Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue

Rumsey, William L.; Vanderkooi, Jane M.; Wilson, David F.

doi:10.1126/science.3420417

Cited by 477 publications

(297 citation statements)

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“…The probe binds to albumin and is therefore localized to the plasma phase of the intravascular compartment. In blood, the only molecule that quenches phosphorescence is O 2 (15); thus the lifetime of the phosphorescence originated by excitation of the phosphor is determined by plasma PO 2 . The value of Pm O 2 obtained in …”

Section: Discussionmentioning

confidence: 99%

Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation

Shah

Allen

Wood

et al. 2003

Journal of Applied Physiology

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. Dissociation between skeletal muscle microvascular PO 2 and hypoxia-induced microvascular inflammation. J Appl Physiol 94: 2323-2329, 2003. First published February 21, 2003 10.1152/japplphysiol.01185. 2002 produces microvascular inflammation in mesenteric, cremasteric, and pial microcirculations. In anesthetized rats, SHx lowers arterial blood pressure (MABP), which may alter microvascular blood flow and microvascular PO 2 (PmO 2 ) and influence SHx-induced leukocyte-endothelial adherence (LEA). These experiments attempted to determine the individual contributions of the decreases in PmO 2 , venular blood flow and shear rate, and MABP to the hypoxia-induced increase in LEA. Cremaster microcirculation of anesthetized rats was visualized by intravital microscopy. PmO 2 was measured by a phosphorescencequenching method. SHx [inspired PO2 of 70 Torr for 10 min, MABP of 65 Ϯ 3 mmHg, arterial PO2 (PaO 2 ) of 33 Ϯ 1 Torr] and cremaster ischemia (MABP of 111 Ϯ 7 mmHg, PaO 2 of 86 Ϯ 3 Torr) produced similar PmO 2 : 7 Ϯ 2 and 6 Ϯ 2 Torr, respectively. However, LEA increased only in SHx (1.9 Ϯ 0.9 vs. 11.2 Ϯ 1.1 leukocytes/100 m, control vs. SHx, P Ͻ 0.05). Phentolamine-induced hypotension (MABP of 55 Ϯ 4 mmHg) in normoxia lowered PmO 2 to 26 Ϯ 6 Torr but did not increase LEA. Cremaster equilibration with 95% N2-5% CO2 during air breathing (PaO 2 of 80 Ϯ 1 Torr) lowered PmO 2 to 6 Ϯ 1 Torr but did not increase LEA. On the other hand, when cremaster PmO 2 was maintained at 60-70 Torr during SHx (PaO 2 of 35 Ϯ 1 Torr), LEA increased from 2.1 Ϯ 1.1 to 11.1 Ϯ 1.5 leukocytes/100 m (P Ͻ 0.05). The results show a dissociation between PmO 2 and LEA and support the idea that SHx results in the release of a mediator responsible for the inflammatory response.leukocyte-endothelial interactions; cremaster muscle; microcirculation; ischemia; local hypoxia; tissue PO2 SYSTEMIC HYPOXIA RESULTS IN a rapid microvascular inflammatory response characterized by increases in microvascular reactive O 2 species (ROS) (19,20,24) and in venular leukocyte-endothelial adhesive interactions (26). Rats studied after exposure to 4 h of hypoxia in the conscious state show emigration of leukocytes to the perivascular space and elevated vascular permeability (25). The inflammatory response to hypoxia has been studied predominantly in the mesenteric microcirculation (19-21, 24-26) but has also been observed in venules of the cerebral and cremaster microcirculations (6), indicating that it is a widespread phenomenon. The microvascular lesion eventually resolves; after 3 wk of acclimatization to hypoxia, there is no evidence of leukocyte adherence or emigration in mesentery (26) or cremaster microcirculations (6), and the animals tolerate further reductions in inspired PO 2 without evidence of microvascular inflammation.Although the early response to hypoxia has common features with ischemia-reperfusion, their patterns are quite different and demonstrate that hypoxia and ischemia-reperfusion-induced microvascular inflammation are two distinct phenomena: ...

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Section: Discussionmentioning

confidence: 99%

Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation

Shah

Allen

Wood

et al. 2003

Journal of Applied Physiology

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“…Measuring phosphorescence intensity and lifetime allows quantification of oxygen concentrations (Rumsey et al 1988;Vanderkooi et al 1990). In the case of imaging of cells, this can be accomplished on a pixel-by-pixel basis by applying phasemodulation methods.…”

Section: Figure 10mentioning

confidence: 99%

Platinum Porphyrins as Phosphorescent Label for Time-resolved Microscopy

Haas

Gijlswijk

Tol

et al. 1997

J Histochem Cytochem.

