Decreased PGC-1α Post-Cardiopulmonary Bypass Leads to Impaired Oxidative Stress in Diabetic Patients.

BACKGROUND: The mechanism of mitochondrial dysfunction after cardiopulmonary bypass (CPB) in patients with diabetes mellitus lacks understanding. We hypothesized that impaired beta-oxidation of fatty acids leads to worsened stress response in this patient population after cardiac surgery. METHODS: After Institutional Review Board approval, right atrial tissue samples were collected from 35 diabetic patients and 33 nondiabetic patients before and after CPB. Patients with glycated hemoglobin of 6.0 or greater and a clinical diagnosis of diabetes mellitus were considered to be diabetic. Immunoblotting and microarray analysis were performed to assess protein and gene expression changes. Blots were quantified with ImageJ and analyzed using one-way analysis of variance with multiple Student's t test comparisons after normalization. All p values less than 0.05 were considered significant. Immunohistochemistry was performed for cellular lipid deposition assessment. RESULTS: Diabetic patients had significantly lower levels of PGC-1α before and after CPB (p < 0.01 for both) compared with nondiabetic patients. Several upstream regulators of PGC-1α (SIRT1 and CREB) were significantly higher in nondiabetic patients before CPB (p = 0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic factors (TGF-ß, NT3, and Ang1), and the antiapoptotic factor BCL-xL were significantly lower in diabetic patients after CPB (p < 0.05). The expression of genes supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic genes (p < 0.05) was significantly downregulated in diabetic patients after CPB. Immunohistochemistry results showed significantly increased lipid deposition in diabetic myocardial tissue. CONCLUSIONS: Decreased PGC-1α in diabetic patients may lead to impaired mitochondrial function and attenuated antiapoptotic and angiogenic responses after CPB. Therefore, PGC-1α and upstream regulators could serve as a target for improving beta-oxidation in diabetic patients.

Improving Clinical Proficiency Using a 3-Dimensionally Printed and Patient-Specific Thoracic Spine Model as a Haptic Task Trainer.

BACKGROUND AND OBJECTIVES: Advanced haptic simulators for neuraxial training are expensive, have a finite life, and are not patient specific. We sought to demonstrate the feasibility of developing a custom-made, low-cost, 3-dimensionally printed thoracic spine simulator model from patient computed tomographic scan data. This study assessed the model's practicality, efficiency as a teaching tool, and the transfer of skill set into patient care. METHODS: A high-fidelity, patient-specific thoracic spine model was used for the study. Thirteen residents underwent a 1-hour 30-minute training session prior to performing thoracic epidural analgesia (TEA) on patients. We observed another group of 14 residents who were exposed to the traditional method of training during their regional anesthesia rotation for thoracic epidural placement. The TEA was placed for patients under the supervision of attending anesthesiologists, who were blinded to the composition of the study and control groups. As a primary outcome, data were collected on successful TEAs, which was defined as a TEA that provided full relief of sensation across the entire surgical area as assessed by both a pinprick and temperature test. Secondary outcomes included whether any assistance from the attending physician was required and failed epidurals. RESULTS: A total of 27 residents completed the study (14 in the traditional training, 13 in the study group). We found that the residents who underwent training with the simulator had a significantly higher success rate (11 vs 4 successful epidural attempts, P = 0.002) as compared with the traditional training group. The control group also required significantly more assistance from the supervising anesthesiologist compared with the study group (5 vs 1 attempt requiring guidance). The number needed to treat (NNT) for the traditional training group was 1.58 patients over the study period with a 95% confidence interval of 1.55 to 1.61. CONCLUSIONS: By using patient-specific, 3-dimensionally printed, thoracic spine models, we demonstrated a significant improvement in clinical proficiency as compared with traditional teaching models.

Low-cost three-dimensional printed phantom for neuraxial anesthesia training: Development and comparison to a commercial model.

METHODS: Anonymized CT DICOM data was segmented to create a 3D model of the lumbar spine. The 3D model was modified, placed inside a digitally designed housing unit and fabricated on a desktop 3D printer using polylactic acid (PLA) filament. The model was filled with an echogenic solution of gelatin with psyllium fiber. Twenty-two staff anesthesiologists performed a spinal and epidural on the 3D printed simulator and a commercially available Simulab phantom. Participants evaluated the tactile and ultrasound imaging fidelity of both phantoms via Likert-scale questionnaire. RESULTS: The 3D printed neuraxial phantom cost $13 to print and required 25 hours of non-supervised printing and 2 hours of assembly time. The 3D printed phantom was found to be less realistic to surface palpation than the Simulab phantom due to fragility of the silicone but had significantly better fidelity for loss of resistance, dural puncture and ultrasound imaging than the Simulab phantom. CONCLUSION: Low-cost neuraxial phantoms with fidelity comparable to commercial models can be produced using CT data and low-cost infrastructure consisting of FLOS software and desktop 3D printers.

