Abstract 13724: Myocardial Tissue Sensitization With Heat-activated Liposomal Doxorubicin Will Result in Enhanced Lesion Progression After Radiofrequency Ablation

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Duy T Nguyen ◽  
Lijun Zheng ◽  
Joseph Schuller ◽  
William Sauer

Introduction: Chronic durable lesions after radiofrequency ablation (RFA) of myocardial tissue remain difficult to achieve. Tissue exposed to RFA will often recover electrical activity despite initial dormancy. Heat sensitive liposomes (HSL) carrying doxorubicin has been shown to enhance RF destruction of tumors. Hypothesis: We sought to evaluate whether HSL doxorubicin will improve myocardial RFA lesion durability. Methods: Using an in vivo porcine model, 3 linear RF ablations per animal were performed by blinded operators in the right atrium after systemic HSL doxorubicin infusion or saline control: posterior (20W), septal (30W), and lateral (40W). Each line was created under standardized 3D mapping settings with inter-lesion distances of 4-6 mm to intentionally simulate linear RF gaps. Voltage mapping was performed immediately after ablation (Day 0) and after 2 weeks of survival. Comparisons were made in linear low voltage areas (LVA) from Day 0 to 2 weeks. Pathological staining of porcine RA ablation was also performed to assess for histological linear gaps. Results: There was no immediate difference in Day 0 LVA < 0.5 mV after ablation for HSL and controls. However, a significant increase in LVA < 0.5 mV was observed at 2 weeks in HSL animals (figure) with lesion progression in 3/5, compared to 0/4 controls, p< 0.05. There were fewer gaps identified with voltage remapping and on histology for HSL subjects compared to controls. Conclusions: RFA with concurrent HSL doxorubicin will be more durable and result in lesion progression with fewer linear gaps over time. Further confirmatory studies are needed.

2017 ◽  
Vol 64 (3) ◽  
pp. 491-499 ◽  
Author(s):  
Ole Gemeinhardt ◽  
Franz G.M. Poch ◽  
Bernhard Hiebl ◽  
Urte Kunz-Zurbuchen ◽  
Giuliano M. Corte ◽  
...  

2021 ◽  
Vol 10 (9) ◽  
pp. 1862
Author(s):  
Leszek Gromadziński ◽  
Agnieszka Skowrońska ◽  
Piotr Holak ◽  
Michał Smoliński ◽  
Ewa Lepiarczyk ◽  
...  

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a severe disease affecting the human venous system, accompanied by high morbidity and mortality rates. The aim of the study was to establish a new porcine VTE model based on the formation of the thrombus in vivo. The study was performed on 10 castrated male pigs: thrombus was formed in each closed femoral vein and then successfully released from the right femoral vein into the circulation of animals. In six pigs PE was confirmed via both computed tomography pulmonary angiography and an autopsy. Our research presents a novel experimental porcine model of VTE that involves inducing DVT and PE in the same animal in vivo, making it suitable for advanced clinical research and testing of future therapies.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Nicolò Sisti ◽  
Amato Santoro ◽  
Claudia Baiocchi ◽  
Antonio Biancofiore ◽  
Simone Pistoresi ◽  
...  

Abstract A 38 years-old man was admitted to our hospital after ventricular tachycardia with left-bundle-branch block and inferior axis morphology. After undergoing different examinations the criteria for the diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) were met. An electrophysiological study was then performed together with endocardial bipolar and unipolar voltage map. Unipolar and bipolar voltage mapping of the right ventricle showed low voltage areas and corresponding fragmented potentials from the tricuspid annulus to the inferior apex. On the right ventricular outer tract (RVOT), the bipolar voltage mapping was normal while the unipolar mapping showed low-voltage areas in the antero-septal outer tract. An off-line map was used to perform speckle tracking analysis on intracardiac echocardiography (ICE) clips of right ventricle and standard echocardiography. A reduction of the strain analysis was stored in correspondence of the fragmented electrograms area, in particular, speckle tracking analysis on ICE views showed a reduction of the RV LS in the segments below tricuspid valve, in the three different myocardial layers. The endocardial longitudinal strain was reduced from sub-tricuspidalic segments to the RV apex in accordance with the fragmentated potentials stored during voltage mapping. On the contrary, at anterior RVOT wall, the unipolar voltage mapping showed fragmented potentials and the STE analysis revealed a reduced epicardial LS. This case report lays emphasis on the importance of the integration of ICE-derived right ventricular strain and voltage mapping in the improvement of the sensibility of an early diagnosis of the ARVC.


EP Europace ◽  
2020 ◽  
Author(s):  
Ahmed M Al-Kaisey ◽  
Ramanathan Parameswaran ◽  
Stephen A Joseph ◽  
Peter M Kistler ◽  
Joseph B Morton ◽  
...  

Abstract Aims Prior studies have described a variety of mechanisms for atrial fibrillation (AF) originating in the right atrium (RA). In this study, we report a series of patients in whom an extensive right atrial free wall low-voltage zone (LVZ) served as the AF substrate. Methods and results Five patients with a clinical syndrome of paroxysmal AF and atrial tachycardia (AT) underwent electrophysiologic evaluation. Five patients (3 M; age 52 ± 7 years) had symptomatic paroxysmal AF for (28 ± 17 months) not responsive to medical therapy. At the initial EP study, AT was inducible in four patients and was spontaneous in one patient. In all patients, tachycardia instability precluded detailed AT mapping. Sinus or pace maps indicated an extensive LVZ in the lateral RA trabeculated free wall which consisted of regions of low amplitude complex signals interspersed between electrically silent areas. Radiofrequency ablation aimed at rendering the LVZ electrical inert was successful in eliminating AF in four of five patients. At a follow-up of 28 ± 15 months, one patient had an isolated recurrence of AF. However, two patients required repeat ablation for recurrent AT. Conclusion An extensive LVZ in the trabeculated RA free wall constitutes an unusual substrate for AF. These patients also demonstrate unstable ATs originating from the same zone. Radiofrequency ablation to render the low-voltage zone electrically inert is an effective strategy to manage AF and AT.


1991 ◽  
Vol 30 (01) ◽  
pp. 35-39 ◽  
Author(s):  
H. S. Durak ◽  
M. Kitapgi ◽  
B. E. Caner ◽  
R. Senekowitsch ◽  
M. T. Ercan

Vitamin K4 was labelled with 99mTc with an efficiency higher than 97%. The compound was stable up to 24 h at room temperature, and its biodistribution in NMRI mice indicated its in vivo stability. Blood radioactivity levels were high over a wide range. 10% of the injected activity remained in blood after 24 h. Excretion was mostly via kidneys. Only the liver and kidneys concentrated appreciable amounts of radioactivity. Testis/soft tissue ratios were 1.4 and 1.57 at 6 and 24 h, respectively. Testis/blood ratios were lower than 1. In vitro studies with mouse blood indicated that 33.9 ±9.6% of the radioactivity was associated with RBCs; it was washed out almost completely with saline. Protein binding was 28.7 ±6.3% as determined by TCA precipitation. Blood clearance of 99mTc-l<4 in normal subjects showed a slow decrease of radioactivity, reaching a plateau after 16 h at 20% of the injected activity. In scintigraphic images in men the testes could be well visualized. The right/left testis ratio was 1.08 ±0.13. Testis/soft tissue and testis/blood activity ratios were highest at 3 h. These ratios were higher than those obtained with pertechnetate at 20 min post injection.99mTc-l<4 appears to be a promising radiopharmaceutical for the scintigraphic visualization of testes.


1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.


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