1. Introduction 
Implantable cardioverter-defibrillators (ICD) prevent sudden cardiac death (SCD) in patients after survived SCD or at risk of SCD due to impaired left ventricular function. However, the danger of inappropriate therapies is high, particularly in single-chamber devices. These superfluous electrical discharges can be harmful and impair patient quality of life. Atrial detection may improve device performance and reduce the risk of inappropriate shock.1,2 However atrial detection requires an atrial electrode which in itself carries a significant associated risk.3 One manufacturer, BIOTRONIK, developed a ventricular single chamber electrode with atrial sensing capabilities. The first electrode was the Kainox A+, which revealed excellent sensing capabilities.4 However, it was not commonly used due to electrode stiffness and large diameter (3.5 mm, 10.5 F). Further developments of this electrode lead to the creation of the Linoxsmart S DX lead, which has a smaller diameter (2.6 mm, 7.8 F) and demonstrates excellent implantation features and sensing capabilities.5 This paper depicts the placement of this electrode, in order to highlight the data from the master study and to demonstrate both the ease of implantation and the excellent sensing capabilities of this electrode. 
2. Case Presentation
<ol>
 <li> The patient was a 40 year-old female smoker with a history of coronary artery disease (CAD), recurrent anterior myocardial infarction (AMI) status-post percutaneous coronary intervention (PCI), impaired left ventricular function (LVEF= 25%), hypercholesterolemia and paroxysmal atrial fibrillation (PAF). </li>
 <li> Four months ago, medical therapy for heart failure was initiated. Her regimen included beta-blockers, ACE-inhibitors and diuretics; however, there was no improvement in left ventricular function.</li>
 <li> Due to her significantly impaired left ventricular function, the patient was at considerable risk of sudden cardiac death (SCD). </li>
 <li> On presentation, the patient was in sinus rhythm with loss of R-waves in the chest leads. A 24-hour holter monitor revealed a 32-minute episode of atrial fibrillation. </li>
 <li> The decision was made to implant a single-chamber ICD with atrial detection capability in order to monitor further episodes of atrial fibrillation and to avoid inappropriate therapy in an otherwise very active patient. </li>
</ol>
3. Diagnosis, Assessment, and Plan
<ol>
 <li> The treatment plan was to implant a Lumax VR-T DX defibrillator with a BIOTRONIK Linoxsmart S DX lead under regional anesthesia in the electrophysiological laboratory. </li>
 <li> A transthoracic echo was performed prior to implantation in order to re-evaluate left ventricular ejection fraction and to exclude a ventricular thrombus, which might prohibit defibrillator testing during implantation. </li>
</ol>
4. Implantation Procedure
<ol>
 <li> Peri-procedural preparation included a single intravenous dose of prophylactic antibiotic and subcutaneous heparin. Antithrombotic therapy was maintained because the risk of a coronary event outweighed the risk of bleeding during the procedure</li>
 <li> The patient was appropriately prepared and draped in a sterile manner. </li>
 <li> The patient was placed under moderate sedation, with appropriate monitoring including continuous electrical cardiac monitoring, continuous pulse oximetry, and non-invasive blood pressure monitoring.</li>
 <li> Sedation administered consisted of IV midazolam, fentanyl and propofol along with judicious application of topical anesthesia. </li>
 <li> The implantation began with puncture of the left subclavian vein through the intact skin and placement of a wire in the inferior vena cava (IVC) . The position was confirmed by X-ray. This unusual approach was used since most interventional electrophysiologists are more experienced in this transcutaneous approach, rather than the more lateral approach of puncturing the vein from the pocket. </li>
 <li> The skin was cut with a scalpel about 2cm below and parallel to the clavicles. After the pocket for the device was prepared below the left clavicle, the wire in the vein was drawn to the pocket and an 8 French sheath introduced with the Seldinger technique. </li>
 <li> The electrode was then introduced into the SVC via the sheath to the right atrium. After a curved stylet (S 65-K, Biotronik) was introduced into the electrode, the electrode was pushed though the tricuspid valve to the right ventricular outflow tract. </li>
 <li> A straight stylet (S 65-C, Biotronik) was then introduced into the electrode. The electrode fell to the inferior right ventricle and was maneuvered to the right ventricular apex. The position of the electrode tip as well as general position of the two electrodes in the atrium was monitored by X-ray. The two atrial ring electrodes were placed at the junction of the SVC and right atrium. </li>
 <li> After the electrode was appropriately positioned, measurements of the atrial and ventricular signals were performed.</li>
 <li> The pacing threshold for the ventricular electrode was measured (Time in Video = "7:27"). The atrial signal was measured between 6.5 and 8mv (Time in Video = "7:56"). The atrial signal was enhanced three times with the filter setting in the device. The ventricular signal was measured between 8.4 and 9.5 mV. With these sensing and pacing-thresholds, the electrode was fixed at the entrance of the subclavian vein. </li>
 <li> The electrode was then connected to the defibrillator. </li>
 <li> All measures were rechecked and ventricular fibrillation was induced by T-wave shock via the defibrillator and automatically terminated by the device. (Time in Video = "11:01") </li>
 <li> The patient was brought to the ward and remained in the hospital until the following day. On post-operative day 1, an X-ray was taken to confirm the position of the lead and to exclude a pneumothorax. Sensing and pacing thresholds were rechecked and were similar to intraoperative measurements. The patient was observed for approximately 4 hours in recovery and was also monitored after implantation. Overall, the implantation was successful and the patient was discharged from the hospital the following day. The first three-months of follow-up were eventless and sensing signals remained stable over this timeframe. </li>
</ol>

