Potential anti-proliferative activity of Salix mucronata and Triticum spelta plant extracts on liver and colorectal cancer cell lines.

Cancer's etiology is linked to oxidative stress. As a result, it's vital to find effective natural antioxidant remedies. Salix mucronata and Triticum spelta plant extracts were prepared using five different solvents and examined for their cytotoxicity against liver HepG2 cancer cell line. It was found that Salix mucronata ethanolic extract is high in antioxidant mediated anti-cancer activity. The functional constituents (phenolic and flavonoids) as well as preparation of different ethanolic concentrations used to study their properties that include DPPH, oxygen, hydroxyl, nitrogen radical scavenging activities, ferric reducing power and metal chelating activities. The MTT assay was used to determine antioxidant-mediated anti-cancer activity against human liver (HepG2) and colorectal (Caco-2) cancer cells to calculate the half-maximal growth inhibitory concentration (IC50). Moreover, flow cytometry analysis was used to quantify the apoptotic effect on the treated cancer cells. Additionally, qRTPCR of p53, BCL2, Cyclin D, MMP9 and VEGF were measured. Furthermore, HPLC was used to assess the most effective ingredients of the plant extract. Salix mucronata 50% ethanol extract had the highest polyphenolic content, anti-oxidant, and anti-proliferative activity. Salix mucronata increased the number of total apoptotic cells, and caused an upregulation of p53 gene expression by more than five folds and a downregulation of gene expression level of BCL2, Cyclin D, MMP9 and VEGF by more than five folds. Consequently, that could modulate oxidative stress and improve the effectiveness of cancer therapy. Results, also, showed that Triticum spelta ethanolic extract was less effective than Salix mucronata. Therefore, Salix mucronata ethanolic extract represents promising surrogate natural therapy for apoptosis-mediated cancer and recommended for further investigation using animal model.

Impact of ICD artifact burden on late gadolinium enhancement cardiac MR imaging in patients undergoing ventricular tachycardia ablation.

BACKGROUND: Cardiac magnetic resonance imaging (CMRI) is the gold standard for myocardial scar evaluation. Although ideal for substrate assessment in ventricular tachycardia (VT), most patients have an implantable cardioverter-defibrillator (ICD) at presentation for ablation. This study evaluates the ICD artifact burden during standard late gadolinium enhancement CMRI (LGE-CMRI) evaluation of myocardial scar in VT patients with ICDs. METHODS: Thirty-one patients with ICD and cardiomyopathy underwent LGE-CMRI using 1.5-T magnetic resonance scanner before VT ablation. Using the American Heart Association (AHA) 17-segment model, short-axis LGE series were analyzed for artifact burden localization and assessment. RESULTS: Preablation CMRI was performed in 31 patients with single chamber (n = 13), dual chamber (n = 11), and biventricular (n = 7) ICDs. Pre- and post-MRI ICD parameters were unchanged. All patients had susceptibility artifact and 51.6% (256 of 496) of segments were affected by artifact. The artifact area (178 ± 136 cm(2) ) resulted in an artifact burden of 54 ± 21% of the LV myocardial area (327 ± 15 cm(2) ). The anterior wall was most affected by artifact (89%) compared with 52%, 49%, and 23% in the lateral, septal, and inferior walls, respectively (P < 0.0001). The apical segments had more artifact burden (66%) than the mid (49%) and basal (44%) segments (P = 0.0005). Artifact area correlated with ICD-heart distance on anteroposterior chest radiograph (r = 0.42, P = 0.021) and body mass index (r = -0.48, P = 0.008). CONCLUSIONS: Current clinical LGE-CMRI scar imaging protocols produce ICD artifacts that affect >50% of the LV myocardium and correlate with the ICD-heart distance. This significantly limits the application of CMRI for image-guided VT ablation.

Impact of fluoroscopy unit on the accuracy of a magnet-based electroanatomic mapping and navigation system: an in vitro and in vivo validation study.

