New Insights into the Microvascular Mechanisms of Drag Reducing Polymers: Effect on the Cell-Free Layer

Abstract

Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion. We studied the effect of various concentrations of DRP on RBC distribution in more relevant round microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo. In round microchannels hematocrit was measured in parent and daughter branch at baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the plasma skimming effect in the daughter branch was eliminated, as parent and daughter branch hematocrit were equivalent, compared to a significantly lowered hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6 ± 1.7 µm. In the control group (saline, N=6) there was a significant increase in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5) reduced CFL significantly compared to corresponding baseline and the control group. After DRP administration the CFL reduced to about 85% of baseline at 5, 15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro findings demonstrate that DRPs induce a reduction in CFL width and plasma skimming in the microvasculature. This may lead to an increase of RBC flux into the capillary bed, and thus explain previous observations of a DRP mediated enhancement of capillary perfusion.

A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

“…In this study, we assessed the effect of DRPs in the process of cardiac and aortic remodeling caused by hypertension and demonstrated that blood shear stress and ET-1 expression may play DRPs are long-chain, blood soluble macromolecules, which have been shown to greatly reduce frictional resistance in both turbulent and laminar flow, known as Toms effect. 13,19 DRPs were initially used in fire fighting, irrigation and petroleum pumping to reduce frictional energy losses in large pipes. Recently, these observations have been extended to the vascular system and some biological effects of DRPs have been reported.…”

Emerging Therapies in Traumatic Brain Injury

“…Drag-reducing polymers (DRPs) at nM levels markedly reduce the resistance of microvascular flow, improving tissue perfusion. 222,223 Drag-reducing polymers, such as long-chain polyethylene glycol (kDa > 10 6 ), improve perfusion and reduce mortality in models of hemorrhagic shock. 224 Drag-reducing polymers thus could maintain brain perfusion despite using a volume-limited resuscitation.…”

Improvement of Impaired Cerebral Microcirculation Using Rheological Modulation by Drag-Reducing Polymers

“…DRP also reduce the near-wall cell-free layer increasing wall shear stress and decreasing plasma skimming at vessel bifurcations (i.e., lowering hematocrit in daughter branches of microvessels), described in vitro [12, 13] and in vivo [14] which could explain protection of the BBB. Recent studies reported that increased wall shear stress restrains expression of proinflammatory cytokines that initiate a signaling cascade leading to activation of BBB damage [15, 16]…”