Dynamics of PO and VO in resting and contracting rat spinotrapezius muscle.

This study examined changes in interstitial PO, which allowed calculation of VO during periods of rest, muscle contraction and recovery using an rat spinotrapezius muscle preparation. The PO was measured using phosphorescence quenching microscopy and the muscle VO was calculated as the rate of O disappearance during brief periods of muscle compression to stop blood flow with a supra-systolic pressure. The PO and VO measurements were made during "5 s compression and 15 s recovery" (CR) cycles.

Effect of Hypoxic Blood Infusion on Pulmonary Physiology.

The ability to store red blood cells (RBCs) and other components for extended periods of time has expanded the availability and use of transfusion as a life-saving therapy. However, conventional RBC storage has a limited window of effective preservation and is accompanied by the progressive accumulation of a series of biochemical and morphological modifications, collectively referred to as "storage lesions." These lesions have been associated with negative clinical outcomes (i.

August Krogh's theory of muscle microvascular control and oxygen delivery: a paradigm shift based on new data.

August Krogh twice won the prestigious international Steegen Prize, for nitrogen metabolism (1906) and overturning the concept of active transport of gases across the pulmonary epithelium (1910). Despite this, at the beginning of 1920, the consummate experimentalist was relatively unknown worldwide and even among his own University of Copenhagen faculty. But, in early 1919, he had submitted three papers to Dr Langley, then editor of The Journal of Physiology in England.

Oxygen dependence of respiration in rat spinotrapezius muscle contracting at 0.5-8 twitches per second.

The oxygen dependence of respiration was obtained in situ in microscopic regions of rat spinotrapezius muscle for different levels of metabolic activity produced by electrical stimulation at rates from 0.5 to 8 Hz. The rate of O consumption (V̇o) was measured with phosphorescence quenching microscopy (PQM) as the rate of O disappearance in a muscle with rapid flow arrest.

Barometric calibration of a luminescent oxygen probe.

The invention of the phosphorescence quenching method for the measurement of oxygen concentration in blood and tissue revolutionized physiological studies of oxygen transport in living organisms. Since the pioneering publication by Vanderkooi and Wilson in 1987, many researchers have contributed to the measurement of oxygen in the microcirculation, to oxygen imaging in tissues and microvessels, and to the development of new extracellular and intracellular phosphorescent probes. However, there is a problem of congruency in data from different laboratories, because of interlaboratory variability of the calibration coefficients in the Stern-Volmer equation.

Simultaneous sampling of tissue oxygenation and oxygen consumption in skeletal muscle.

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.

Effects of a hemoglobin-based oxygen carrier (HBOC-201) and derivatives with altered oxygen affinity and viscosity on systemic and microcirculatory variables in a top-load rat model.

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 was also explored, where the P50 and viscosity of the parent compound (HBOC-201) and its modifications (MP50 and LP50A) were as follows: 40mmHg and 3.0cP (HBOC-20l); 18mmHg and 4.

Muscle contraction increases interstitial nitric oxide as predicted by a new model of local blood flow regulation.

The prevailing metabolic theory of local blood flow regulation suggests the dilatation of arterioles in response to tissue hypoxia via the emission of multiple metabolic vasodilators by parenchymal cells. We have proposed a mechanism of regulation, built from well-known components, which assumes that arterioles are normally dilated in metabolically active tissues, due to the emission of NO by the endothelium of microvessels. Regulation of local blood flow aims at preventing an excessive supply of oxygen (O2) and glucose to the tissue and thus provides an adequate supply, in contrast to the metabolic regulation theory which requires permanent hypoxia to generate the metabolic vasodilators.

Effects of non-leukocyte-reduced and leukocyte-reduced packed red blood cell transfusions on oxygenation of rat spinotrapezius muscle.

Leukoreduction of blood used for transfusion alleviates febrile transfusion reactions, graft versus host disease and alloimmunization to leukocyte antigen. However, the actual clinical benefit of leukoreduction in terms of microcirculatory tissue O2 delivery after packed red blood cell (pRBC) transfusion has not been investigated. As such, the aim of this study was to determine the effects of non-leukoreduced (NLR) and leukoreduced (LR) fresh pRBC transfusion on interstitial oxygenation in anesthetized male Sprague-Dawley rats.

Effects of top-loading a zero-link bovine hemoglobin, OxyVita, on systemic and microcirculatory variables.

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.

Bang-bang model for regulation of local blood flow.

