671Assessment of irrigated-tip radiofrequency catheter ablation lesion characteristics using different irrigation fluids on ex-vivo bovine myocardium

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
B Candemir ◽  
E Baskovski ◽  
K Esenboga ◽  
H Yorgun ◽  
K Aytemir ◽  
...  
Keyword(s):  
Catheter Ablation ◽  
Normal Saline ◽  
Ex Vivo ◽  
Clinical Success ◽  
Ringer Lactate ◽  
Lesion Depth ◽  
Irrigation Solution ◽  
Bovine Myocardium

Abstract Introduction Certain arrythmias, particularly of ventricular origin, necessitate deep lesions in order to achieve clinical success. The introduction of irrigated-tip radiofrequency (RF) catheters has allowed creation of deeper lesions and has decreased char formation. Although normal saline has been used as a standard solution, recent observations have suggested less ionic solutions may increase lesion depth. In this in-vitro study we aimed to characterize lesions created by irrigated-tip RF catheters using standard normal saline(NS), half-normal saline (HNS), and HNS-%2.5Dextrose (HNS-DEX/2) combination solutions. METHODS Bovine myocardium was placed firstly in ringer-lactate bath. Using irrigated-tip RF catheter ablation lesions were created serially using 30, 40, 50, 60, 70Watts with NS, HNS and HNS-DEX/2 as irrigation solutions. Lesion depths, steam pops and impedance drops were measured. Subsequently the experiment was repeated in normal saline bath. RESULTS Both HNS-DEX/2 and HNS irrigation solutions increase lesion depths when compared to normal saline (Table 1, Figure 1). Steam pops were more common and earlier with HNS-DEX/2 and HNS. DISCUSSION AND CONCLUSION Our findings suggest that less ionic irrigation solutions lead to increased lesion depths using similar RF power. If confirmed in-vivo, HNS and, particularly, HNS-DEX/2 as irrigation solution may increase ablation success for intramural/deep myocardial arrhythmic foci. Additionally, studies to assess safety of this strategy are necessary as intuitively deeper lesions may lead to more complications. Table 1 Irrigation Solution/Bath solution 30W/30ml(Lesion depth mm)(Impedance drop) 40W/30ml(Lesion depth mm)(Impedance drop) 50W/30ml(Lesion depth mm)(Impedance drop) 60W/30ml(Lesion depth mm)(Impedance drop) 70W/30ml(Lesion depth mm)(Impedance drop) HNS+%2.5D / Ringer Lactate 470->61 4.583->63 5.074->62SP+(32s) 6.080->66SP+(27s) 7.577->65SP+(26s) HNS/ Ringer Lactate 3.590->65 4.580->63SP+(34s) 5.073->59SP+(33s) 5.580->56SP+(28s) 6.583->64SP+(22s) NS/ Ringer Lactate 3.077->60 472->59 4.576->61 5.081->56 674->55 SP+(30s) HNS+%2.5D/Normal saline 3.573->67 598->63 5.573->58SP+(28s) 697->76SP+(26s) 7.570->58SP (25s) HNS/Normal saline 3.563->58 4.066->52 4.567->52 5.575->52 788->60SP+(28s) NS/Normal saline 2.566->58 3.063->52 4.073->58 5.077->55 5.568->44 Lesions created by irrigated tip radiofrequency catheter with bovine myocardium Abstract Figure 1

scholarly journals The Opportunities and Use of Imaging to Measure Target Engagement

2019 ◽  
Vol 25 (2) ◽  
pp. 127-136
Author(s):  
Juliana Maynard ◽  
Philippa Hart
Keyword(s):  
Ex Vivo ◽  
Clinical Success ◽  
Receptor Occupancy ◽  
Accurate Information ◽  
Target Engagement ◽  
Drug Molecule ◽  
Drug Discovery And Development ◽  
Ex Vivo Imaging

Lack of efficacy and poor safety outcomes are deemed to be the greatest causes of clinical failure of novel therapeutics. The use of biomarkers that give accurate information on target engagement, providing confidence that pharmacological activity in the target organ is being achieved, is key in optimizing clinical success. Without a measurement of target engagement, it can be very difficult to discern the basis for any lack of efficacy of a drug molecule within the pharmaceutical industry. Target engagement can be measured in both an in vitro and in vivo setting, and in recent years imaging measurements have been used frequently in drug discovery and development to assess target engagement and receptor occupancy in both human and animal models. From this perspective, we assess and look at the advancements in both in vivo and ex vivo imaging to demonstrate the enormous potential that imaging has as an application to provide a greater understanding of target engagement with a correlative therapeutic impact.

