title: Changes to both cardiac metabolism and performance accompany acute reductions in functional capillary supply.
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).
  
  
  CONCLUSIONS
  Preserving functional capillary supply may be critical for maintenance of cardiac function when metabolic flexibility is lost, as in diabetes.
authors.affiliation: School of Food Science and Nutrition, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, United Kingdom. Electronic address: d.hauton@leeds.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Hauton
authors.affiliation: Cardiovascular Physiology, The Rayne Institute, King's College London, London SE1 7EH, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Winter
authors.affiliation: 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.
authors.forename: Abdullah A
authors.initials: AA
authors.lastname: Al-Shammari
authors.affiliation: Mathematical Institute, University of Oxford, Woodstock Road, Oxford OX2 6GG, United Kingdom.
authors.forename: Eamonn A
authors.initials: EA
authors.lastname: Gaffney
authors.affiliation: Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, South Parks Road, Oxford OX1 3PT, United Kingdom.
authors.forename: Rhys D
authors.initials: RD
authors.lastname: Evans
authors.affiliation: School of Biomedical Sciences, University of Leeds, Clarendon Way, Leeds LS2 9JT, United Kingdom.
authors.forename: Stuart
authors.initials: S
authors.lastname: Egginton
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D002196:Capillaries / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D008297:Male; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010168:Palmitates; D000105:Acetyl Coenzyme A; D005947:Glucose
keywords: Arteriole occlusion; Capillary domain; Cardiac performance; Metabolism; Microspheres; Working heart