The classical model of metabolic regulation of blood flow in muscle tissue implies the maintenance of basal tone in arterioles of resting muscle and their dilation in response to exercise and/or tissue hypoxia via the evoked production of vasodilator metabolites by myocytes. A century-long effort to identify specific metabolites responsible for explaining active and reactive hyperemia has not been successful. Furthermore, the metabolic theory is not compatible with new knowledge on the role of physiological radicals (e.

Oxygen transport in the microcirculation and its regulation.

Objective: Cells require energy to carry out their functions and they typically use oxidative phosphorylation to generate the needed ATP. Thus, cells have a continuous need for oxygen, which they receive by diffusion from the blood through the interstitial fluid. The circulatory system pumps oxygen-rich blood through a network of increasingly minute vessels, the microcirculation.

Oxygen dependence of respiration in rat spinotrapezius muscle in situ.

The oxygen dependence of respiration in striated muscle in situ was studied by measuring the rate of decrease of interstitial Po(2) [oxygen disappearance curve (ODC)] following rapid arrest of blood flow by pneumatic tissue compression, which ejected red blood cells from the muscle vessels and made the ODC independent from oxygen bound to hemoglobin. After the contribution of photo-consumption of oxygen by the method was evaluated and accounted for, the corrected ODCs were converted into the Po(2) dependence of oxygen consumption, Vo(2), proportional to the rate of Po(2) decrease. Fitting equations obtained from a model of heterogeneous intracellular Po(2) were applied to recover the parameters describing respiration in muscle fibers, with a predicted sigmoidal shape for the dependence of Vo(2) on Po(2).

The rate of O₂ loss from mesenteric arterioles is not unusually high.

The 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 O(2) consumption in the microcirculation of the mesentery. We collected ODCs from rapidly arrested blood inside rat mesenteric arterioles using scanning phosphorescence quenching microscopy (PQM).

Skeletal muscle arteriolar function following myocardial infarction: Analysis of branch-order effects.

Diminished bioavailability of nitric oxide (NO) may impair skeletal muscle arteriolar function after myocardial infarction (MI). We tested the hypotheses that chronic MI induced would diminish 1) endothelial function in large (resting diameter ~75μm) feed arterioles, and 2) functional dilation in feed arterioles, but not smaller arcade (~25μm) or transverse (~15μm) arterioles, in the spinotrapezius muscle of female Sprague-Dawley rats. Additionally, we hypothesized that blockade of NO production with N(G)-nitro-l-arginine methyl ester (l-NAME; 30mg/kg i.

Phosphorescence quenching microrespirometry of skeletal muscle in situ.

We have developed an optical method for the evaluation of the oxygen consumption (Vo(2)) in microscopic volumes of spinotrapezius muscle. Using phosphorescence quenching microscopy (PQM) for the measurement of interstitial Po(2), together with rapid pneumatic compression of the organ, we recorded the oxygen disappearance curve (ODC) in the muscle of the anesthetized rats. A 0.

Measurement of oxygen in the microcirculation using phosphorescence quenching microscopy.

According to the classical concept of Krogh, O(2) is delivered to the tissues solely by capillaries and intra-capillary resistance to O(2) diffusion is negligible. Over the past three decades longitudinal PO(2) and SO(2) gradients in arterioles have been observed with a transmural PO(2) gradient in small arterioles of only 1-2 mmHg. Application of phosphorescence quenching microscopy to measurements of PO(2) in arterioles of the rat mesentery by Tsai et al.

Early physiologic responses to hemorrhagic hypotension.

The identification of early indicators of hemorrhagic hypotension (HH) severity may support early therapeutic approaches and bring insights into possible mechanistic implications. However, few systematic investigations of physiologic variables during early stages of hemorrhage are available. We hypothesized that, in certain subjects, early physiologic responses to blood loss are associated with the ability to survive hemorrhage levels that are lethal to subjects that do not present the same responses.

Hemorrhagic shock and nitric oxide release from erythrocytic nitric oxide synthase: a quantitative analysis.

A large loss of blood during hemorrhage can result in profound shock, a state of hypotension associated with hemodynamic abnormalities. One of the hypotheses to account for this collapse of homeostasis is that the production of nitric oxide (NO), a gas molecule that dilates blood vessels, is significantly impaired during hemorrhage, resulting in a mismatch between O(2) delivery and the metabolic activity in the tissues. NO can be released from multiple sources in the vasculature.