Summative Objective Structured Clinical Examination Assessment at the End of Anesthesia Residency for Perioperative Ultrasound.

While standardized examinations and data from simulators and phantom models can assess knowledge and manual skills for ultrasound, an Objective Structured Clinical Examination (OSCE) could assess workflow understanding. We recruited 8 experts to develop an OSCE to assess workflow understanding in perioperative ultrasound. The experts used a binary grading system to score 19 graduating anesthesia residents at 6 stations. Overall average performance was 86.2%, and 3 stations had an acceptable internal reliability (Kuder-Richardson formula 20 coefficient >0.5). After refinement, this OSCE can be combined with standardized examinations and data from simulators and phantom models to assess proficiency in ultrasound.

Changes in Tricuspid Annular Geometry in Patients with Functional Tricuspid Regurgitation.

OBJECTIVE: To determine whether the indices of tricuspid annular dynamics that signify irreversible tricuspid valvular remodeling can improve surgical decision making by helping to better identify patients with functional tricuspid regurgitation who could benefit from annuloplasty. DESIGN: Retrospective analysis study. SETTING: Tertiary hospital. PARTICIPANTS: A total number of 55 patients were selected, 18 with functional tricuspid valve (TV) regurgitation and 37 normal nonregurgitant TVs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: When comparing the basal, mid, and longitudinal diameters of the right ventricle between the nonregurgitant valve (NTR) group and the functional tricuspid regurgitation (FTR) group, tricuspid annulus was more dilated (p < 0.001, p = 0.001, and p = 0.006, respectively) and less nonplanar (p < 0.001) in the FTR group. At end-systole (ES), the posterolateral-anteroseptal axis was significantly greater in the FTR group than in the NTR group (mean difference = 7.15 mm; p < 0.001). The right ventricle in the FTR group was also significantly dilated with greater leaflet restriction (p = 0.015). CONCLUSIONS: As compared to NTR TVs, FTR is associated with identifiable indices of tricuspid annular structural changes that are indicative of irreversible remodeling.

Dynamic Three-Dimensional Geometry of the Aortic Valve Apparatus-A Feasibility Study.

OBJECTIVE: To provide (1) an overview of the aortic valve (AV) apparatus anatomy and nomenclature, and (2) data regarding the normal AV apparatus geometry and dynamism during the cardiac cycle obtained from three-dimensional transesophageal echocardiography (3D TEE). DESIGN: Retrospective feasibility study. SETTING: A single-center university teaching hospital. PARTICIPANTS: The study was performed on data of 10 patients with a nonregurgitant, nonstenotic aortic valve undergoing cardiac surgery. INTERVENTIONS: Intraoperative 3D TEE was performed on all the participants using the Siemens ACUSON SC2000 ultrasound system and Z6Ms transducer (Siemens Medical Systems, Mountainview, CA). MEASUREMENTS AND MAIN RESULTS: Dynamic offline analyses were performed with Siemens eSie valve analytical software in a semiautomated fashion. Forty-five parameters were exported of which 13 were selected and analyzed. The cardiac cycle was divided into 4 quartiles to account for frame-rate variations. The annulus, sinus of Valsalva (SoV) and sinotubular junction (STJ) areas, diameter, perimeter and height, aortic leaflet height, leaflet coaptation height, and aortic valve-mitral valve angle changed significantly during the cardiac cycle (p < 0.001). STJ expanded more than both the annulus and the SoV (p < 0.001). The maximum aortic valve leaflet height change was greater in the left and right versus noncoronary leaflet (p < 0.001). CONCLUSIONS: The semiautomated AV apparatus dynamic assessment using eSie valve software is a clinically feasible technique and can be performed readily in the operating room. It has the potential to significantly impact intraoperative decision-making in cases suitable for AV repair. The AV apparatus is a dynamic structure and demonstrates significant changes during the cardiac cycle.

Mitochondrial Dysfunction in Atrial Tissue of Patients Developing Postoperative Atrial Fibrillation.

