Article, “Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic Angina: A Randomized Sham-Controlled Study”

“…4 Furthermore, in our study, and in other previous studies, as well, an improvement of brachial artery flow-mediated vasodilation in patients with coronary artery disease after ECP therapy has already been demonstrated. 2,5 Because vasodilation is the first step in the genesis of collateral growth, it is reasonable to note that we observed a direct association between improvement of flow-mediated vasodilation and coronary collateral flow. 5 It is interesting that Barsheshet et al 5 found an inhibitory effect of ECP on plasma levels of asymmetrical dimethylarginine (an endogenous inhibitor of nitric oxide synthases) that is associated with impaired endothelial function and may also prevent collateral growth.…”

“…2,5 Because vasodilation is the first step in the genesis of collateral growth, it is reasonable to note that we observed a direct association between improvement of flow-mediated vasodilation and coronary collateral flow. 5 It is interesting that Barsheshet et al 5 found an inhibitory effect of ECP on plasma levels of asymmetrical dimethylarginine (an endogenous inhibitor of nitric oxide synthases) that is associated with impaired endothelial function and may also prevent collateral growth. Whether flow-mediated vasodilation of the brachial or femoral artery can serve as an adequate marker for fluid shear-stress-induced growth of coronary collaterals remains uncertain, but it at least elucidates in part the beneficial mechanism of ECP: By addition of a diastolic shear-stress signal, the function of preformed coronary collaterals is improved by collateral growth, leading to the clinical effects desired.…”

Transient Extremity Ischemia Augments CD34+ Progenitor Cell Availability

“…A variety of factors have been proposed to act singly or in concert as mediators of this process [34]. Furthermore, recent reports have demonstrated that IPC has a role in the process of stem cell mobilization and leads to substantial elevation in the number of peripheral blood stem cells [29,35,36]. These investigators suggest that the increased number of circulating EPCs may offer a possible explanation to the observed protective effect of remote IPC.…”