Impact of Calcium Quantifications on Stent Expansions

Severely calcified plaque is of great concern when planning and implementing a stenting intervention. In this work, computational models were developed to investigate the influence of calcium characteristics on stenting outcomes. The commonly used clinical measurements of calcium (i.e., the arc angle, maximum thickness, length, and volume) were varied to estimate stenting outcomes in terms of lumen gain, stent underexpansion, strut malapposition, and stress or strain distributions of the stenotic lesion. Results have shown that stenting outcomes were most sensitive to the arc angle of the calcium. A thick calcium with a large arc angle resulted in poor stenting outcomes, such as severe stent underexpansion, D-shaped lumen, increased strut malapposition, and large stresses or strains in the plaque. This was attributed to the circumferential stretch of the tissue. Specifically, the noncalcium component was stretched significantly more than the calcium. The circumferential stretch ratios of calcium and noncalcium component were approximately 1.44 and 2.35, respectively, regardless of calcium characteristics. In addition, the peak stress or strain within the artery and noncalcium component of the plaque occurred at the area adjacent to calcium edges (i.e., the interface between the calcium and the noncalcium component) coincident with the location of peak malapposition. It is worth noting that calcium played a protective role for the artery underneath, which was at the expense of the overstretch and stress concentrations in the other portion of the artery. These detailed mechanistic quantifications could be used to provide a fundamental understanding of the impact of calcium quantifications on stent expansions, as well as to exploit their potential for a better preclinical strategy.

Micromechanics of elastic lamellae: unravelling the role of structural inhomogeneity in multi-scale arterial mechanics

Microstructural deformation of elastic lamellae plays important roles in maintaining arterial tissue homeostasis and regulating vascular smooth muscle cell fate. Our study unravels the underlying microstructural origin that enables elastic lamellar layers to evenly distribute the stresses through the arterial wall caused by intraluminal distending pressure, a fundamental requirement for tissue and cellular function. A new experimental approach was developed to quantify the spatial organization and unfolding of elastic lamellar layers under pressurization in mouse carotid arteries by coupling physiological extension–inflation and multiphoton imaging. Tissue-level circumferential stretch was obtained from analysis of the deformation of a thick-walled cylinder. Our results show that the unfolding and extension of lamellar layers contribute simultaneously to tissue-level deformation. The inner lamellar layers are wavier and unfold more than the outer layers. This waviness gradient compensates the larger tissue circumferential stretch experienced at the inner surface, thus equalizing lamellar layer extension through the arterial wall. Discoveries from this study reveal the importance of structural inhomogeneity in maintaining tissue homeostasis through the arterial wall, and may have profound implications on vascular remodelling in aging and diseases, as well as in tissue engineering of functional blood vessels.

Firing patterns and functional roles of different classes of spinal afferents in rectal nerves during colonic migrating motor complexes in mouse colon

The functional role of the different classes of visceral afferents that innervate the large intestine is poorly understood. Recent evidence suggests that low-threshold, wide-dynamic-range rectal afferents play an important role in the detection and transmission of visceral pain induced by noxious colorectal distension in mice. However, it is not clear which classes of spinal afferents are activated during naturally occurring colonic motor patterns or during intense contractions of the gut smooth muscle. We developed an in vitro colorectum preparation to test how the major classes of rectal afferents are activated during spontaneous colonic migrating motor complex (CMMC) or pharmacologically induced contraction. During CMMCs, circular muscle contractions increased firing in low-threshold, wide-dynamic-range muscular afferents and muscular-mucosal afferents, which generated a mean firing rate of 1.53 ± 0.23 Hz ( n = 8) under isotonic conditions and 2.52 ± 0.36 Hz ( n = 17) under isometric conditions. These low-threshold rectal afferents were reliably activated by low levels of circumferential stretch induced by increases in length (1–2 mm) or load (1–3 g). In a small proportion of cases (5 of 34 units), some low-threshold muscular and muscular-mucosal afferents decreased their firing rate during the peak of the CMMC contractions. High-threshold afferents were never activated during spontaneous CMMC contractions or tonic contractions induced by bethanechol (100 μM). High-threshold rectal afferents were only activated by intense levels of circumferential stretch (10–20 g). These results show that, in the rectal nerves of mice, low-threshold, wide-dynamic-range muscular and muscular-mucosal afferents are excited during contraction of the circular muscle that occurs during spontaneous CMMCs. No activation of high-threshold rectal afferents was detected during CMMCs or intense contractile activity in naïve mouse colorectum.