scholarly journals Rapid ratiometric biomarker detection with topically applied SERS nanoparticles

TECHNOLOGY ◽  
2014 ◽  
Vol 02 (02) ◽  
pp. 118-132 ◽  
Author(s):  
Yu "Winston" Wang ◽  
Altaz Khan ◽  
Madhura Som ◽  
Danni Wang ◽  
Ye Chen ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Clinical Success ◽  
Simultaneous Detection ◽  
Integration Time ◽  
In Vivo Experiments ◽  
Surface Enhanced Raman ◽  
Detection Probe ◽  
Multiple Cell

Multiplexed surface-enhanced Raman scattering (SERS) nanoparticles (NPs) offer the potential for rapid molecular phenotyping of tissues, thereby enabling accurate disease detection as well as patient stratification to guide personalized therapies or to monitor treatment outcomes. The clinical success of molecular diagnostics based on SERS NPs would be facilitated by the ability to accurately identify tissue biomarkers under time-constrained staining and detection conditions with a portable device. In vitro, ex vivo and in vivo experiments were performed to optimize the technology and protocols for the rapid detection (0.1-s integration time) of multiple cell-surface biomarkers with a miniature fiber-optic spectral-detection probe following a brief (5 min) topical application of SERS NPs on tissues. Furthermore, we demonstrate that the simultaneous detection and ratiometric quantification of targeted and nontargeted NPs allows for an unambiguous assessment of molecular expression that is insensitive to nonspecific variations in NP concentrations.

scholarly journals Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa

Microbiology ◽  
2020 ◽  
Vol 166 (12) ◽  
pp. 1171-1180 ◽  
Author(s):  
Esther Sweeney ◽  
Akshay Sabnis ◽  
Andrew M. Edwards ◽  
Freya Harrison
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ex Vivo ◽  
Clinical Success ◽  
Biofilm Growth ◽  
Content Type ◽  
The Matrix ◽  
Model Versus ◽  
High Doses

In vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in medium that mimics cystic fibrosis (CF) sputum versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and drug development pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.

Optimization of Clot Formation Methodology for Assessment of Neurothrombectomy Devices in Large Animal Thrombectomy Models

2020 ◽  
Author(s):  
Cedric Jimenez ◽  
Igor Polyakov ◽  
Leigh Kleinert ◽  
André Nelson ◽  
Mark Smith
Keyword(s):  
Reliable Method ◽  
Ex Vivo ◽  
Clinical Success ◽  
Model Development ◽  
Large Animal ◽  
Soft Or ◽  
Mechanical Devices ◽  
Clot Disruption

Abstract Neurothrombectomy devices are commonly evaluated for potential clinical success in porcine models of neurothromboembolism. The majority of preclinical evaluations for these devices are performed in the vasculature of swine or dog utilizing clots created ex vivo. This investigation was conducted to develop a faster, more reliable method for creating clots ex vivo for model development. Neurothrombectomy devices are designed to perform recanalization of arterial occlusions that cause acute ischemic stroke [1]. Recanalization can be achieved via clot disruption, aspiration, or retrieval using one or more mechanical devices. In order to evaluate these devices in vivo, a fast and reliable method for creating and delivering clots to a desired artery, thereby simulating a target site for neurothrombectomy, is essential. Two types of clot analogs (soft or firm) were created using two different methods in order to compare both their mechanical properties and their ability to reliably occlude selected arteries. Utilizing both methods, pre-formed clots were qualitatively compared in vitro to evaluate elasticity, stiffness, and functionality of delivery through a catheter. These evaluations were performed prior to in vivo assessment of the effectiveness of the analogs occlusion of selected arterial vasculature.

scholarly journals Effect of host-mimicking medium and biofilm growth on the ability of colistin to kill Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Esther Sweeney ◽  
Akshay Sabnis ◽  
Andrew M. Edwards ◽  
Freya Harrison
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Ex Vivo ◽  
Clinical Success ◽  
Biofilm Growth ◽  
The Matrix ◽  
Model Versus ◽  
High Doses ◽  
Fluorescent Tag

