The Use of EPR for the Measurement of the Concentration of Oxygen in Vivo in Tissues under Physiologically Pertinent Conditions and Concentrations

Swartz, Harold M.; Boyer, Stephen J.; Brown, D.R.; Chang, Kee‐Chul; Gast, P.; Glockner, James F.; Hu, Hefei; Liu, K. J.; Moussavi, M.; Nilges, Mark J.; Norby, Shong Wan; Smirnov, Alex I.; Vahidi, N.; Walczak, Tadeusz; Wu, Meng; Clarkson, R. B.

doi:10.1007/978-1-4615-3428-0_23

Cited by 32 publications

(22 citation statements)

References 4 publications

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“…The char implantation with a sterile needle did not provoke bleeding. In the presence of oxygen, the linewidth of the EPR lines is broadened; the extent of broadening depends on pO 2 (Swartz et al, 1993;Swartz and Clarkson, 1998). The pO 2 in the region in contact with the probe was measured.…”

Section: Electron Paramagnetic Resonance Oximetrymentioning

confidence: 99%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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Electrochemotherapy has a direct cytotoxic effect on tumour cells, and presumably, a vascular disrupting effect. In this study, on the basis of the prediction of the mathematical model, histological evaluation and physiological measurements of the tumours were carried out to confirm that electroporation and electrochemotherapy of tumours have a vascular disrupting action. In the study, SA-1 solid subcutaneous sarcoma tumours in A/J mice were treated by bleomycin (BLM) given intravenously (1 mg kg À1 ), application of electric pulses (8 pulses, 1040 V, 100 ms, 1 Hz) or a combination of both -electrochemotherapy. The vascular effect was determined by laser Doppler flowmetry, power Doppler ultrasonographic imaging and Patent blue staining. The extent of tumour hypoxia was determined immunohistochemically by hypoxia marker pimonidazole and partial pressure of oxygen (pO 2 ) in tumours by electron paramagnetic resonance oximetry. Electrochemotherapy with BLM induced good antitumour effect with 22 days, tumour growth delay and 38% tumour cures. The application of electric pulses to the tumours induced instant but transient tumour blood flow reduction (for 70%) that was recovered in 24 h. During this tumour blood flow reduction, we determined an increase in hypoxic tumour area for up to 30%, which was also reflected in reduced tumour oxygenation (for 70%). According to the described mathematical model, endothelial cells lining in tumour blood vessels are exposed to a B40% higher electric field than the surrounding tumour cells, and therefore easily electroporated, allowing access of high BLM concentration to the cytosol. Consequently, electrochemotherapy has, besides the immediate vascular disrupting action, also a delayed one (after 24 h), as a consequence of endothelial cell swelling and apoptosis demonstrated by extensive tumour necrosis, tumour hypoxia, prolonged reduction of tumour blood flow and significant tumour growth delay, and tumour cures. Our results demonstrate that in addition to the well-established direct cytotoxic effect on tumour cells, electrochemotherapy also has an indirect vascular disrupting action resulting altogether in extensive tumour cell necrosis leading to complete regression of tumours.

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Section: Electron Paramagnetic Resonance Oximetrymentioning

confidence: 99%

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

et al. 2008

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“…The char implantation with a sterile needle did not provoke bleeding. In the presence of oxygen, the line-width of the EPR lines is broadened; the extent of broadening depends on pO 2 (Swartz et al, 1993;Swartz and Clarkson, 1998). The pO 2 in the region in contact with the probe was measured.…”

Section: Epr Oximetrymentioning

confidence: 99%

Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin

et al. 2002

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Electrochemotherapy is an antitumour treatment that utilises locally delivered electric pulses to increase cytotoxicity of chemotherapeutic drugs. Besides increased drug delivery, application of electric pulses affects tumour blood flow. The aim of this study was to determine tumour blood flow modifying effects of electrochemotherapy with cisplatin, its effects on tumour oxygenation and to determine their relation to antitumour effectiveness. Electrochemotherapy of SA-1 subcutaneous tumours was performed by application of electric pulses to the tumours, following administration of cisplatin. Tumour blood flow modifying effects of electrochemotherapy were determined by measurement of tumour perfusion using the Patent blue staining technique, determination of tumour blood volume, and microvascular permeability using contrast enhanced magnetic resonance imaging, and tumour oxygenation using electron paramagnetic resonance oximetry. Antitumour effectiveness was determined by tumour growth delay and the extent of tumour necrosis and apoptosis. Tumour treatment by electrochemotherapy induced 9.4 days tumour growth delay. Tumour blood flow was reduced instantaneously and persisted for several days. This reduction in tumour blood flow was reflected in reduced tumour oxygenation. The maximal reduction in partial oxygen pressure (pO 2 ) levels was observed at 2 h after the treatment, with steady recovery to the pretreatment level within 48 h. The reduced tumour blood flow and oxygenation correlated well with the extent of tumour necrosis and tumour cells apoptosis induced by electrochemotherapy with cisplatin. Therefore, the data indicate that antitumour effectiveness of electrochemotherapy is not only due to increased cytotoxicity of cisplatin due to electroporation of tumour cells, but also due to anti-vascular effect of electrochemotherapy, which resulted in reduced tumour blood flow and oxygenation.

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“…The sensitivity of d-Cat 1 and 15 N PDT to oxygen has been discussed in previous communications [9,10] and the technique of EPR oximetry has been used extensively to measure oxygen concentrations in vivo and in vitro [11,12]. The spectral linewidth and shape of these two nitroxides vary with oxygen concentration and can be calibrated accordingly [7].…”

Section: Selective Measurements Of Extracellular and Intraphagosomal mentioning

confidence: 99%

Superoxide production by phagocytosing macrophages in relation to the intracellular distribution of oxygen

James

Grinberg

Swartz

1998

Journal of Leukocyte Biology

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The Use of EPR for the Measurement of the Concentration of Oxygen in Vivo in Tissues under Physiologically Pertinent Conditions and Concentrations

Cited by 32 publications

References 4 publications

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Vascular disrupting action of electroporation and electrochemotherapy with bleomycin in murine sarcoma

Reduced blood flow and oxygenation in SA-1 tumours after electrochemotherapy with cisplatin

Superoxide production by phagocytosing macrophages in relation to the intracellular distribution of oxygen

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