A Novel Experimental Method to Estimate Stress-Strain Behavior of Intact Coronary Arteries Using Intravascular Ultrasound (IVUS)

2003 ◽  
Vol 125 (1) ◽  
pp. 120-123 ◽  
Author(s):  
Azita Tajaddini ◽  
Deborah L. Kilpatrick ◽  
D. Geoffrey Vince

Most arterial mechanics studies have focused on excised non-coronary vessels, with few studies validating the application of ex-vivo results to in-vivo conditions. A method was developed for testing the mechanical properties of intact left anterior descending coronary arteries under a variety of conditions. Vascular deformation and pressure were simultaneously measured with intravascular ultrasound and a pressure transducer guidewire, respectively. Results suggest the importance of understanding in-vivo factors such as myocardial support, vascular tone and local pressure fluctuations when applying ex-vivo coronary characterization data. With further development, this method can more accurately characterize the true in-vivo constitutive behavior in normal and atherosclerotic coronaries.

2008 ◽  
Vol 101 (8) ◽  
pp. 1079-1083 ◽  
Author(s):  
Kenya Nasu ◽  
Etsuo Tsuchikane ◽  
Osamu Katoh ◽  
D. Geoffrey Vince ◽  
Pauliina M. Margolis ◽  
...  

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Gentian Lluri ◽  
Xiaoqian Liu ◽  
Atsushi N

Objective: We examined whether the hematopoietic cells induce the coronary artery formation using genetically modified mouse models of hematopoietic ablation in vivo and ex vivo . Methods: As a model of for hematopoietic cell deficient animals, we used Runx1 (a transcription factor required for definitive hematopoiesis) knockout embryos and Vav1-cre; R26-DTA embryos, which ablates 2/3 of CD45+ hematopoietic cells. The coronary growth and the hematopoietic cells were evaluated in whole-mount, section and ex vivo explant culture. Results: The developing coronary endothelial cells form blood-island-like structure at around E12.5 in the subepicardial region. Interestingly, however, the histological analyses suggest that the first Ter119+ and CD45+ blood cells appear in the subendocardial area at E10.5, even before the formation of coronary channels. These initial hematopoietic cells in the heart are not likely derived from the epicardium, as the sorted epicardial cells yielded no hematopoietic cell in colony formation assay. These observations raised a question whether these heart-resident hematopoietic cells rather play an inductive role during coronary formation. To examine this possibility, we analyzed two hematopoietic ablation models. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 knockout embryos and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Conclusion: Hematopoietic cells are not merely transported via coronary vessels, but substantially involved in the induction of the coronary vessels during cardiogenesis.


2000 ◽  
Vol 83 (05) ◽  
pp. 752-758 ◽  
Author(s):  
Claude Le Feuvre ◽  
Annie Brunet ◽  
Thuc Do Pham ◽  
Jean-Philippe Metzger ◽  
André Vacheron ◽  
...  

SummaryThe 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O2−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca2+ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelets by decreasing Ca2+ influx. It attenuated Ca2+ mobilization from internal stores evoked by thrombin or thapsigargin. In vitro studies were used as an approach to investigate how simultaneous productions of NO and O2− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca2+ mobilization. Superoxide dismutase, the O2− scavenger, enhanced the capacity of SIN-1 to inhibit Ca2+ mobilization but catalase had no effect.This suggests that the effects of SIN-1 on platelet Ca2+ handling resemble those of NO, but are modulated by simultaneous O2− release, independently of H2O2 formation.


2002 ◽  
Vol 124 (6) ◽  
pp. 734-741 ◽  
Author(s):  
Alexander I. Veress ◽  
Jeffrey A. Weiss ◽  
Grant T. Gullberg ◽  
D. Geoffrey Vince ◽  
Richard D. Rabbitt

Atherosclerotic plaque rupture is responsible for the majority of myocardial infarctions and acute coronary syndromes. Rupture is initiated by mechanical failure of the plaque cap, and thus study of the deformation of the plaque in the artery can elucidate the events that lead to myocardial infarction. Intravascular ultrasound (IVUS) provides high resolution in vitro and in vivo cross-sectional images of blood vessels. To extract the deformation field from sequences of IVUS images, a registration process must be performed to correlate material points between image pairs. The objective of this study was to determine the efficacy of an image registration technique termed Warping to determine strains in plaques and coronary arteries from paired IVUS images representing two different states of deformation. The Warping technique uses pointwise differences in pixel intensities between image pairs to generate a distributed body force that acts to deform a finite element model. The strain distribution estimated by image-based Warping showed excellent agreement with a known forward finite element solution, representing the gold standard, from which the displaced image was created. The Warping technique had a low sensitivity to changes in material parameters or material model and had a low dependency on the noise present in the images. The Warping analysis was also able to produce accurate strain distributions when the constitutive model used for the Warping analysis and the forward analysis was different. The results of this study demonstrate that Warping in conjunction with in vivo IVUS imaging will determine the change in the strain distribution resulting from physiological loading and may be useful as a diagnostic tool for predicting the likelihood of plaque rupture through the determination of the relative stiffness of the plaque constituents.


2018 ◽  
Author(s):  
Pinar Akcakaya ◽  
Maggie L. Bobbin ◽  
Jimmy A. Guo ◽  
Jose M. Lopez ◽  
M. Kendell Clement ◽  
...  

CRISPR-Cas genome-editing nucleases hold substantial promise for human therapeutics1–5 but identifying unwanted off-target mutations remains an important requirement for clinical translation6, 7. For ex vivo therapeutic applications, previously published cell-based genome-wide methods provide potentially useful strategies to identify and quantify these off-target mutation sites8–12. However, a well-validated method that can reliably identify off-targets in vivo has not been described to date, leaving the question of whether and how frequently these types of mutations occur. Here we describe Verification of In Vivo Off-targets (VIVO), a highly sensitive, unbiased, and generalizable strategy that we show can robustly identify genome-wide CRISPR-Cas nuclease off-target effects in vivo. To our knowledge, these studies provide the first demonstration that CRISPR-Cas nucleases can induce substantial off-target mutations in vivo, a result we obtained using a deliberately promiscuous guide RNA (gRNA). More importantly, we used VIVO to show that appropriately designed gRNAs can direct efficient in vivo editing without inducing detectable off-target mutations. Our findings provide strong support for and should encourage further development of in vivo genome editing therapeutic strategies.


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