Enhanced external counterpulsation (EECP) is a non-invasive modality for the treatment of symptomatic coronary disease (CAD) in patients who are not amenable to standard revascularization procedures. EECP is efficacious in decreasing angina episodes, nitrate usage, and hospitalizations, and increasing exercise tolerance and quality of life scores. However, the mechanism(s) underlying for the salutory benefits of EECP remain largely unknown. The popular concept is that EECP may promote collateral development and improve myocardial perfusion. This classical 'angiogenesis' understanding of EECP is a theory and has not been proven in humans. Indeed, there is inadequate data to support the central hypothesis that improved myocardial perfusion is the basis for clinical improvement after EECP. We propose an alternate hypothesis to explain the chronic clinical benefits of EECP. We hypothesize that extra-cardiac factors, such as peripheral arterial stiffness, endothelial dysfunction, and elevated myocardial oxygen demand are the therapeutic target for EECP. To date, the extra cardiac effects of EECP have received little attention and peripheral vascular adaptations to EECP have not been investigated. Specifically, we propose that EECP, by promoting lower extremity arterial """"""""runoff"""""""" and intermittent reactive hyperemia in the legs with each inflation/deflation cycle of the compressive cuffs, improves peripheral vascular function. We further hypothesize that EECP-induced changes in peripheral vascular biology will reduce ventricular work and myocardial oxygen demand in patients with CAD. To test our hypothesis we will randomly assign symptomatic patients with CAD to 35 1-hour sessions of EECP (n=30) or 35 1-hour sessions of sham-EECP (n=30). We will execute the following Specific Aims to determine whether: 1) EECP, as compared to standard care, improves arterial function in symptomatic patients with CAD; 2) EECP, as compared to standard care, improves endothelial function; 3) changes in vascular biology are accompanied by commensurate changes in myocardial oxygen demand; 4) changes in vascular biology are accompanied by commensurate changes in maximal oxygen consumption, ischemic threshold, and anginal classification; 5) changes in vascular biology are accompanied by commensurate changes in vasoactive agents; 6) changes in vascular biology are accompanied by commensurate changes in free radical production and total antioxidant defenses. Only through identification of specific mechanisms behind the efficacy of EECP, will this treatment oDtion receive acceptance by the clinical community in the treatment of svmptomatic CAD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL077571-01
Application #
6814898
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Reid, Diane M
Project Start
2004-08-15
Project End
2007-07-31
Budget Start
2004-08-15
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$363,750
Indirect Cost
Name
University of Florida
Department
Other Health Professions
Type
Other Domestic Higher Education
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
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Beck, Darren T; Martin, Jeffrey S; Casey, Darren P et al. (2014) Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunction. Clin Exp Pharmacol Physiol 41:628-36
Braith, Randy W; Casey, Darren P; Beck, Darren T (2012) Enhanced external counterpulsation for ischemic heart disease: a look behind the curtain. Exerc Sport Sci Rev 40:145-52
Casey, Darren P; Beck, Darren T; Nichols, Wilmer W et al. (2011) Effects of enhanced external counterpulsation on arterial stiffness and myocardial oxygen demand in patients with chronic angina pectoris. Am J Cardiol 107:1466-72
Casey, Darren P; Nichols, Wilmer W; Conti, C Richard et al. (2010) Relationship between endogenous concentrations of vasoactive substances and measures of peripheral vasodilator function in patients with coronary artery disease. Clin Exp Pharmacol Physiol 37:24-8
Braith, Randy W; Conti, C Richard; Nichols, Wilmer W et al. (2010) Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study. Circulation 122:1612-20
Casey, Darren P; Conti, C Richard; Nichols, Wilmer W et al. (2008) Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease. Am J Cardiol 101:300-2