Effect of oxygenated polyethylene glycol decorated hemoglobin on microvascular diameter and functional capillary density in the transgenic mouse model of sickle cell anemia

Abstract

Malemide polyethylene glycol-conjugated Hb (MP4OX, Sangart Inc.), a high-affinity low-concentration acellular hemoglobin (P50 = 5 mmHg, 4.3 g/dl) solution, has been shown to optimize microvascular perfusion and target oxygen delivery to anoxic tissue. Microvascular perfusion during an acute hypoxic challenge in a transgenic anemic sickle cell disease mouse model was studied with MP4OX and saline. Arterioles were dilated in both groups. Functional capillary density (FCD) was maintained at a higher level with MP4OX. In conclusion, MP4OX treatment reduced the hypoxia-mediated decline in FCD, an effect in part due to higher arterial pressure resulting in increased microvascular perfusion pressures.

Keywords::

• cell-free hemoglobin
• hypoxia
• microcirculation
• perfusion

Acknowledgments

The authors wish to thank Mr. Froilan Barra and Ms. Cynthia Walser for putting their surgical skills to use in the preparation of the window and catheter implantations.

Research contributions: AGT, performed the experiments, analyzed data, designed the study, and wrote a paper; PC, analyzed data; MAY, analyzed data, designed the study, and contributed to the writing of the paper; RMW, analyzed data and contributed to the writing of the paper; and MI, analyzed data and contributed to the writing of the paper.

Declaration of interest

M.I. and R.M.W. hold patents related to the work that is described in the present study. A.G.T., P.C. and M.A.Y. report no declaration of interest. Research was supported in part from grants NIH P01 HL 110900, NIH R01 HL052684 and USAMRMC Contract W81XWH-11-2-0012. The knockout transgenic mice and MP4OX were provided by Sangart through a collaborative research partnership funding from NIH R24 HL064395.