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      Control of Coronary Flow by Local Factors during Hypoxia with and without a Fall in O 2 Consumption

      Journal of Vascular Research

      S. Karger AG

      Adenosine, Adenosine deaminase, Bioassay, Guinea pig, Metabolic regulation, Theophylline

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          Abstract

          The primary objectives were: (1) to examine if vasodilatory amounts of metabolites are released during moderate as well as during severe hypoxia of donor hearts; (2) to compare vasodilation to hypoxia with infusion of adenosine, and (3) to determine if metabolically induced vasodilation can be selectively reduced or abolished in order to determine the responsible metabolic factors. Pairs of isolated guinea pig hearts (n = 50) were perfused with a modified physiological saline solution by the Langendorff method. Assay hearts were also perfused with either uncorrected, anaerobic donor heart effluent or with effluent in which Po<sub>2</sub>, Pco<sub>2</sub> and pH were corrected to control perfusate levels. When donor hearts were made moderately hypoxic (effluent Po<sub>2</sub> – 45 ± 5 Torr; myocardial oxygen consumption – MVO<sub>2</sub>-unchanged) and assay hearts were perfused at constant pressure with gas-corrected donor effluent, we saw no change in assay flow. But when adenosine was infused to produce the same flow increase observed during mild hypoxia in donor hearts, the assay heart conductance rose to 38 ± 7%. In contrast, when donor hearts were made severely hypoxic (effluent Po<sub>2</sub> = 34 ± Torr; MVO<sub>2</sub> reduced by 53 ± 6% and assay hearts were perfused at constant flow with corrected donor effluent), we found a 60 ± 5 % increase in vascular conductance; this dropped to 24 ± 6% over control when adenosine deaminase was infused into the donor effluent tubing and to 5 ± 4% when theophylline was infused into assay hearts. In this bioassay study we also found that 68 ± 5% of adenosine infused into donor hearts during normoxia was removed in transit through the vasculature. Overall, our results indicate that adenosine, primarily, but perhaps also adenine nucleotides, are released in vasodilatory concentrations with severe hypoxia. However, the metabolic factors which increase coronary flow during mild hypoxia when MVO<sub>2</sub> is not compromised could not be ascertained.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          1982
          1982
          19 September 2008
          : 19
          : 3
          : 148-164
          Affiliations
          Department of Physiology, The Medical College of Wisconsin, Milwaukee Regional Medical Center, Milwaukee, Wisc., USA
          Article
          158381 Blood Vessels 1982;19:148–164
          10.1159/000158381
          © 1982 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 17
          Categories
          Research Paper

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