Affiliations: Cardiovascular Institute, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA | McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, USA | Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA | Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA
Note: [] Address for correspondence: Dr. John J. Pacella, University of Pittsburgh, S570 Scaife Hall, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Tel.: +1 412 647 5840; Fax: +1 412 647 4227; E-mail: pacellajj@upmc.edu.
Abstract: We have shown that drag-reducing polymers (DRP) restore perfusion to a stenotic bed by lowering microvascular resistance. We studied whether resistance-lowering by DRP are due to changes in hydrodynamics or vasodilation. During intravital microscopy of rat cremaster muscle (n=18), DRP infusion increased aortic flow (p<0.002), decreased vascular resistance (p<0.01), increased arteriolar diameter (p=0.023), and increased RBC velocity in the arterioles (p<0.04), venules (p<0.003) and capillaries (p<0.02). To investigate whether DRP lowers resistance without involvement of shear (nitric oxide [NO])-mediated vasodilation, L-NAME was infused in 19 rats, but failed to abolish DRP resistance-lowering. To further investigate whether DRP resistance-lowering depends on vasodilation, adenosine was infused into rabbit femoral arteries (n=19) prior to DRP to achieve marked vasodilation. DRP caused an additional 14% decrease in femoral vascular resistance (p=0.022). DRP enhance microcirculatory perfusion by lowering vascular resistance. This involves not only some degree of shear-induced vasodilation, but also tone-independent resistance lowering mechanisms, suggesting that DRP favorably alter blood flow hydrodynamics. Modulation of blood flow hydrodynamics to enhance perfusion is unique, and may be of therapeutic value for any condition of compromised blood flow.