INTRODUCTION: During mapping and ablation procedures, the movement of large ferromagnetic items (i.e., fluoroscopic equipment) introduce heterogeneities in the electromagnetic field, which may affect the accuracy of electromagnet-based navigation. We aimed to assess the impact of common periprocedural fluoroscopic equipment movement on the accuracy of an electromagnet-based navigation system. METHODS AND RESULTS: The impact of fluoroscopic equipment movement on the accuracy of the Carto® 3 System (Biosense Webster, Inc., Diamond Bar, CA, USA) was assessed both in vitro (n = 20 patients, phantom model) and in vivo (n = 18 patients). Location recordings were obtained with unchanged catheter position for fluoroscopic equipment rotational movements (RMs) and maximal to closest distance (MD to CD) to phantom/patient. The effects of both single- and biplane fluoroscopy were assessed. In vitro, the movement of fluoroscopic equipment resulted in an average catheter location estimation error of 0.8 mm (interquartile range 0.3-1.3). The maximal location estimation errors with MD to CD movement and RM were 2.3 mm and 1.3 mm, respectively. Changing from single-plane to biplane setup resulted in an average location estimation change of 1.5 mm (maximum 2.1). Larger location changes were observed in vivo (2.9 mm vs 0.8 mm, P < 0.0001) with 28.7% of these exceeded 4 mm versus none of the in vitro measurements (P < 0.0001). CONCLUSION: Although fluoroscopy manipulation affected the accuracy of the Carto® 3 System, the in vitro data suggest that these inaccuracies are likely of limited clinical consequences. The larger in vivo inaccuracies are most likely due to nonferromagnetic interferences, such as respiratory or cardiac movements.

Assessment of ventricular tachycardia scar substrate by intracardiac echocardiography.

BACKGROUND: Intracardiac echocardiography (ICE) is increasingly used to guide complex ablation procedures. This study aimed to assess the scar substrate of ventricular tachycardia (VT) by ICE in patients undergoing VT ablation. METHODS: In 22 patients undergoing VT ablation (10 ischemic, 12 nonischemic), the Biosense CARTOSOUND module (Biosense Webster, Diamond Bar, CA, USA) was used for three-dimensional reconstruction of the ventricles. The characteristics and appearance with ICE imaging of voltage-defined scar zones (bipolar voltage <0.5 mV), border zones (0.5-1.5 mV), and normal myocardium (>1.5 mV) on electroanatomic maps were evaluated. The standard image analysis software Image J (National Institutes of Health, Bethesda, MD, USA) was used to analyze signal intensity (mean pixel signal intensity unit [SIU]) and heterogeneity (standard deviation of signal intensity in analyzed area) on ICE images. RESULTS: A total of 83 myocardial areas were analyzed from two-dimensional ICE images (15 scars, 31 border zones, and 37 normal). Voltage-defined scar zones had increased signal intensities compared to border zones (149 SIU vs 104 SIU, P < 0.0001) and normal myocardium (88 SIU, P < 0.0001). Border zones were more likely to have heterogeneous densities compared to normal myocardium (standard deviation of signal intensity 20 SIU vs 12 SIU, P < 0.0001). In receiver-operator characteristic analyses, signal intensity ≥ 137 SIU differentiated scar from nonscar zones (area under curve 0.91, P < 0.0001). Software-based color enhancement of areas with signal intensity ≥ 137 SIU allowed identification of the VT substrate in all 15 patients with voltage-defined scar zones. CONCLUSIONS: ICE provides important information about the VT anatomical substrate and may have potential to identify areas of scarred myocardium.

Integration of 3-dimensional scar models from SPECT to guide ventricular tachycardia ablation.

