K+ channels in the coronary microvasculature of the ischemic heart.

Ischemic heart disease is the leading cause of death and a major public health and economic burden worldwide with expectations of predicted growth in the foreseeable future. It is now recognized clinically that flow-limiting stenosis of the large coronary conduit arteries as well as microvascular dysfunction in the absence of severe stenosis can each contribute to the etiology of ischemic heart disease. The primary site of coronary vascular resistance, and control of subsequent coronary blood flow, is found in the coronary microvasculature, where small changes in radius can have profound impacts on myocardial perfusion. Basal active tone and responses to vasodilators and vasoconstrictors are paramount in the regulation of coronary blood flow and adaptations in signaling associated with ion channels are a major factor in determining alterations in vascular resistance and thereby myocardial blood flow. K+ channels are of particular importance as contributors to all aspects of the regulation of arteriole resistance and control of perfusion into the myocardium because these channels dictate membrane potential, the resultant activity of voltage-gated calcium channels, and thereby, the contractile state of smooth muscle. Evidence also suggests that K+ channels play a significant role in adaptations with cardiovascular disease states. In this review, we highlight our research examining the role of K+ channels in ischemic heart disease and adaptations with exercise training as treatment, as well as how our findings have contributed to this area of study.

Diffusible contrast-enhanced micro-CT improves visualization of stented vessels.

In this report, we showcase diffusible iodine-based contrast-enhanced computed tomography (DICE-CT) as a method for improving soft tissue visualization and reducing beam hardening artifact within a stented vessel. This technique is commonly used in our pathology lab to image soft tissue specimens with dense metal implants and to ensure reliable morphological analysis through clear delineation of tissue structures. For this report, a porcine right coronary artery with an implanted metal stent was scanned using both conventional and DICE-CT methods. Upon reconstruction, DICE-CT produced less beam hardening artifact in comparison to traditional micro-CT; furthermore, DICE-CT produced results with morphometric similarity to histology. Accordingly, these differences illustrated the clear advantage of using DICE-CT over conventional micro-CT when imaging soft tissue specimens with dense metal implants.

Iodine-based contrast staining improves micro-computed tomography of atherosclerotic coronary arteries.

We sought to develop a reversible staining protocol using micro-computed tomography (micro-CT) paired with a radiopaque contrast agent that allows for three-dimensional in situ visualization and characterization of atherosclerotic plaques. Atherosclerotic porcine coronary arteries were dissected from surrounding myocardium and incubated in iohexol at various concentrations and incubation times and then imaged using direct radiography. Line profiles were generated across the artery x-ray to determine effectiveness of the radiopaque contrast agent to penetrate the tissue. Our studies revealed that, to sufficiently delineate tissue constructs, the minimum effective iohexol concentration and incubation time were 240 mgI/mL for 1 hour. Among all groups, 24 hours of de-staining brought radiopacity back to control levels. After iohexol incubation, micro-CT was performed. Our findings demonstrate that extended staining times and a minimum iohexol concentration of 240 mgI/mL are required for effective tissue perfusion, which eliminates the diffusion distribution profile inherent to the ability of the contrast agent to traverse tissue layers.•Iohexol enhances ex vivo micro-CT imaging of atherosclerotic coronary arteries•Iohexol allows for improved tissue segmentation during micro-CT image analysis•Effectiveness of iohexol penetration of the tissue was dependent on concentration and duration of incubation.

Iodine-enhanced micro-computed tomography of atherosclerotic plaque morphology complements conventional histology.

BACKGROUND AND AIMS: Visualization of arterial lesions in situ can enhance understanding of atherosclerosis progression and potentially improve experimental therapies. Conventional histology methods for assessing atherosclerotic lesions are robust but are destructive and may prevent further tissue analysis. The objective of the current study was to evaluate a novel, nondestructive method for visualization and characterization of atherosclerotic lesions as an alternative or complementary to routine histology. Thus, we tested the hypothesis that micro-computed tomography (micro-CT) paired with an iodine-based radiopaque stain would effectively characterize atherosclerotic plaques in a manner comparable to routine histology while maintaining sample integrity and providing whole-volume data. METHODS: We examined porcine coronary arteries with varying degrees of atherosclerosis, using micro-CT in the absence and presence of iohexol (240 mgI/ml). Following iohexol washout, routine histological assessment of the samples was performed with hematoxylin and eosin and Masson's trichrome. RESULTS: Iohexol staining generated soft tissue delineation and subsequent atherosclerotic plaque assessment via augmented radiopacity, permitting three-dimensional (3D) reconstruction of these lesions, maintaining in situ architecture. Although plaque distribution and arterial wall tissue layers were discernible, micro-CT was incapable of discriminating cell types comprising the plaque. Calcium phosphate deposition was readily located and visualized in 3D space, independent of iohexol. CONCLUSIONS: The results of this study establish micro-CT, combined with a diffusible radiopaque contrast agent, as a powerful imaging modality for visualizing in situ architecture of atherosclerotic plaques. Our findings demonstrate that micro-CT can be used to identify plaque distribution and calcium deposition complementary to routine histological analysis.