Virtual reality simulation for the optimization of endovascular procedures : current perspectives

Endovascular technologies are rapidly evolving, often - requiring coordination and cooperation between clinicians and technicians from diverse specialties. These multidisciplinary interactions lead to challenges that are reflected in the high rate of errors occurring during endovascular procedures. Endovascular virtual reality (VR) simulation has evolved from simple benchtop devices to full physic simulators with advanced haptics and dynamic imaging and physiological controls. The latest developments in this field include the use of fully immersive simulated hybrid angiosuites to train whole endovascular teams in crisis resource management and novel technologies that enable practitioners to build VR simulations based on patient-specific anatomy. As our understanding of the skills, both technical and nontechnical, required for optimal endovascular performance improves, the requisite tools for objective assessment of these skills are being developed and will further enable the use of VR simulation in the training and assessment of endovascular interventionalists and their entire teams. Simulation training that allows deliberate practice without danger to patients may be key to bridging the gap between new endovascular technology and improved patient outcomes

Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is isoform-specific and disrupted by mutations underlying primary pulmonary hypertension

Diverse heterozygous mutations of bone morphogenetic receptor type II (BMPR-II) underlie the inherited form of the vascular disorder primary pulmonary hypertension (PPH). As yet, the molecular detail of how such defects contribute to the pathogenesis of PPH remains unclear. BMPR-II is a member of the transforming growth factor-beta cell signalling superfamily. Ligand binding induces cell surface receptor complex formation and activates a cascade of phosphorylation events of intracellular intermediaries termed Smads, which initiate transcriptional regulation. Some 30% of PPH-causing mutations localize to exon 12, which may be spliced out forming an isoform depleted of the unusually long BMPR-II cytoplasmic tail. To further elucidate the consequences of BMPR2 mutation, we sought to characterize aspects of the cytoplasmic domain function by seeking intracellular binding partners. We now report that Tctex-1, a light chain of the motor complex dynein, interacts with the cytoplasmic domain of BMPR-II and demonstrate that Tctex-1 is phosphorylated by BMPR-II, a function disrupted by PPH disease causing mutations within exon 12. Finally we show that BMPR-II and Tctex-1 co-localize to endothelium and smooth muscle within the media of pulmonary arterioles, key sites of vascular remodelling in PPH. Taken together, these data demonstrate a discrete function for the cytoplasmic domain of BMPR-II and justify further investigation of whether the interaction with and phosphorylation of Tctex-1 contributes to the pathogenesis of PPH

Functional interaction between BMPR-II and Tctex-1, a light chain of Dynein, is isoform-specific and disrupted by mutations underlying primary pulmonary hypertension

Diverse heterozygous mutations of bone morphogenetic receptor type II (BMPR-II) underlie the inherited form of the vascular disorder primary pulmonary hypertension (PPH). As yet, the molecular detail of how such defects contribute to the pathogenesis of PPH remains unclear. BMPR-II is a member of the transforming growth factor-b cell signalling superfamily. Ligand binding induces cell surface receptor complex formation and activates a cascade of phosphorylation events of intracellular intermediaries termed Smads, which initiate transcriptional regulation. Some 30% of PPH-causing mutations localize to exon 12, which may be spliced out forming an isoform depleted of the unusually long BMPR-II cytoplasmic tail. To further elucidate the consequences of BMPR2 mutation, we sought to characterize aspects of the cytoplasmic domain function by seeking intracellular binding partners. We now report that Tctex-1, a light chain of the motor complex dynein, interacts with the cytoplasmic domain of BMPR-II and demonstrate that Tctex-1 is phosphorylated by BMPR-II, a function disrupted by PPH disease causing mutations within exon 12. Finally we show that BMPR-II and Tctex-1 co-localize to endothelium and smooth muscle within the media of pulmonary arterioles, key sites of vascular remodelling in PPH. Taken together, these data demonstrate a discrete function for the cytoplasmic domain of BMPR-II and justify further investigation of whether the interaction with and phosphorylation of Tctex-1 contributes to the pathogenesis of PPH

Endovascular repair of ruptured abdominal aortic aneurysm: technical and team training in an immersive virtual reality environment

This study evaluates a fully immersive simulated angiosuite for training and assessment of technical endovascular and human factor skills during a crisis scenario. Virtual reality (VIST-C, Mentice) simulators were integrated into a simulated angiosuite (ORCAMP, Orzone). Teams, lead by experienced (N = 5) or trainee (N = 5) endovascular specialists, performed simulated endovascular ruptured aortic aneurysm repair (rEVAR). Timed performance metrics were recorded as surrogate measures of performance. Participants (N = 22) completed postprocedure questionnaires evaluating face validity, as well as technical and human factor aspects, of the simulation on a Likert scale from 1 (not at all) to 5 (very much). Experienced team leaders were significantly faster than trainees in obtaining proximal control with an intra-aortic occlusion balloon (352 vs. 501 s, p = 0.047) and all completed the procedure within the allotted time, whilst no trainee was able to do so. Total fluoroscopy times were significantly lower in the experienced group (782 vs. 1,086 s, p = 0.016). Realism of the simulated angiosuite was scored highly by experienced team leaders (median 4/5, IQR 4-5). Participants found the simulation useful for acquiring technical (4/5, IQR 4-5) and communication skills (4/5, IQR 4-5) and particularly valuable for enhancing teamwork (5/5, IQR 4-5) and patient safety (5/5, IQR 4-5). This study shows feasibility of creation of a crisis scenario in a fully immersive angiosuite simulation and team performance of a simulated rEVAR. Performance metrics differentiated between experienced specialists and trainees, and the realism of the simulation exercise and environment were rated highly by experienced endovascular specialists. This simulation has potential as a powerful training and assessment tool with opportunities to improve team performance in rEVAR through both technical and human factor skills training

Functional analysis of bone morphogenetic protein type II receptor mutations underlying primary pulmonary hypertension

A wide range of mutations in the type II receptor for bone morphogenetic protein (BMPR-II) have been shown to underlie primary pulmonary hypertension. To determine the mechanism of altered BMPR-II function, we employed transient transfection studies in cell lines and primary cultures of pulmonary vascular smooth muscle cells using green fluorescent protein (GFP)-tagged wild-type and mutant BMPR2 constructs and confocal microscopy to localize receptors. Substitution of cysteine residues in the ligand binding or kinase domain prevented trafficking of BMPR-II to the cell surface, and reduced binding of (125)I-BMP4. In addition, transfection of cysteine-substituted BMPR-II markedly reduced basal and BMP4-stimulated transcriptional activity of a BMP/Smad responsive luciferase reporter gene (3GC2wt-Lux), compared with wild-type BMPR-II, suggesting a dominant-negative effect of these mutants on Smad signalling. In contrast, BMPR-II containing non-cysteine substitutions in the kinase domain were localized to the cell membrane, although these also suppressed the activity of 3GC2wt-Lux. Interestingly, BMPR-II mutations within the cytoplasmic tail trafficked to the cell surface, but retained the ability to activate 3GC2wt-Lux. Transfection of mutant, but not wild-type, constructs into a mouse epithelial cell line (NMuMG cells) led to activation of p38(MAPK) and increased serum-induced proliferation compared with the wild-type receptor, which was partly p38(MAPK)-dependent. We conclude that mutations in BMPR-II heterogeneously inhibit BMP/Smad-mediated signalling by diverse molecular mechanisms. However, all mutants studied demonstrate a gain of function involving upregulation of p38(MAPK)-dependent proproliferative pathways