Background: Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation.
Methods and results: Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F(1α), endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-α, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F(1α) (+71% versus +1%), whereas it decreased endothelin-1 (-25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (-28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-α (-16% versus +12%), monocyte chemoattractant protein-1 (-13% versus +0.2%), soluble vascular cell adhesion molecule-1 (-6% versus +1%), high-sensitivity C-reactive protein (-32% versus +5%), and the lipid peroxidation marker 8-isoprostane (-21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (-62% versus 0%; P<0.001) in treatment versus sham groups, respectively.
Conclusions: Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.