Transmural alterations in coronary artery biomechanics in heart failure: Implications for microvascular therapeutic targeting

Abstract It has been suggested that there are transmural differences in the structure and function of arteries in the left ventricle. For example, for arteries of the same diameter, wall thickness may be greater in vessels of the epicardium than those from the endocardium. It has been speculated that such transmural differences could influence myogenic reactivity and coronary flow regulation. Variations in structure would suggest potential differences in passive and active length-tension relationships of arteries, as different amounts of connective tissue or smooth muscle would be expected to alter characteristics. We tested the hypothesis that coronary artery length-tension properties vary transmurally (i.e., epicardium vs. endocardium) in the porcine left ventricle. Further, because heart failure involves tissue remodeling and alters biomechanical properties, we examined the effect of pacing-induced heart failure on the coronary artery length-tension relationship in swine. Isometric tension properties were determined by wire myography, while structural features were determined histologically. There was no difference in the active or passive length-tension curves of equally sized epicardial and endocardial arteries from the normal heart. In contrast, pacing-induced heart failure increased the passive tension at optimal length in endocardial arteries and increased the active tension in epicardial arteries. Our results represent the first comparison of transmural differences in coronary arteries under isometric tension. The findings support that pacing-induced heart failure alters the biomechanical properties of small coronary arteries. Because arterial stiffness and contractility are therapeutic targets in heart failure, it may be important to further study direct vascular effects of approved drugs like sodium-glucose cotransporter-2 inhibitors and mineralocorticoid receptor blockers.