Defense Date

2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Physiology

First Advisor

Roland Pittman

Abstract

Top-loading This study compared the effects on oxygen (O2) transport of four fluids: 5.9% human serum albumin (HSA) a non-O2 carrying iso-oncotic solution (volume control);HBOC-201 (Hemopure, Biopure Corp., Cambridge, MA); MP50, HBOC-201 with a P50 of 18 mmHg; and lastly LP50, an HBOC-201 with P50 of 17 mmHg and higher viscosity (4 cP). It has been proposed that HBOC with a higher O2 affinity and a viscosity closer to that of whole blood will cause less vasoconstriction and thus a lower MAP than Hemopure (P50 = 40 mmHg and 2.2 cP). Intravital microscopic measurements were made on the spinotrapezius muscle of anesthetized, male Sprague-Dawley rats. Interstitial PO2 was measured using phosphorescence quenching microscopy at baseline and following four top-loading infusions, in which increasing concentrations of HBOC-201 were infused to reach target plasma concentrations of 1, 10, 100 and 300 μM. Both HBOC-201 and MP50 increased PO2 by about 10%, but PO2 was unchanged with LP50. LP50 was more hypertensive (160±5mmHg) than HBOC-201 (144±5) and MP50 (141±6). Arteriolar diameters were not significantly different among the three HBOCs. The lower P50 HBOCs did not lead to higher PO2 compared with HBOC-201 and the higher viscosity HBOC led to higher MAP. Hemorrhage and Resuscitation This study compared the efficacy of three resuscitation fluids in a model of hemorrhage and resuscitation: HBOC-201, a hemoglobin-based oxygen carrier ([Hb] = 13 ± 1 g/dl; Biopure Corp.), HBOC-201 with 92 μg/ml nitroglycerin (NTG), and 5.9% human serum albumin, a non-oxygen carrying colloid solution. Intravital microscopic measurements were made on the spinotrapezius muscle of anesthetized, male Sprague-Dawley rats. Interstitial fluid (ISF) oxygen tension (PO2) was measured using phosphorescence quenching microscopy at baseline, post-hemorrhage and three post-resuscitation time points. Following 40% blood volume withdrawal, animals were maintained in this condition for 30 minutes before resuscitation was begun. Baseline ISF PO2 (65 ± 2 mmHg) decreased during hemorrhage (3.6 ± 0.4 mmHg) and all resuscitation fluids increased ISF PO2 towards baseline. HBOC-201 with nitroglycerin produced the highest PO2 throughout the experimental time course, and the findings are consistent with the NO scavenging theory because adding NO alleviated known side effects such as increased vascular resistance and hypertension that are associated with HBOC-201 infusions.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

December 2010

Included in

Physiology Commons

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