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Local metabolic hypothesis is not sufficient to explain coronary autoregulatory behavior

Basic Research in Cardiology volume 113, Article number: 33 (2018) Cite this article

An Invited Editorial to this article was published on 03 August 2018

Abstract

The local metabolic hypothesis proposes that myocardial oxygen tension determines the degree of autoregulation by increasing the production of vasodilator metabolites as perfusion pressure is reduced. Thus, normal physiologic levels of coronary venous PO2, an index of myocardial oxygenation, are proposed to be required for effective autoregulation. The present study challenged this hypothesis through determination of coronary responses to changes in coronary perfusion pressure (CPP 140–40 mmHg) in open-chest swine in the absence (n = 7) and presence of euvolemic hemodilution (~ 50% reduction in hematocrit), with (n = 5) and without (n = 6) infusion of dobutamine to augment MVO2. Coronary venous PO2 decreased over similar ranges (~ 28–15 mmHg) as CPP was lowered from 140 to 40 mmHg in each of the groups. However, coronary venous PO2 was not associated with changes in coronary blood flow (r = − 0.11; P = 0.29) or autoregulatory gain (r = − 0.29; P = 0.12). Coronary zero-flow pressure (Pzf) was measured in 20 mmHg increments and determined to be directly related to vascular resistance (r = 0.71; P < 0.001). Further analysis demonstrated that changes in coronary blood flow remained minimal at Pzf > 20 mmHg, but progressively increased as Pzf decreased below this threshold value (r = 0.68; P < 0.001). Coronary Pzf was also positively correlated with autoregulatory gain (r = 0.43; P = 0.001). These findings support that coronary autoregulatory behavior is predominantly dependent on an adequate degree of underlying vasomotor tone, independent of normal myocardial oxygen tension.

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Acknowledgements

The authors wish to thank Joshua Sturek for expert technical assistance. This study was supported by the National Institutes of Health U01HL118738.

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Affiliations

  1. Department of Cellular and Integrative Physiology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN, 46202, USA

    Alexander M. Kiel, Adam G. Goodwill, Hana E. Baker & Johnathan D. Tune

  2. Weldon School of Biomedical Engineering, Purdue University, 206 S Martin Jischke Dr, West Lafayette, IN, 47907, USA

    Alexander M. Kiel

  3. California Medical Innovations Institute, 11107 Roselle Street, San Diego, CA, 92121, USA

    Gregory M. Dick

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  1. Alexander M. Kiel
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Correspondence to Johnathan D. Tune.

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Kiel, A.M., Goodwill, A.G., Baker, H.E. et al. Local metabolic hypothesis is not sufficient to explain coronary autoregulatory behavior. Basic Res Cardiol 113, 33 (2018). https://doi.org/10.1007/s00395-018-0691-0

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  • DOI: https://doi.org/10.1007/s00395-018-0691-0

Keywords

  • Coronary
  • Autoregulation
  • Zero-flow pressure
  • Swine