| Effect of graded hypoxia on retention of technetium-99m-nitroheterocycle in perfused rat heart. | |
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MedLine Citation:
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PMID: 7699458 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The purpose of this investigation was to determine the effects of graded hypoxia on the retention of a 99mTc-labeled nitroimidazole. METHODS: Rat hearts were perfused retrogradely with Krebs-Henseleit buffer at 37 degrees C and paced at 5 Hz. After a 20-min stabilization period, coronary flow was maintained at 8 ml/min/g wet wt and the hearts were perfused with media equilibrated with gas mixtures containing 5% CO2 and various levels of O2, from 544 to 29 Torr. Technetium-99m-O(PnAO-1-(2-nitroimidazole)), BMS-181321, was infused for 20 min into a side port of the aortic cannula. Perfusion continued for an additional 40 min to allow for compound clearance. RESULTS: Each decrease of perfusate PO2 brought about an increase in the retention of BMS-181321, resulting in a good correlation between its retention and perfusate PO2 (r = 0.97). Myocardial oxygen consumption was independent of oxygen delivery when the perfusate oxygen pressure was greater than 350 Torr. Below this value, oxygen consumption declined markedly as influent PO2 was decreased. By contrast, the tissue lactate/pyruvate ratio and lactate efflux rose with each decrease of influent PO2. A good correlation was obtained between retention of the nitroheterocycle and the cytosolic lactate/pyruvate ratio (r = 0.98). When glucose was omitted from the perfusate (PO2 = 27 Torr), retention of the nitroheterocycle was increased by about 25% as compared to hearts perfused in the presence of this substrate. CONCLUSION: These results indicate that myocardial retention of BMS-181321 is coupled to the level of tissue oxygenation and that hypoxic retention may be affected by substrate input. |
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Authors:
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W L Rumsey; B Patel; K E Linder |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of nuclear medicine : official publication, Society of Nuclear Medicine Volume: 36 ISSN: 0161-5505 ISO Abbreviation: J. Nucl. Med. Publication Date: 1995 Apr |
Date Detail:
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Created Date: 1995-05-04 Completed Date: 1995-05-04 Revised Date: 2003-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 632-6 Citation Subset: IM |
Affiliation:
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Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Hypoxia / physiology Heart / radionuclide imaging* Male Myocardium / metabolism Nitroimidazoles / diagnostic use*, pharmacokinetics Organotechnetium Compounds / diagnostic use*, pharmacokinetics Oxygen Consumption Perfusion Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Nitroimidazoles; 0/Organotechnetium Compounds; 149447-21-2/BMS 181321 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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