Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply

Research output: Contribution to journalArticle

Authors

  • David Hauton
  • Abdullah A Al-Shammari
  • Eamonn A Gaffney
  • Rhys D Evans
  • Stuart Egginton

Colleges, School and Institutes

External organisations

  • University of Leeds
  • Mathematical Institute, University of Oxford, Woodstock Road, Oxford OX2 6GG, United Kingdom; Department of Mathematics, Faculty of Sciences, Kuwait University, P.O. Box 5969, Khaldiya 13060, Kuwait.
  • Mathematical Institute, University of Oxford, Woodstock Road, Oxford OX2 6GG, United Kingdom.
  • Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, South Parks Road, Oxford OX1 3PT, United Kingdom.

Abstract

BACKGROUND: The relative importance of arteriole supply or ability to switch between substrates to preserve cardiac performance is currently unclear, but may be critically important in conditions such as diabetes.

METHODS: Metabolism of substrates was measured before and after infusion of polystyrene microspheres in the perfused working heart to mimic random capillary loss due to microvascular disease. The effect of acute loss of functional capillary supply on palmitate and glucose metabolism together with function was quantified, and theoretical tissue oxygen distribution calculated from histological samples and ventricular VO(2) estimated.

RESULTS: Microsphere infusion led to a dose-dependent decrease in rate-pressure product (RPP) and oxygen consumption (P<0.001). Microsphere infusion also increased work/unit oxygen consumption of hearts ('efficiency') by 25% (P<0.01). When corrected for cardiac work palmitate oxidation remained tightly coupled to very low workloads (RPP<2500 mmHg/min), illustrating a high degree of metabolic control. Arteriole occlusion by microspheres decreased the density of patent capillaries (P<0.001) and correspondingly increased the average capillary supply area by 40% (P<0.01). Calculated rates of oxygen consumption declined from 16.6±7.2 ml/100 ml/min to 12.4±9 ml/100 ml/min following arteriole occlusion, coupled with increases in size of regions of myocardial hypoxia (Control=22.0% vs. Microspheres=42.2%).

CONCLUSIONS: Cardiac mechanical performance is very sensitive to arteriolar blockade, but metabolite switching from fatty acid to glucose utilisation may also support cardiac function in regions of declining PO(2).

GENERAL SIGNIFICANCE: Preserving functional capillary supply may be critical for maintenance of cardiac function when metabolic flexibility is lost, as in diabetes.

Details

Original languageEnglish
Pages (from-to)681-90
Number of pages10
JournalBiochimica et Biophysica Acta
Volume1850
Issue number4
Publication statusPublished - Apr 2015

Keywords

  • Acetyl Coenzyme A, Animals, Capillaries, Coronary Circulation, Glucose, Male, Microspheres, Myocardium, Oxygen Consumption, Palmitates, Rats, Rats, Wistar, Journal Article, Research Support, Non-U.S. Gov't