Under physiologic conditions, microvascular oxygen delivery appears to be well matched to oxygen consumption in respiring tissues. We present a technique to measure interstitial oxygen tension (PISFO2) and oxygen consumption (VO2) under steady-state conditions, as well as during the transitions from rest to activity and back. Phosphorescence Quenching Microscopy (PQM) was employed with pneumatic compression cycling to achieve 1 to 10 Hz sampling rates of interstitial PO2 and simultaneous recurrent sampling of VO2 (3/min) in the exteriorized rat spinotrapezius muscle. The compression pressure was optimized to 120–130 mmHg without adverse effect on the tissue preparation. A cycle of 5 s compression followed by 15 s recovery yielded a resting VO2 of 0.98 ± 0.03 ml O2/100cm3 min while preserving microvascular oxygen delivery. The measurement system was then used to assess VO2 dependence on PISFO2 at rest and further tested under conditions of isometric muscle contraction to demonstrate a robust ability to monitor the on-kinetics of tissue respiration and the compensatory changes in PISFO2 during contraction and recovery. The temporal and spatial resolution of this approach is well suited to studies seeking to characterize microvascular oxygen supply and demand in thin tissues.

The effects of a polymerized bovine hemoglobin-based oxygen carrier (HBOC) and two derivatives on arteriolar vasoactivity and tissue oxygen tension were explored by administering HBOC in a dose-response fashion to normovolemic rats. The effect of oxygen affinity (P50) and viscosity were also explored, where the P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50 and LP50A) were as follows: 40 mmHg and 3.0 cP (HBOC-20l); 18 mmHg and 4.4 cP (MP50); and 17 mmHg and 12.1 cP (LP50A). Anesthetized male Sprague-Dawley rats (N = 32) were randomized to receive one of the HBOC solutions, and were administered four infusions that increased in concentration for each dose (2, 22, 230 and 780 mg/kg, IV). Data were compared to rats receiving an equivalent volume for each of the four infusions (0.4, 0.4, 3.8, 13.1 ml/kg, IV) of iso-oncotic 5.9% human serum albumin (HSA). Increasing doses of either HBOC solutions or HSA were associated with increasing MAP. Doses 3 and 4 of HBOC-201, MP50 and HSA produced significant increases in MAP, whereas similar increases began at a lower dose (Dose 2) with LP50A. There were no significant changes in arteriolar diameters at any dose for any group. Interstitial partial pressure of oxygen (ISF PO2) remained unchanged for HBOC-201, MP50 and HSA, but LP50A caused a significant decrease in ISF PO2 compared to baseline after Doses 3 and 4. In conclusion, there was no evidence that HBOC-201 would perform better with increased oxygen affinity (40 to 18 mmHg) or viscosity (3.0 to 4.4 cP).

This study was designed to test the effect of top-load infusions of increasing doses of two versions of the novel, high molecular weight hemoglobin-based oxygen carrier, OxyVita and OxyVita C solution ([Hb] = 6 g/dL), on mean arterial pressure (MAP), arteriolar diameter, and tissue oxygenation. Experiments were carried out on 18 anesthetized male Sprague-Dawley rats in which microcirculatory observations were made on the spinotrapezius muscle. Intravenous infusions of four increasing doses of the OxyVita solutions (2, 22, 230, and 780 mg/kg) were made for each group, and a separate group of animals was used for volume control. Tissue oxygenation was measured as interstitial fluid (ISF) PO2 using phosphorescence quenching microscopy. Increasing doses of either OxyVita solution or Lactated Ringer's solution (LRS, volume control) were associated with increasing MAP. For LRS infusions, MAP returned to baseline between each incremental dose injected, whereas there was an incomplete return for either of the OxyVita solutions. ISF PO2 for OxyVita was significantly lower than that for either LRS or OxyVita C, whereas ISF PO2 for OxyVita C was never statistically different from LRS. There were no significant changes in arteriolar diameters for LRS and either of the OxyVita solutions.

Resuscitation with SANGUINATE after PHS improves survival, MAP, and PISFO2 compared to standard of care plasma expanders. Since the pathologies of hemorrhagic shock and the associated systemic ischemia are progressive, preclinical studies of this nature are essential to determine efficacy of new resuscitants across the range of possible times to treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

Golub AS, Song BK, Pittman RN. The rate of O2 loss from mesenteric arterioles is not unusually high. Am J Physiol Heart Circ Physiol 301: H737-H745, 2011. First published June 17, 2011 doi:10.1152/ajpheart.00353.2011The O 2 disappearance curve (ODC) recorded in an arteriole after the rapid arrest of blood flow reflects the complex interaction among the dissociation of O 2 from hemoglobin, O 2 diffusivity, and rate of respiration in the vascular wall and surrounding tissue. In this study, the analysis of experimental ODCs allowed the estimation of parameters of O 2 transport and O2 consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM). The technique was used to prevent the artifact of accumulated O 2 photoconsumption in stationary media. The observed ODC signatures were close to linear, in contrast to the reported exponential decline of intra-arteriolar PO 2. The rate of PO2 decrease was 0.43 mmHg/s in 20-m-diameter arterioles. The duration of the ODC was 290 s, much longer than the 12.8 s reported by other investigators. The arterioles associated with lymphatic microvessels had a higher O 2 disappearance rate of 0.73 mmHg/s. The O 2 flux from arterioles, calculated from the average O 2 disappearance rate, was 0.21 nl O2·cmϪ2 ·s Ϫ1 , two orders of magnitude lower than reported in the literature. The physical upper limit of the O 2 consumption rate by the arteriolar wall, calculated from the condition that all O 2 is consumed by the wall, was 452 nl O 2·cm Ϫ3 ·s Ϫ1 . From consideration of the microvascular tissue volume fraction in the rat mesentery of 6%, the estimated respiration rate of the vessel wall was ϳ30 nl O 2·cm Ϫ3 ·s Ϫ1 . This result was three orders of magnitude lower than the respiration rate in rat mesenteric arterioles reported by other investigators. Our results demonstrate that O 2 loss from mesenteric arterioles is small and that the O2 consumption by the arteriolar wall is not unusually large. microcirculation; arterioles; oxygen consumption; phosphorescence quenching microscopy CAPILLARIES PLAY A CENTRAL ROLE in the diffusive O 2 supply to parenchymal cells, as envisioned by Krogh (18,19). For half a century after Krogh's breakthrough, this concept stood as a pillar of experimental research and mathematical modeling of O 2 transport to tissue. Forty years ago, the experimental findings of a longitudinal gradient of PO 2 in arterioles undermined the absolutism of the central role of capillaries and demonstrated the possibility of substantial O 2 loss from blood before it enters the capillaries (5). Longitudinal gradients of O 2 content and partial pressure in arteriolar blood were reported by independent researchers with different measuring techniques (20,21,25,26,37) and were reviewed in Refs. 17 and 38. The contribution of arterioles to the diffusion of O 2 from blood to tissue was established experimentally and received theoretical substantiation (24). Fur...