Slackness between vessel and myocardium is necessary for coronary flow reserve

Tone regulation in coronary microvessels has largely been studied in isolated vessels in the absence of myocardial tethering. Here, the potential effect of radial tethering and interstitial space connective tissue (ISCT) between coronary microvessels and the surrounding myocardium was studied. We hypothesized that rigid tethering between microvessels and the myocardium would constrain the active contraction of arterioles and is not compatible with the observed tone regulation. The ISCT between coronary microvessels and myocardium in five swine was found to increase exponentially from 0.22 ± 0.02 μm in capillaries (modified Strahler order 0) of the endocardium to 34.9 ± 7.1 μm in epicardial vessels (order 10). Microvessels with both soft tethering and ISCT gap were capable of significant changes in vessel resistance (up to an ∼1,600% increase), consistent with experimental measurements of high coronary flow reserve. Additionally, the mechanical energy required for myogenic contraction was estimated. The results indicate that rigid tethering requires up to four times more mechanical energy than soft tethering in the absence of a gap. Hence, the experimental measurements and model predictions suggest that effectiveness and efficiency in tone regulation can be achieved only if the vessel is both softly tethered to and separated from the myocardium in accordance with the experimental findings of ISCT gap. These results have fundamental implications on future simulations of coronary circulation.