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

Abstract

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<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 PO 2 .

Impaired skeletal muscle performance as a consequence of random functional capillary rarefaction can be restored with overload‐dependent angiogenesis

“…The strong relationship between muscle fatigue resistance and functional (perfused) capillaries (Fig. 4C) is indicative of the critical function of the microcirculation, as also observed in cardiac muscle (Hauton et al 2015). Our findings may be particularly relevant to the development of heart failure, where the magnitude of capillary rarefaction in skeletal muscle progressively increases with time after experimental induction of the condition (Nusz et al 2003), and where the decline in fatigue resistance depends upon clinical severity (Buller et al 1991).…”

“…4) is indicative of the critical function of the microcirculation, as also observed in cardiac muscle (Hauton et al . 2015). Our findings may be particularly relevant to the development of heart failure, where the magnitude of capillary rarefaction in skeletal muscle progressively increases with time after experimental induction of the condition (Nusz et al .…”

“…4) indicates that skeletal muscle is sensitive to small perturbations in the microcirculation, although to a lesser extent than cardiac muscle (Hauton et al . 2015), which has a correspondingly highly oxidative metabolic phenotype (De Sousa et al . 2002).…”

“…Interestingly, the relationship between FI and functional capillary density (Fig. 4) indicates that skeletal muscle is sensitive to small perturbations in the microcirculation, although to a lesser extent than cardiac muscle (Hauton et al 2015), which has a correspondingly highly oxidative metabolic phenotype (De Sousa et al 2002). This suggests that there is little functional reserve in the capillary bed, i.e.…”

“…In support of this, an ∼4‐fold reduction in mechanical output of the heart resulted from a stochastic occlusion of 25% of terminal arterioles in the coronary microcirculation, suggesting that distributive (microvascular) ischaemia may be more detrimental than that with a focal (arterial) origin (Hauton et al . 2015). Thus, microvascular rarefaction per se may represent a mechanism for exercise intolerance associated with diseases adversely affecting the microcirculation (e.g.…”