A novel hydrodynamic approach to the treatment of coronary artery disease

Abstract

During severe coronary stenosis, capillary resistance increases. Drag-reducing polymers (DRPs) are blood-soluble macromolecules that reduce vascular resistance, possibly by altering blood hydrodynamics and rheology. Thus, we hypothesized that DRPs would enhance myocardial perfusion distal to a severe coronary stenosis. A flow-limiting left anterior descending (LAD) coronary artery stenosis was created in 12 open chest dogs. Coronary driving pressure, flow, trans-stenotic gradient, and radiolabelled microsphere myocardial perfusion were measured. Myocardial contrast echocardiography was performed and videointensity vs. pulsing interval data in the LAD and left circumflex beds were used to derive red cell velocity and capillary volume. Relative to baseline, the stenosis decreased LAD bed capillary volume (P = 0.019) and red blood cell velocity (P = 0.010). Intravenous DRP (polyethylene oxide, 2.5 ppm) decreased LAD microvascular resistance (P = 0.003) and increased microsphere flow (P = 0.009), capillary volume (P = 0.0006), and red cell velocity (P = 0.007) despite the presence of a severe stenosis. DRP did not alter blood viscosity. DRPs improve perfusion to myocardium subserved by a flow-limiting coronary stenosis by decreasing microvascular resistance through an increase in capillary volume. Primary modulation of blood hydrodynamics and rheology to reduce microvascular resistance offers a novel approach to the treatment of ischaemic coronary syndromes.