Mechanism of Action

The mechanism underlying the effects of EECP is under evaluation but several theories have been postulated.(1-7) The haemodynamic effects of EECP have been theorised to simulate the clinical use of the intra-aortic balloon pump, enhancing cardiac output, stroke volume, and retrograde aortic diastolic flow. EECP produces haemodynamic changes that reduce myocardial oxygen demand in addition to potential for increased transmyocardial pressure to open collaterals. With exposure to the augmented blood flow and endothelial shear stress, there is elaboration of nitric oxide, prostacycline, and vascular endothelial growth factor from the arterial bed that improve endothelial function and vascular remodelling.(2)

Lawson et al reported that EECP seemed to exert a training effect, decreasing peripheral vascular resistance and the heart rate response to exercise.(3) Patients with coronary disease may improve their exercise tolerance after EECP because of both improved myocardial perfusion and a decrease in cardiac workload.

Garlichs et al found reduced serum endothelin-1 concentrations (potent vasoconstrictor) by pneumatic external counterpulsation, which may explain the improved coronary perfusion and vasodilatation after EECP.(4)

Masuda et al showed that EECP induced an increase in both resting and postexercise perfusion (coronary flow reserve representing improved collateral flow) by using 13N-ammonia positron emission tomography.(6) In addition, the study showed that EECP induced a decrease in concentrations of brain natriuretic peptide and an increase in the concentrations of nitric oxide, suggesting an improvement in endothelial function by a neurohormonal mechanism. In another study Masuda et al examined the effect of EECP on the angiogenic factors and reported a 66% increase in human growth factor and β fibroblast growth factor and a 33% increase in vascular endothelial growth factor and monocyte chemoattractant protein 1 (a proinflammatory cytokine).(7)

Urano et al studied patients with significant coronary stenoses before and after completing 35 sessions of EECP. Exercise thallium, gated pool cardiac scintigraphy, left heart catheterisation, and serum assays of atrial natriuretic peptide and brain natriuretic peptide were done. All exercise parameters improved (including exercise duration and time to 1 mm ST depression). Exercise induced perfusion defects, left ventricular end-diastolic pressure and serum brain natriuretic peptide concentrations (which correlated with the left ventricular end-diastolic pressure) were all reduced.(8)

Michaels et al shed new light on the mechanism of action of EECP when they measured left ventricular and intracoronary haemodynamics directly among patients undergoing EECP.(9) Aortic pressure, intracoronary pressure, and intracoronary Doppler flow velocity were measured at baseline and during EECP. EECP resulted in a 93% increase in diastolic and 16% increase in mean intracoronary pressure; there was a 15% decrease in systolic pressure. Coronary blood flow, measured by Doppler and the TIMI (thrombolysis in myocardial infarction) frame count (a quantitative angiographic measure of coronary blood flow), increased by 28%. The study was limited by the assessment of coronary pressures in unobstructed coronaries. Also, the attenuation of coronary flow as a function of autoregulation was not assessed, as the measurements were obtained during EECP.

In summary, it may be postulated that EECP acts by a concert of different contributing mechanisms, both cardiac and peripheral. Acute haemodynamic improvement in terms of diastolic augmentation, improved coronary perfusion and systolic unloading are supplemented by neurohormonal factors. Diastolic augmentation causes increased shear stress, stimulating endothelial growth factors promoting angiogenesis. This may help explain the long term sustained benefits of EECP even after discontinuation of treatment. EECP causes an increase in endothelial production of nitric oxide, prostacycline, and vascular endothelial growth factor and a decrease in brain natriuretic peptide.

References:

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