BACKGROUND: Mitochondria are the major site of cellular oxidation. Metabolism and oxidative stress have been implicated as possible mechanisms for postoperative atrial fibrillation (POAF) after cardiac operations. Establishing the precise nature of mitochondrial dysfunction as an etiologic factor for oxidative stress-related cell death and apoptosis could further the understanding of POAF. To establish this relationship, mitochondrial function was studied in patients undergoing cardiac operations that developed POAF and compared it with patients without POAF. METHODS: Right atrial tissue and serum samples were collected from 85 patients before and after cardiopulmonary bypass. Microarray analysis (36 patients) and RNA sequencing (5 patients) were performed on serum and atrial tissues, respectively, for identifying significantly altered genes in patients who developed POAF. On the basis of these results, Western blot was performed in 52 patients for the genes that were most altered, and functional pathways were established. RESULTS: POAF developed in 30.6% (n = 26) of patients. Serum microarray showed significant fold changes in the expression of 49 genes involved in inflammatory response, oxidative stress, apoptosis, and amyloidosis (p < 0.05) in the POAF group. Similarly, RNA sequencing demonstrated an increased expression of genes associated with inflammatory response, fatty acid metabolism, and apoptosis in the POAF group (false discovery rate > 0.05). Immunoblotting showed a significant increase in TNFAIP6 (tumor necrosis factor, α-induced protein 6; p = 0.02) and transforming growth factor-ß (p = 0.04) after cardiopulmonary bypass in the POAF group. There was a significant decrease in PGC-1α (peroxisome proliferator-activated receptor-γ coactivator-1α; p = 0.002) and CPT1 (carnitine palmitoyltransferase I; p < 0.0005) in the POAF group after cardiopulmonary bypass. CONCLUSIONS: Compared with patients without POAF, those with POAF demonstrated mitochondrial dysfunction at various levels that are suitable for potential pharmacotherapy.

Percutaneous Valve in Valve Implantation for Dysfunctional Bioprosthetic Valves: A Case Report.

Percutaneous valve-in-valve therapy is a life-saving procedure for patients at high risk of reoperation due to dysfunctional bioprosthetic valves. We have reviewed 3 typical cases of a valve-in-valve procedure using high-quality images to demonstrate the suitability of this method for aortic, mitral, and tricuspid positions. Three-dimensional transesophageal echocardiography combined with other modalities such as computerized tomography and fluoroscopy are key elements for anesthesia and procedural guidance, especially as immediate tools to assess valvular function and specific procedure-related complications.

Artificial intelligence in mitral valve analysis.

BACKGROUND: Echocardiographic analysis of mitral valve (MV) has become essential for diagnosis and management of patients with MV disease. Currently, the various software used for MV analysis require manual input and are prone to interobserver variability in the measurements. AIM: The aim of this study is to determine the interobserver variability in an automated software that uses artificial intelligence for MV analysis. SETTINGS AND DESIGN: Retrospective analysis of intraoperative three-dimensional transesophageal echocardiography data acquired from four patients with normal MV undergoing coronary artery bypass graft surgery in a tertiary hospital. MATERIALS AND METHODS: Echocardiographic data were analyzed using the eSie Valve Software (Siemens Healthcare, Mountain View, CA, USA). Three examiners analyzed three end-systolic (ES) frames from each of the four patients. A total of 36 ES frames were analyzed and included in the study. STATISTICAL ANALYSIS: A multiple mixed-effects ANOVA model was constructed to determine if the examiner, the patient, and the loop had a significant effect on the average value of each parameter. A Bonferroni correction was used to correct for multiple comparisons, and P = 0.0083 was considered to be significant. RESULTS: Examiners did not have an effect on any of the six parameters tested. Patient and loop had an effect on the average parameter value for each of the six parameters as expected (P < 0.0083 for both). CONCLUSION: We were able to conclude that using automated analysis, it is possible to obtain results with good reproducibility, which only requires minimal user intervention.

Use of 3-Dimensional Printing to Create Patient-Specific Thoracic Spine Models as Task Trainers.

BACKGROUND AND OBJECTIVES: Thoracic epidural anesthesia is a technically challenging procedure with a high failure rate of 24% to 32% nationwide. Residents in anesthesiology have limited opportunities to practice this technique adequately, and there are no training tools available for this purpose. Our objective was to build a low-cost patient-specific thoracic epidural training model. METHODS: We obtained thoracic computed tomography scan data from patients with normal and kyphotic spine. The thoracic spine was segmented from the scan, and a 3-dimensional model of the spine was generated and printed. It was then placed in a customized wooden box and filled with different types of silicone to mimic human tissues. Attending physicians in our institution then tested the final model. They were asked to fill out a brief questionnaire after the identification of the landmarks and epidural space using ultrasound and real-time performance for a thoracic epidural on the model (Supplemental Digital Content 1, http://links.lww.com/AAP/A197). Likert scoring system was used for scoring. RESULTS: The time to develop this simulator model took less than 4 days, and the materials cost approximately $400. Fourteen physicians tested the model for determining the realistic sensation while palpating the spinous process, needle entry through the silicone, the "pop" sensation and ultrasound fidelity of the model. Whereas the tactile fidelity scores were "neutral" (3.08, 3.06, and 3.0, respectively), the ultrasound guidance and overall suitability for residents were highly rated as being the most realistic (4.85 and 4.0, respectively). CONCLUSIONS: It is possible to develop homemade, low-cost, patient-specific, and high-fidelity ultrasound guidance simulators for resident training in thoracic epidurals using 3-dimensional printing technology.