<ol>
	<li>B&#228;nsch, D., Steffgen, F., Gronefeld, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+1+1+trial+-+A+prospective+trial+of+a+dual-+versus+a+single-chamber+implantable+defibrillator+in+patients+with+slow+ventricular+tachycardias.">The 1+1 trial - A prospective trial of a dual- versus a single-chamber implantable defibrillator in patients with slow ventricular tachycardias.</a> Circulation. 110, 1022-1029 (2004).</li><li>Gilliam, F. R., Hayes, D. L., Boehmer, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Real+World+Evaluation+of+Dual-Zone+ICD+and+CRT-D+Programming+Compared+to+Single-Zone+Programming.">Real World Evaluation of Dual-Zone ICD and CRT-D Programming Compared to Single-Zone Programming.</a> The ALTITUDE REDUCES Study. Journal of Cardiovascular Electrophysiology. 22, 1023-1029 (2011).</li><li>Dewland, T. A., Pellegrini, C. N., Wang, Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-Chamber+Implantable+Cardioverter-Defibrillator+Selection+Is+Associated+With+Increased+Complication+Rates+and+Mortality+Among+Patients+Enrolled+in+the+NCDR+Implantable+Cardioverter-Defibrillator+Registry.">Dual-Chamber Implantable Cardioverter-Defibrillator Selection Is Associated With Increased Complication Rates and Mortality Among Patients Enrolled in the NCDR Implantable Cardioverter-Defibrillator Registry.</a> Journal of the American College of Cardiology. 58, 1007-1013 (2011).</li><li>Sticherling, C., Zabel, M., Spencker, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+a+Novel,+Single-Lead+Atrial+Sensing+System+With+a+Dual-Chamber+Implantable+Cardioverter-Defibrillator+System+in+Patients+Without+Antibradycardia+Pacing+Indications+Results+of+a+Randomized+Study.">Comparison of a Novel, Single-Lead Atrial Sensing System With a Dual-Chamber Implantable Cardioverter-Defibrillator System in Patients Without Antibradycardia Pacing Indications Results of a Randomized Study.</a> Circulation-Arrhythmia and Electrophysiology. 4, 56-63 (2011).</li><li>Safak, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+atrial+sensing+quality+in+ICD+patients+with+a+floating+atrial+dipole+ICD+lead+(interim+results).">Assessment of atrial sensing quality in ICD patients with a floating atrial dipole ICD lead (interim results).</a> Europace. , 1027-1027 (2011).</li><li>Deisenhofer, I., Kolb, C., Ndrepepa, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+current+dual+chamber+cardioverter+defibrillators+have+advantages+over+conventional+single+chamber+cardioverter+defibrillators+in+reducing+inappropriate+therapies?+A+randomized,+prospective+study.">Do current dual chamber cardioverter defibrillators have advantages over conventional single chamber cardioverter defibrillators in reducing inappropriate therapies? A randomized, prospective study.</a> J. Cardiovasc. Electrophysiol. 12, 134-142 (2001).</li><li>Dewland, T. A., Pellegrini, C. N., Wang, Y. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dual-Chamber+Implantable+Cardioverter-Defibrillator+Selection+Is+Associated+With+Increased+Complication+Rates+and+Mortality+Among+Patients+Enrolled+in+the+NCDR+Implantable+Cardioverter-Defibrillator+Registry.">Dual-Chamber Implantable Cardioverter-Defibrillator Selection Is Associated With Increased Complication Rates and Mortality Among Patients Enrolled in the NCDR Implantable Cardioverter-Defibrillator Registry.</a> Journal of the American College of Cardiology. 58, 1007-1013 (2011).</li><li>Poole, J. E., Gleva, M. J., Mela, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Complication+Rates+Associated+With+Pacemaker+or+Implantable+Cardioverter-Defibrillator+Generator+Replacements+and+Upgrade+Procedures+Results+From+the+REPLACE+Registry.">Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures Results From the REPLACE Registry.</a> Circulation. 122, 1553-1U43 (2010).</li><li>Niehaus, M., Schuchert, A., Thamasett, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multicenter+experiences+with+a+single+lead+electrode+for+dual+chamber+ICD+systems.">Multicenter experiences with a single lead electrode for dual chamber ICD systems.</a> Pacing Clin. Electrophysiol. 24, 1489-1493 (2001).</li><li>Gradaus, R., Block, M., Dorszewski, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Implantation+of+a+dual+chamber+pacing+and+sensing+single+pass+defibrillation+lead.">Implantation of a dual chamber pacing and sensing single pass defibrillation lead.</a> Pacing Clin. Electrophysiol. 24, 416-423 (2001).</li></ol>

