Blood soluble drag‐reducing polymers prevent lethality from hemorrhagic shock in acute animal experiments

Article type: Research Article

Authors: Kameneva, Marina V.^{; ;} | Wu, Zhongjun J. | Uraysh, Arkady^; | Repko, Brandon^; | Litwak, Kenneth N.^{; ;} | Billiar, Timothy R. | Fink, Mitchell P. | Simmons, Richard L. | Griffith, Bartley P.^; | Borovetz, Harvey S.^;

Affiliations: McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15203, USA | Department of Surgery, Medical School, University of Pittsburgh, Pittsburgh, PA 15203, USA | Department of Critical Care Medicine, Medical School, University of Pittsburgh, Pittsburgh, PA 15203, USA | Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15203, USA

Note: [] Corresponding author: Marina V. Kameneva, PhD, McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh, 3025 East Carson St., Pittsburgh, PA 15203, USA. Tel.: +1 412 383 9458; FAX: +1 412 383 9460; E‐mail: [email protected].

Note: [] Current affiliation: Otolaryngology Department, Medical School, University of Pittsburgh, Pittsburgh, PA, USA.

Note: [] Current affiliation: Jefferson Medical School, Philadelphia, PA, USA.

Note: [] Current affiliation: Department of Surgery, School of Medicine, University of Louisville, Louisville, KY, USA.

Note: [] Current affiliation: Division of Cardiac Surgery, University of Maryland, Baltimore, MD, USA.

Abstract: Over the past several decades, blood‐soluble drag reducing polymers (DRPs) have been shown to significantly enhance hemodynamics in various animal models when added to blood at nanomolar concentrations. In the present study, the effects of the DRPs on blood circulation were tested in anesthetized rats exposed to acute hemorrhagic shock. The animals were acutely resuscitated either with a 2.5% dextran solution (Control) or using the same solution containing 0.0005% or 5 parts per million (ppm) concentration of one of two blood soluble DRPs: high molecular weight (MW=3500 kDa) polyethylene glycol (PEG‐3500) or a DRP extracted from Aloe vera (AVP). An additional group of animals was resuscitated with 0.0075% (75 ppm) polyethylene glycol of molecular weight of 200 kDa (PEG‐200), which possesses no drag‐reducing ability. All of the animals were observed for two hours following the initiation of fluid resuscitation or until they expired. We found that infusion of the DRP solutions significantly improved tissue perfusion, tissue oxygenation, and two‐hour survival rate, the latter from 19% (Control) and 14% (PEG‐200) to 100% (AVP) and 100% (PEG‐3500). Furthermore, the Control and PEG‐200 animals that survived required three times more fluid to maintain their blood pressure than the AVP and PEG‐3500 animals. Several hypotheses regarding the mechanisms underlying these observed beneficial hemodynamic effects of DRPs are discussed. Our findings suggest that the drag‐reducing polymers warrant further investigation as a potential clinical treatment for hemorrhagic shock and possibly other microcirculatory disorders.

Keywords: Drag‐reducing polymers, hemorrhage, rats, survival, microcirculation, microchannel flow, viscosity

Journal: Biorheology, vol. 41, no. 1, pp. 53-64, 2004