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European Heart Journal Advance Access published online on August 16, 2006
European Heart Journal, doi:10.1093/eurheartj/ehl165
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European Heart Journal © The European Society of Cardiology 2006; all rights reserved
Received April 6, 2006
Revised June 28, 2006
Accepted July 6, 2006

Preclinical research

A novel hydrodynamic approach to the treatment of coronary artery disease

John J. Pacella 1 *, Marina V. Kameneva 2, Melissa Csikari 1, Erxiong Lu 1, and Flordeliza S. Villanueva 1

1 Department of Medicine, Cardiovascular Institute, University of Pittsburgh School of Medicine, S568 Scaife Hall, 200 Lothrop Street, Pittsburgh, PA 15213, USA
2 McGowan Institute for Regenerative Medicine, Pittsburgh, PA, USA

* To whom correspondence should be addressed.
John J. Pacella, E-mail: villanuevafs{at}upmc.edu


  Abstract

Aims During severe coronary stenosis, capillary resistance increases. Drag-reducing polymers (DRPs) are blood-soluble that macromolecules 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.

Methods and results 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.

Conclusions 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.

Keywords: Myocardial ischaemia; Drag-reducing polymers; Myocardial contrast echocardiography; Coronary microcirculation; Ischaemic heart disease.
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