UNLABELLED: The integration of myocardial scar models in 3-dimensional (3D) mapping systems may provide a novel way of helping to guide ventricular tachycardia (VT) ablations. This study assessed the value of (201)Tl SPECT perfusion imaging to define ventricular myocardial scar areas and to characterize electrophysiology voltage-derived myocardial substrate categories of scar, border zone (BZ), and normal myocardium regions. Scar and BZ regions have been implicated in the genesis of ventricular arrhythmias. METHODS: Ten patients scheduled for VT ablation underwent (201)Tl SPECT before the ablation procedure. 3D left ventricular (LV) scar models were created from the SPECT images. These scar models were registered with the LV voltage maps and analyzed with a 17-segment cardiac model. Scar location and scar burden were compared between the SPECT scar models and voltage maps. In addition, (201)Tl SPECT uptake was quantified using a 68-segment cardiac model and compared among voltage-defined scar, BZ, and normal segments. RESULTS: 3D models of LV myocardium and scar were successfully created from (201)Tl SPECT images and integrated in a clinical mapping system. The surface registration error with the electrophysiology voltage map was 4.4 ± 1.0 mm. The 3D scar location from SPECT matched in 72% of the segments with the voltage map findings. All successful ablation sites were located within the SPECT-defined scar or within 1 cm of its border, with 73% of the successful ablation sites within 1 cm of the scar border. Voltage measurements in SPECT-defined scar and normal areas were 1.2 ± 1.7 and 3.4 ± 2.8 mV, respectively (P < 0.001). The fractional SPECT scar burden area (18.8% ± 5.2%) agreed better with the abnormal (scar plus BZ) voltage area (20.8% ± 15.7%) than with the scar voltage area (5.8% ± 5.8%). Mean normalized (201)Tl uptake was 55% ± 21% in the voltage-defined scar, 63% ± 20% in BZ, and 79% ± 17% in normal myocardial segments (P < 0.05 for scar or BZ vs. normal). CONCLUSION: 3D SPECT surface models of LV scar were accurately integrated into a clinical mapping system and predicted endocardial voltage-defined scar. These preliminary data support the possible use of widely available (201)Tl SPECT to facilitate substrate-guided VT ablations.

MRI-Guided ventricular tachycardia ablation: integration of late gadolinium-enhanced 3D scar in patients with implantable cardioverter-defibrillators.

BACKGROUND: Substrate-guided ablation of ventricular tachycardia (VT) in patients with implanted cardioverter-defibrillators (ICDs) relies on voltage mapping to define the scar and border zone. An integrated 3D scar reconstruction from late gadolinium enhancement (LGE) MRI could facilitate VT ablations. METHODS AND RESULTS: Twenty-two patients with ICD underwent contrast-enhanced cardiac MRI with a specific absorption rate of <2.0 W/kg before VT ablation. Device interrogation demonstrated unchanged ICD parameters immediately before, after, or at 68±21 days follow-up (P>0.05). ICD imaging artifacts were most prominent in the anterior wall and allowed full and partial assessment of LGE in 9±4 and 12±3 of 17 segments, respectively. In 14 patients with LGE, a 3D scar model was reconstructed and successfully registered with the clinical mapping system (accuracy, 3.9±1.8 mm). Using receiver operating characteristic curves, bipolar and unipolar voltages of 1.49 and 4.46 mV correlated best with endocardial MRI scar. Scar visualization allowed the elimination of falsely low voltage recordings (suboptimal catheter contact) in 4.1±1.9% of <1.5-mV mapping points. Display of scar border zone allowed identification of excellent pace mapping sites, with only limited voltage mapping in 64% of patients. Viable endocardium of >2 mm resulted in >1.5-mV voltage recordings despite up to 63% transmural midmyocardial scar successfully ablated with MRI guidance. All successful ablation sites demonstrated LGE (transmurality, 68±26%) and were located within 10 mm of transition zones to 0% to 25% scar in 71%. CONCLUSIONS: Contrast-enhanced cardiac MRI can be safely performed in selected patients with ICDs and allows the integration of detailed 3D scar maps into clinical mapping systems, providing supplementary anatomic guidance to facilitate substrate-guided VT ablations.