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SUMMARYWe investigated phosphorescent metalloporphyrins as potential labels for time-resolved microscopy. On the basis of spectroscopic analysis of their physicochemical properties (quantum yield, molar absorption coefficient, decay times) the best candidates were selected. Next, we synthesized antibody and avidin metalloporphyrin conjugates. The optimal F/P ratio with respect to quantum yield, decay time, and retention of biological activity of these immunoreagents was determined. The reagents were then evaluated by in situ hybridization and immunocytochemical procedures for demonstration of haptenlabeled DNA probes, membrane antigens (CD type), and 28S rRNA. All stained samples exhibited bright phosphorescence that could be selectively detected using time-resolved microscopy, especially when glucose/glucose oxidase was added to the embedding medium to deplete oxygen. Applications of time-resolved detection of phosphorescent porphyrins in strongly autofluorescent material (histological sections) are discussed.

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“…Based on these phosphorescent properties, porphyrin derivatives have been used as optical oxygen sensors in the aerodynamics field (3,4). It has also been reported that PdTCPP can be used to measure the oxygen concentration in normal tissues (5), in cancer cells (6), or in blood (7). However, the physiological properties of PdTCPP are still unclear.…”

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confidence: 99%

Porphyrin Accumulation in Mitochondria Is Mediated by 2-Oxoglutarate Carrier

et al. 2006

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Heme (Fe-protoporphyrin IX), an endogenous porphyrin derivative, is an essential molecule in living aerobic organisms and plays a role in a variety of physiological processes such as oxygen transport, respiration, and signal transduction. For the biosynthesis of heme or the mitochondrial heme proteins, heme or its biosynthetic precursor porphyrin must be transported into mitochondria from cytosol. The mechanism of porphyrin accumulation in the mitochondrial inner membrane is unclear. In the present study, we analyzed the mechanism of mitochondrial translocation of porphyrin derivatives. We showed that palladium meso-tetra(4-carboxyphenyl)porphyrin (PdTCPP), a phosphorescent porphyrin derivative, accumulated in the mitochondria of several cell lines. Using affinity latex beads, we showed that 2-oxoglutarate carrier (OGC), the mitochondrial transporter of 2-oxoglutarate, bound to PdTCPP, and in vitro PdTCPP inhibited 2-oxoglutarate uptake into mitochondria in a competitive manner (K i ‫؍‬ 15 M). Interestingly, all types of porphyrin derivatives examined in this study competitively inhibited 2-oxoglutarate uptake into mitochondria, including protoporphyrin IX, coproporphyrin III, and hemin. Furthermore, mitochondrial accumulation of porphyrins was inhibited by 2-oxoglutarate or OGC inhibitor. These results suggested that porphyrin accumulation in mitochondria is mediated by OGC and that porphyrins are able to competitively inhibit 2-oxoglutarate uptake into mitochondria. This is the first report of a putative mechanism for accumulation of porphyrins in the mitochondrial inner membrane.Porphyrins consist of a tetrapyrrole ring structure and are most widely and efficiently used in energy metabolism. Heme (Fe-protoporphyrin IX), a porphyrin derivative, is a prosthetic molecule for several hemoproteins, and plays an essential role in various biological processes such as oxygen transport, respiration, and signal transduction. The biosynthesis of heme is a multistep process that starts with the condensation of glycineand succinyl-CoA to form 5-aminolevulinate (1). Heme is ultimately formed in the mitochondrial matrix space following translocation of the heme precursor, co-proporphyrinogen III, which is generated in cytosol, into mitochondria (1). Heme is then utilized in the mitochondrial matrix for the synthesis of a variety of heme proteins such as the cytochromes. Thus, it is necessary for heme biosynthesis and synthesis of the mitochondrial heme proteins that heme and porphyrin precursors must be transported into mitochondria from cytosol. However, the mechanism by which this mitochondrial accumulation occurs is unclear.Some metalloporphyrin derivatives are fluorescence-or phosphorescence-emitting molecules. These molecules undergo a shift from a low energy ground state to a high energy excited state upon exposure to UV light. Fluorescent or phosphorescent light is emitted as the molecules decay from their high energy state back down to the ground state. PdTCPP 3 (Fig. 1A) emits long-lived phosphorescence in respons...

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Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue

Cited by 477 publications

References 4 publications

Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation

Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation

Platinum Porphyrins as Phosphorescent Label for Time-resolved Microscopy

Porphyrin Accumulation in Mitochondria Is Mediated by 2-Oxoglutarate Carrier

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Imaging of Phosphorescence: A Novel Method for Measuring Oxygen Distribution in Perfused Tissue

Cited by 477 publications

References 4 publications

Dissociation between skeletal muscle microvascular Po2and hypoxia-induced microvascular inflammation

Dissociation between skeletal muscle microvascular Po2and hypoxia-induced microvascular inflammation

Platinum Porphyrins as Phosphorescent Label for Time-resolved Microscopy

Porphyrin Accumulation in Mitochondria Is Mediated by 2-Oxoglutarate Carrier

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Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation

Dissociation between skeletal muscle microvascular Po₂and hypoxia-induced microvascular inflammation