Neuropeptide Y3-36 incorporated into PVAX nanoparticle improves functional blood flow in a murine model of hind limb ischemia.

We generated a novel nanoparticle called PVAX, which has intrinsic antiapoptotic and anti-inflammatory properties. This nanoparticle was loaded with neuropeptide Y3-36 (NPY3-36), an angiogenic neurohormone that plays a central role in angiogenesis. Subsequently, we investigated whether PVAX-NPY3-36 could act as a therapeutic agent and induce angiogenesis and vascular remodeling in a murine model of hind limb ischemia. Adult C57BL/J6 mice (n = 40) were assigned to treatment groups: control, ischemia PBS, ischemia PVAX, ischemia NPY3-36, and Ischemia PVAX-NPY3-36 Ischemia was induced by ligation of the femoral artery in all groups except control and given relevant treatments (PBS, PVAX, NPY3-36, and PVAX-NPY3-36). Blood flow was quantified using laser Doppler imaging. On days 3 and 14 posttreatment, mice were euthanized to harvest gastrocnemius muscle for immunohistochemistry and immunoblotting. Blood flow was significantly improved in the PVAX-NPY3-36 group after 14 days. Western blot showed an increase in angiogenic factors VEGF-R2 and PDGF-ß (P = 0.0035 and P = 0.031, respectively) and antiapoptotic marker Bcl-2 in the PVAX-NPY3-36 group compared with ischemia PBS group (P = 0.023). Proapoptotic marker Smad5 was significantly decreased in the PVAX-NPY3-36 group as compared with the ischemia PBS group (P = 0.028). Furthermore, Y2 receptors were visualized in endothelial cells of newly formed arteries in the PVAX-NPY3-36 group. In conclusion, we were able to show that PVAX-NPY3-36 can induce angiogenesis and arteriogenesis as well as improve functional blood flow in a murine model of hind limb ischemia.NEW & NOTEWORTHY Our research project proposes a novel method for drug delivery. Our patented PVAX nanoparticle can detect areas of ischemia and oxidative stress. Although there have been studies about delivering angiogenic molecules to areas of ischemic injury, there are drawbacks of nonspecific delivery as well as short half-lives. Our study is unique because it can specifically deliver NPY3-36 to ischemic tissue and appears to extend the amount of time therapy is available, despite NPY3-36's short half-life.

Making three-dimensional echocardiography more tangible: a workflow for three-dimensional printing with echocardiographic data.

Three-dimensional (3D) printing is a rapidly evolving technology with several potential applications in the diagnosis and management of cardiac disease. Recently, 3D printing (i.e. rapid prototyping) derived from 3D transesophageal echocardiography (TEE) has become possible. Due to the multiple steps involved and the specific equipment required for each step, it might be difficult to start implementing echocardiography-derived 3D printing in a clinical setting. In this review, we provide an overview of this process, including its logistics and organization of tools and materials, 3D TEE image acquisition strategies, data export, format conversion, segmentation, and printing. Generation of patient-specific models of cardiac anatomy from echocardiographic data is a feasible, practical application of 3D printing technology.

Tricuspid annulus: A spatial and temporal analysis.

BACKGROUND: Traditional two-dimensional (2D) echocardiographic evaluation of tricuspid annulus (TA) dilation is based on single-frame measurements of the septolateral (S-L) dimension. This may not represent either the axis or the extent of dynamism through the entire cardiac cycle. In this study, we used real-time 3D transesophageal echocardiography (TEE) to analyze geometric changes in multiple axes of the TA throughout the cardiac cycle in patients without right ventricular abnormalities. MATERIALS AND METHODS: R-wave-gated 3D TEE images of the TA were acquired in 39 patients undergoing cardiovascular surgery. The patients with abnormal right ventricular/tricuspid structure or function were excluded from the study. For each patient, eight points along the TA were traced in the 3D dataset and used to reconstruct the TA at four stages of the cardiac cycle (end- and mid-systole, end- and mid-diastole). Statistical analyses were applied to determine whether TA area, perimeter, axes, and planarity changed significantly over each stage of the cardiac cycle. RESULTS: TA area (P = 0.012) and perimeter (P = 0.024) both changed significantly over the cardiac cycle. Of all the axes, only the posterolateral-anteroseptal demonstrated significant dynamism (P < 0.001). There was also a significant displacement in the vertical axis between the points and the regression plane in end-systole (P < 0.001), mid-diastole (P = 0.014), and mid-systole (P < 0.001). CONCLUSIONS: The TA demonstrates selective dynamism over the cardiac cycle, and its axis of maximal dynamism is different from the axis (S-L) that is routinely measured with 2D TEE.