Production and Free Access of this video-article is sponsored by BIOTRONIK.

Implantation of the new LinoxSMART S DX electrode along with the Lumax DX ICD, Biotronik, was as easy as the placement of any single chamber ICD. This experience is supported by data from the unpublished master DX-trial. 5 The LinoxSMART S DX electrode offers the advantage of atrial sensing without the disadvantage of an atrial lead. 	The atrial signal was stable over time in our patient as has been demonstrated in the DX-trial. 5
	Dual-chamber devices have demonstrated superiority over single-chamber detection in only one prospective randomized trial, called the 1+1 trial.1 In this trial, patients with slow VT were implanted with a dual-chamber ICD that was either programmed to dual- or single- chamber detection. The combined endpoint was the number of inappropriate therapies in response to SVTs and VTs below the detection rate. For this endpoint, the 1+1-trial demonstrated the significant superiority of dual-chamber (DCH) detection with a long tachycardia detection interval (TDI) compared with conventionally programmed single-chamber (SCH) detection. This finding was revisited by Deisenhofer et al., who randomly assigned patients to DCH- or SCH ICD implantation. However, their trial did not particularly address patients with slow VTs as the mean tachycardia detection interval was 368 ms, and concluded that single- and dual-chamber devices are equally effective for therapy in life-threatening ventricular tachyarrhythmias. DCH devices were shown have superior rhythm classification but were no different than SCH devices in terms of minimizing inappropriate therapies during SVTs. 6 Despite the advantages of a dual chamber ICD for diagnosis and differentiation of tachycardias, the concept of implanting it merely for the sake of detection is generally not accepted, because the improved detection is counter-balanced by the increased risk of lead complications, as well as increased mortality and morbidity.2,7,8 Therefore, improvement of implantation technique or a VDD-system for dual chamber detection is necessary.9,10. The LinoxSMART S DX electrode combined with the Lumax DX ICD offers this advantage. The sensing facilities are similar to a dual chamber devices and the complication rate is as low as in conventional single chamber ICDs. 5
Conclusion
The Lumax VR-T DX has been proven to reliably sense atrial signals and gather valuable information to allow for early detection of atrial arrhythmias. Furthermore, the device offers AV discrimination with SMART for safe shock reduction. The available atrial IEGM channel diagnoses the appropriateness of ICD detection and therapy, thereby reducing inappropriate shocks and gaining information to optimize device programming.

a new single chamber implantable defibrillator with atrial sensing: a practical demonstration of sensing and  ease of implantation

Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy and can protect patients from sudden cardiac death (SCD). However, inappropriate shocks may occur if tachycardias are misdiagnosed. Inappropriate shocks are harmful and impair patient quality of life. The risk of inappropriate therapy increases with lower detection rates programmed in the ICD. Single-chamber detection poses greater risks for misdiagnosis when compared with dual-chamber devices that have the benefit of additional atrial information. However, using a dual-chamber device merely for the sake of detection is generally not accepted, since the risks associated with the second electrode may outweigh the benefits of detection. Therefore, BIOTRONIK developed a ventricular lead called the LinoxSMART S DX, which allows for the detection of atrial signals from two electrodes positioned at the atrial part of the ventricular electrode. This device contains two ring electrodes; one that contacts the atrial wall at the junction of the superior vena cava (SVC) and one positioned at the free floating part of the electrode in the atrium. The excellent signal quality can only be achieved by a special filter setting in the ICD (Lumax 540 and 740 VR-T DX, BIOTRONIK). Here, the ease of implantation of the system will be demonstrated.

