Protection against atherogenesis with the polymer drag-reducing agent Separan AP-30.

Abstract

The inhibitory effect of Separan AP-30, an anionic polyacrylamide, on atherosclerotic plaque formation in aortas of rabbits on a high (2%) cholesterol diet was tested over a period extending from 37 to 170 days. Atherogenesis was quantified morphometrically by application of a computerassisted image analysis of histologic cross sections of the aorta. The area of vessel wall-atheroma interface, fraction of lumen occluded, and other indexes of atherogenesis were measured in each of 26 segments of aorta excised from the animals, half of which were administered injections (intravenous) of Separan three times a week. Regression analysis of the morphometric data indicates that the polyelectrolyte exerts a powerful antiatherogenic effect in all regions of the aorta, inhibiting the formation of plaque mass to less than half in the aortic arch and about one-fifth in the descending aorta as compared with the aortic plaque masses in untreated rabbits. Results are compatible with the suggestion that a novel hemodynamic principle in vivo, polymer drag reduction, might be effectively applied against atherosclerosis. Circulation 75, No. 3, 627-635, 1987. THE ADDITION of certain linear macropolymers to flow can under certain conditions greatly reduce frictional resistance by polymer drag reduction, an effect also known among hydrodynamicists as the "Toms phenomenon." Flow can thus be increased by threefold or more without alteration of the driving pressure.'-3The effect occurs only in the presence of disturbed or turbulent flow, and it is associated with a laminarization of the flow. This phenomen has also been observed in pipe blood flow with at least four different drag-reducing polymers, 7 including the anionic polyacrylamide Separan AP-30.Application of the polymer drag-reduction principle to blood flow in vivo was first attempted independently From the

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

“…13 Previous studies have demonstrated that intravenous injection of even nanomolar concentration of DRPs increased hemodynamic shear stress 14,15 and decreased peripheral vascular resistance. 16 In this study, we hypothesized that intravenous infusion of DRPs may improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats (SHR) through increasing blood shear stress.…”

Drag reduction by polyethylene glycol in the tail arterial bed of normotensive and hypertensive rats

“…These polymers have been investigated and used for various industrial and engineering applications including crude oil transport through pipelines, firefighting, and reducing drag on ships and submarines (16). When applied to animal models of atherosclerotic plaque these polymers showed beneficial hemodynamic effects including delay/prevention of the development of atherosclerosis in animals kept on an atherogenic diet (8). The literature has reported that DRP are described as long-chain polymers with a molecular weight above 1,000,000 Da (10).…”

“…Classically, the polymer-induced drag-reducing effect occurs in turbulent flows, even though some studies have also described this effect on pulsatile flows in straight and spiral pipes or in Couette flows with Taylor vortices at low Reynolds numbers (6,7). There are results showing that atherosclerotic plaque formation in aortas from rabbits submitted to a high cholesterol diet was reduced by using the polymer Separan AP-30 (8). In addition, the administration of small amounts of DRP may decrease atherosclerosis by increasing shear stress in areas normally exposed to low shear stress (9).…”

Cell Distribution and Segregation Phenomena During Blood Flow

“…These studies were originally motivated by the knowledge that small amounts of long-chain polymer additives-"drag-reducing polymers" (DRPs) -can dramatically reduce drag in turbulent flows while having negligible effect on laminar flows [94]. Studies with laboratory animals indicate that the addition of DRPs to blood leads to many beneficial effects, including (1) reduced atherosclerotic plaque deposition ( Figure 11.3(a)) [90,95]; (2) increased cardiac output [96] and reduced severity of cardiac stenosis or myocardial infarction [97][98][99][100]; (3) improved survival probability after severe hemorrhage with use of polymer-containing resuscitation fluids [91,93,101] (see Fig. 11.3(b)); (4) reduced immune attack of implanted polymeric tissue scaffolds [92] (see Fig.…”

“…Experiments in microfluidic devices [93,105] have shown that the addition of a small amount of DRPs to suspension of RBCs results in a redistribution of RBCs with a significant reduction in the [90]. (b) Survival vs. time for rats subjected to hemorrhage and not treated (CON), treated by injection of normal saline (NS) or intravenously injected with saline containing a drag-reducing polymer [91].…”