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

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 VO2 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<2,500 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/100ml/min to 12.4 ± 9 ml/100ml/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 PO2. GENERAL SIGNIFICANCE: Preserving functional capillary supply may be critical for maintenance of cardiac function when metabolic flexibility is lost, as in diabetes.