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Nanomolar intravascular concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of ischemic myocardium and limb, but the effects of DRP on the cerebral microcirculation have not yet been studied. We recently demonstrated that DRP enhance microvascular flow in normal rat brain and hypothesized that it would restore impaired microvascular perfusion and improve outcomes after focal ischemia and traumatic brain injury (TBI). We studied the effects of DRP (high molecular weight polyethylene oxide, 4000 kDa, i.v. at 2 μg/mL of blood) on microcirculation of the rat brain: (1) after permanent middle cerebral artery occlusion (pMCAO); and (2) after TBI induced by fluid percussion. Using in vivo two-photon laser scanning microscopy (2PLSM) over the parietal cortex of anesthetized rats we showed that both pMCAO and TBI resulted in progressive decrease in microvascular circulation, leading to tissue hypoxia (NADH increase) and increased blood brain barrier (BBB) degradation. DRP, injected post insult, increased blood volume flow in arterioles and red blood cell (RBC) flow velocity in capillaries mitigating capillary stasis, tissue hypoxia and BBB degradation, which improved neuronal survival (Fluoro-Jade B, 24 h) and neurologic outcome (Rotarod, 1 week). Improved microvascular perfusion by DRP may be effective in the treatment of ischemic stroke and TBI.

Chronic testing of the Nimbus/UOP Axial Flow Pump was performed on 22 calves for periods of implantation ranging from 27 to 226 days (average, 74 days). The following parameters were measured: plasma free hemoglobin, blood and plasma viscosity, erythrocyte deformability and mechanical fragility, oxygen delivery index (ODI), blood cell counts, hematocrit, hemoglobin, blood urea nitrogen, creatinine, bilirubin, total protein, fibrinogen, and plasma osmolality. Most of the above parameters were stable during the full course of support. Compared with baseline, statistically significant differences during the entire period of implantation were only found in: hematocrit (p<0.001), hemoglobin (p<0.005), red blood cell (RBC) count (p<0.001), and whole blood viscosity (p<0.01). Plasma viscosity and ODI were mostly stable during the period of implantation. In some animals, an acute increase in fibrinogen concentration, plasma and blood viscosity, and a decrease in ODI were found to be early signs of the onset of infection. A small (10%) decrease in deformability of RBCs was found during the first 2 weeks after implantation. This alteration in RBC deformability was highly correlated (r = 0.793) with changes in total plasma protein concentration that fell more than 15% (p<0.001) during the same period. Mechanical fragility of RBCs was found to be slightly increased after implantation. Plasma free hemoglobin remained close to baseline level (p>0.2). After the first 2 weeks of the postoperative period, pump performing parameters for all animals were consistent and stable. In general, the Nimbus/UOP Axial Flow Pump demonstrated basic reliability and biocompatibility and did not produce significant alterations in the mechanical properties of blood or animal health status. The pump provided adequate hemodynamics and was well tolerated by the experimental animal for periods as long as 7.5 months. Monitoring rheologic parameters of blood is very helpful for evaluation of health during heart-assist device application.

Hemorheologic investigations were performed on nine sheep during the in vivo evaluation of a new axial flow ventricular assist device, the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, CA). Blood hematocrit, plasma and whole blood viscosity, red blood cell (RBC) deformability and aggregation, plasma fibrinogen, and free hemoglobin (hemolysis) levels were measured. Changes in the main rheologic parameters of sheep blood relative to the pre-implant values were minor and transient. The exception was RBC aggregation, which appeared on the third day of implantation. (Sheep blood does not normally demonstrate RBC aggregation.) Sheep RBCs started to form classic rouleaux typically on the third post-operative day simultaneously with increasing fibrinogen level. To investigate the relative effects of mechanical stress and elevated fibrinogen levels on RBC aggregability, in vitro studies were conducted with blood from control sheep. These studies indicated that neither mechanical trauma nor elevated fibrinogen alone caused RBC aggregation as seen in vivo. However, combined mechanical stress and elevated fibrinogen did cause this unusual effect for sheep blood.

One of the major problems of development and improvement of heart assist devices is the reduction of blood cell damage. The extremely high levels of shear stress, turbulence, prolonged contact between blood and foreign surfaces, and other abnormal hydrodynamic circumstances have been shown to cause hemolysis, activation of platelets, and changes in mechanical properties of red blood cells. Hemolysis, in turn, can drastically increase red blood cell aggregation at low shear conditions. A new pharmacologic approach to reduce blood trauma and improve rheologic properties of blood subjected to mechanical stress was investigated. These experiments showed that the replacement of 20% of the plasma volume with Fluosol (Alpha Therapeutic Corp., Los Angeles, CA), a perfluorochemical that transports oxygen, reduced mechanical fragility of human (P < 0.01) and ovine (P = 0.054) red blood cells by approximately 30%. The same replacement of plasma with Fluosol reduced hemolysis (plasma free Hb) by approximately 40% compared to control (P < 0.05) during in vitro pumping of blood with a centrifugal pump. A 20% replacement of plasma volume with Fluosol remarkably reduced low shear blood viscosity (from 31.9 +/- 6.1 to 18.2 +/- 4.8 cP, for shear rate gamma = 0.277 sec-1) and erythrocyte sedimentation rate (from 16.7 +/- 9.2 to 3.1 +/- 3.1) mm/hr) in human blood. Decrease of these parameters indicates the reduction of red blood cell aggregation. Results of this study demonstrate the potential feasibility of Fluosol to improve mechanical properties of blood in patients with heart assist devices.