AbstractIn vivo biofilms cause recalcitrant infections with extensive and unpredictable antibiotic tolerance. Here, we demonstrate increased tolerance of colistin by Pseudomonas aeruginosa when grown in cystic fibrosis-mimicking medium versus standard medium in in vitro biofilm assays, and drastically increased tolerance when grown in an ex vivo CF model versus the in vitro assay. We used colistin conjugated to the fluorescent dye BODIPY to assess the penetration of the antibiotic into ex vivo biofilms and showed that poor penetration partly explains the high doses of drug necessary to kill bacteria in these biofilms. The ability of antibiotics to penetrate the biofilm matrix is key to their clinical success, but hard to measure. Our results demonstrate both the importance of reduced entry into the matrix in in vivo-like biofilm, and the tractability of using a fluorescent tag and benchtop fluorimeter to assess antibiotic entry into biofilms. This method could be a relatively quick, cheap and useful addition to diagnostic and R&D pipelines, allowing the assessment of drug entry into biofilms, in in vivo-like conditions, prior to more detailed tests of biofilm killing.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Kinetics of Various 99mTc-Sn-Pyrophosphate Compounds in the Rat

1977 ◽  
Vol 16 (04) ◽  
pp. 157-162 ◽  
Author(s):  
C. Schümichen ◽  
B. Mackenbrock ◽  
G. Hoffmann
Keyword(s):  
Normal Saline ◽  
Half Life ◽  
Compound A ◽  
Short Half Life ◽  
Low Concentrations ◽  
The Stability ◽  
Kinetics Of ◽  
In Vitro Stability

SummaryThe bone-seeking 99mTc-Sn-pyrophosphate compound (compound A) was diluted both in vitro and in vivo and proved to be unstable both in vitro and in vivo. However, stability was much better in vivo than in vitro and thus the in vitro stability of compound A after dilution in various mediums could be followed up by a consecutive evaluation of the in vivo distribution in the rat. After dilution in neutral normal saline compound A is metastable and after a short half-life it is transformed into the other 99mTc-Sn-pyrophosphate compound A is metastable and after a short half-life in bone but in the kidneys. After dilution in normal saline of low pH and in buffering solutions the stability of compound A is increased. In human plasma compound A is relatively stable but not in plasma water. When compound B is formed in a buffering solution, uptake in the kidneys and excretion in urine is lowered and blood concentration increased.It is assumed that the association of protons to compound A will increase its stability at low concentrations while that to compound B will lead to a strong protein bond in plasma. It is concluded that compound A will not be stable in vivo because of a lack of stability in the extravascular space, and that the protein bond in plasma will be a measure of its in vivo stability.

Significance of Platelet β-Adrenoceptors for Platelet Responses In Vivo and In Vitro

1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl
Keyword(s):  
Ex Vivo ◽  
High Dose ◽  
Platelet Aggregability ◽  
Adrenoceptor Agonist ◽  
Dose Infusion ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.

In Vivo Effect of Suloctidil as an Antiplatelet Agent

1979 ◽  
Vol 41 (03) ◽  
pp. 465-474 ◽  
Author(s):  
Marcia R Stelzer ◽  
Thomas S Burns ◽  
Robert N Saunders
Keyword(s):  
Ex Vivo ◽  
Antiplatelet Agent ◽  
Ratio Method ◽  
Platelet Aggregate ◽  
Permanent Effect ◽  
Platelet Aggregates ◽  
5 Ht Uptake ◽  
High Doses

SummaryThe relationship between the effects of suloctidil in vivo as an antiplatelet agent and in vitro as a modifier of platelet serotonin (5-HT) parameters was investigated. Suloctidil was found to be effective in reducing platelet aggregates formation in the retired breeder rat as determined using the platelet aggregate ratio method (PAR) with an ED50 of 16.1 mg/kg 24 hours post administration. In contrast to the hypothesis that 5-HT depletion is involved in the anti-aggregatory mechanism of suloctidil, no correlation was found between platelet 5- HT content and this antiplatelet activity. Reduction of platelet 5-HT content required multiple injections of high doses (100 mg/kg/day) of suloctidil. Suloctidil administration for 8 days at 100 mg/kg/day, which lowered platelet 5-HT content by 50%, resulted in no permanent effect on ex vivo platelet 5-HT uptake or thrombin-induced release, nor alteration in the plasma 5-HT level. However, these platelets exhibited a short-lived, significant increase in percent leakage of 5-HT after 30 minutes of incubation. Therefore, suloctidil treatment at high doses may with time result in platelet 5-HT depletion, however this effect is probably not related to the primary anti-aggregatory activity of the drug.

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