Citations

Background— Little is known about the clinical value of stress imaging studies in asymptomatic patients after percutaneous coronary intervention (PCI). Methods and Results— Residents of Olmsted County, MN, who underwent PCI were followed up for the occurrence of stress imaging (stress nuclear or stress echocardiography), coronary angiography, or coronary artery bypass grafting (without angiography) as initial procedures after PCI. Patients whose first follow-up procedure was a stress imaging test were evaluated for their symptom status at the time of the study and whether they underwent angiography or revascularization (PCI or coronary artery bypass grafting) within 90 days. Of 1848 patients who underwent PCI during the study period, 710 (38%) had stress imaging as their initial procedure after PCI, and 241 (13% of the entire cohort) were asymptomatic at the time of testing. The majority (86%) of these 241 patients underwent PCI for acute myocardial infarction or unstable angina. Within 90 days of stress imaging, 16 of the 241 asymptomatic patients underwent angiography, and 2 patients were revascularized. Stratified by timing after PCI, none of 138 asymptomatic patients tested within 2 years of PCI underwent revascularization. Two of 103 asymptomatic patients tested after 2 years from PCI underwent revascularization. Compared with patients who were asymptomatic at the time of stress imaging, patients who did not undergo any follow-up procedures (stress imaging, angiography, or coronary artery bypass grafting) after the index PCI were older, were more likely to have comorbidities, and had significantly greater all-cause mortality ( P <0.001). Conclusions— In a population-based sample of patients undergoing PCI primarily for acute coronary syndromes, 1 in 8 had subsequent stress imaging when they were asymptomatic. These stress imaging tests resulted in further revascularization in <1% of patients. The low rate of downstream revascularization suggests that stress imaging in asymptomatic patients after PCI has low value.

Interstitial cells of Cajal (ICC) act as pacemaker cells in the gastrointestinal tract by generating electrical slow waves to regulate rhythmic smooth muscle contractions. Intrinsic Ca 2+ oscillations in ICC appear to produce the slow waves by activating pacemaker currents, currently thought to be carried by the Ca 2+ -activated Cl − channel anoctamin 1 (Ano1). In this article we present a novel model of small intestinal ICC pacemaker activity that incorporates store-operated Ca 2+ entry and a new model of Ano1 current. A series of simulations were carried out with the ICC model to investigate current controversies about the reversal potential of the Ano1 Cl − current in ICC and to predict the characteristics of the other ion channels that are necessary to generate slow waves. The model results show that Ano1 is a plausible pacemaker channel when coupled to a store-operated Ca 2+ channel but suggest that small cyclical depolarizations may still occur in ICC in Ano1 knockout mice. The results predict that voltage-dependent Ca 2+ current is likely to be negligible during the slow wave plateau phase. The model shows that the Cl − equilibrium potential is an important modulator of slow wave morphology, highlighting the need for a better understanding of Cl − dynamics in ICC.

Depletion of interstitial cells of Cajal (ICC) networks is known to occur in several gastrointestinal motility disorders. Although confocal microscopy can effectively image and visualize the spatial distribution of ICC networks, current descriptors of ICC depletion are limited to cell numbers and volume computations. Spatial changes in ICC network structural properties have not been quantified. Given that ICC generate electrical signals, the organization of a network may also affect physiology. In this study, six numerical metrics were formulated to automatically determine complex ICC network structural properties from confocal images: density , thickness , hole size , contact ratio , connectivity and anisotropy . These metrics were validated and applied in proof-of-concept studies to quantitatively determine jejunal ICC network changes in mouse models with decreased ( 5-HT 2 B receptor knockout (KO)) and normal ( Ano1 KO) ICC numbers, and during post-natal network maturation. Results revealed a novel remodelling phenomenon occurring during ICC depletion, namely a spatial rearrangement of ICC and the preferential longitudinal alignment. In the post-natal networks, an apparent pruning of the ICC network was demonstrated. The metrics developed here enabled the first detailed quantitative analyses of structural changes that may occur in ICC networks during depletion and development.

Smooth muscle exhibits mechanosensitivity independent of neural input, suggesting that mechanosensitive pathways reside within smooth muscle cells. The native L-type calcium current recorded from human intestinal smooth muscle is modulated by stretch. To define mechanosensitive mechanisms involved in the regulation of smooth muscle calcium entry, we cloned the α1C L-type calcium channel subunit (CaV1.2) from human intestinal smooth muscle and expressed the channel in a heterologous system. This channel subunit retained mechanosensitivity when expressed alone or coexpressed with a β2 calcium channel subunit in HEK-293 or Chinese hamster ovary cells. The heterologously expressed human cardiac α1C splice form also demonstrated mechanosensitivity. Inhibition of kinase signaling did not affect mechanosensitivity of the native channel. Truncation of the α1C COOH terminus, which contains an inhibitory domain and a proline-rich domain thought to mediate mechanosensitive signaling from integrins, did not disrupt mechanosensitivity of the expressed channel. These data demonstrate mechanical regulation of calcium entry through molecularly identified L-type calcium channels in mammalian cells and suggest that the mechanosensitivity resides within the pore forming α1C-subunit.