Effects of imperfections on localized bulging in inflated membrane tubes

The problem of localized bulging in inflated membrane tubes shares the same features with a variety of other localization problems such as formation of kink bands in fibre-reinforced composites and layered structures. This type of localization is known to be very sensitive to imperfections, but the precise nature of such sensitivity has not so far been quantified. In this paper, we study effects of localized wall thinning/thickening on the onset of localized bulging in inflated membrane tubes as a prototypical example. It is shown that localized wall thinning may reduce the critical pressure or circumferential stretch by an amount of the order of the square root of maximum wall thickness reduction. As a typical example, a 10 per cent maximum wall thinning may reduce the critical circumferential stretch by 19 per cent. This square root law complements the well-known Koiter's two-thirds power law for subcritical periodic bifurcations. The relevance of our results to mathematical modelling of aneurysm formation in human arteries is also discussed.

Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity

Afferent input contributes significantly to the pain and colorectal hypersensitivity that characterize irritable bowel syndrome. In the present study, we investigated the contributions of mechanically sensitive and mechanically insensitive afferents (MIAs; or silent afferents) to colorectal hypersensitivity. The visceromotor response to colorectal distension (CRD; 15–60 mmHg) was recorded in mice before and for weeks after intracolonic treatment with zymosan or saline. After CRD tests, the distal colorectum with the pelvic nerve attached was removed for single-fiber electrophysiological recordings. Colorectal afferent endings were located by electrical stimulation and characterized as mechanosensitive or not by blunt probing, mucosal stroking, and circumferential stretch. Intracolonic zymosan produced persistent colorectal hypersensitivity (>24 days) associated with brief colorectal inflammation. Pelvic nerve muscular-mucosal but not muscular mechanosensitive afferents recorded from mice with colorectal hypersensitivity exhibited persistent sensitization. In addition, the proportion of MIAs (relative to control) was significantly reduced from 27% to 13%, whereas the proportion of serosal afferents was significantly increased from 34% to 53%, suggesting that MIAs acquired mechanosensitivity. PGP9.5 immunostaining revealed no significant loss of colorectal nerve fiber density, suggesting that the reduction in MIAs is not due to peripheral fiber loss after intracolonic zymosan. These results indicate that colorectal MIAs and sensitized muscular-mucosal afferents that respond to stretch contribute significantly to the afferent input that sustains hypersensitivity to CRD, suggesting that targeted management of colorectal afferent input could significantly reduce patients' complaints of pain and hypersensitivity.

Diameter-dependent axial prestretch of porcine coronary arteries and veins

The pressure-diameter relation (PDR) and the wall strain of coronary blood vessels have important implications for coronary blood flow and arthrosclerosis, respectively. Previous studies have shown that these mechanical quantities are significantly affected by the axial stretch of the vessels. The objective of this study was to measure the physiological axial stretch in the coronary vasculature; i.e., from left anterior descending (LAD) artery tree to coronary sinus vein and to determine its effect on the PDR and hence wall stiffness. Silicone elastomer was perfused through the LAD artery and coronary sinus trees to cast the vessels at the physiologic pressure. The results show that the physiological axial stretch exists for orders 4 to 11 (> 24 μm in diameter) arteries and orders −4 to −12 (>38 μm in diameter) veins but vanishes for the smaller vessels. Statistically, the axial stretch is higher for larger vessels and is higher for arteries than veins. The axial stretch λ z shows a linear variation with the order number ( n) as: λ z = 0.062 n + 0.75 ( R2 = 0.99) for artery and λ z = −0.029 n + 0.89 ( R2 = 0.99) for vein. The mechanical analysis shows that the axial stretch significantly affects the PDR of the larger vessels. The circumferential stretch/strain was found to be significantly higher for the epicardial arteries (orders 9–11), which are free of myocardium constraint, than the intramyocardial arteries (orders 4–8). These findings have fundamental implications for coronary blood vessel mechanics.