Watch this Scientific Journal Video about A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation at JoVE.com

A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation

Dual-chamber implantable cardioverter-defibrillators (ICDs) may improve detection of atrial fibrillation as well as differentiation of tachycardias. However, this advantage is undermined by complications associated with the second electrode, which is required in conventional dual chamber devices. Therefore, BIOTRONIK has developed a new electrode called the LinoxSMART S DX that, when used in conjunction with the Lumax DX ICD, offers dual-chamber detection without the risks associated with the second electrode.

Implantable cardioverter-defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy and can protect ...

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25.9K Views.  University Hospital of Rostock, Germany. Dual-chamber implantable cardioverter-defibrillators (ICDs) may improve detection of atrial fibrillation as well as differentiation of tachycardias. However, this advantage is undermined by complications associated with the second electrode, which is required in conventional dual chamber devices. Therefore, BIOTRONIK has developed a new electrode called the LinoxSMART S DX that, when used in conjunction with the Lumax DX ICD, offers dual-chamber detection with...

Video: A New Single Chamber Implantable Defibrillator with Atrial Sensing: A Practical Demonstration of Sensing and  Ease of Implantation

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

Rapid Point-of-Care Assay of Enoxaparin Anticoagulant Efficacy in Whole Blood

There is the need for a clinical assay to determine the extent to which a patient's blood is effectively anticoagulated by the low-molecular-weight-heparin (LMWH), enoxaparin. There are also urgent clinical situations where it would be important if this could be determined rapidly. The present assay is designed to accomplish this. We only assayed human blood samples that were spiked with known concentrations of enoxaparin. The essential feature of the present assay is the quantification of the efficacy of enoxaparin in a patient's blood sample by degrading it to complete inactivity with heparinase. Two blood samples were drawn into Vacutainer tubes (Becton-Dickenson; Franklin Lakes, NJ) that were spiked with enoxaparin; one sample was digested with heparinase for 5 min at 37 &deg;C, the other sample represented the patient's baseline anticoagulated status. The percent shortening of clotting time in the heparinase-treated sample, as compared to the baseline state, yielded the anticoagulant contribution of enoxaparin. We used the portable, battery operated Hemochron 801 apparatus for measurements of clotting times (International Technidyne Corp., Edison, NJ). The apparatus has 2 thermostatically controlled (37 &deg;C) assay tube wells. We conducted the assays in two types of assay cartridges that are available from the manufacturer of the instrument. One cartridge was modified to increase its sensitivity. We removed the kaolin from the FTK-ACT cartridge by extensive rinsing with distilled water, leaving only the glass surface of the tube, and perhaps the detection magnet, as activators. We called this our minimally activated assay (MAA). The use of a minimally activated assay has been studied by us and others. 2-4 The second cartridge that was studied was an activated partial thromboplastin time (aPTT) assay (A104). This was used as supplied from the manufacturer. The thermostated wells of the instrument were used for both the heparinase digestion and coagulation assays. The assay can be completed within 10 min. The MAA assay showed robust changes in clotting time after heparinase digestion of enoxaparin over a typical clinical concentration range. At 0.2 anti-Xa I.U. of enoxaparin per ml of blood sample, heparinase digestion caused an average decrease of 9.8% (20.4 sec) in clotting time; at 1.0 I.U. per ml of enoxaparin there was a 41.4% decrease (148.8 sec). This report only presents the experimental application of the assay; its value in a clinical setting must still be established.

Demonstration of a rapid quantitative assay of the inhibition of blood coagulation by the low-molecular-weight-heparin, enoxaparin. The contribution of enoxaparin is assessed by removing its influence through digestion with heparinase. A fuller description of the assay is detailed in our published paper.1 The assay still requires clinical confirmation.

There is the need for a clinical assay to determine the extent to which a patient's blood is effectively anticoagulated by the ...

Surgical Technique for Spinal Cord Delivery of Therapies: Demonstration of Procedure in Gottingen Minipigs

This is a compact visual description of a combination of surgical technique and device for the delivery of (gene and cell) therapies into the spinal cord. While the technique is demonstrated in the animal, the procedure is FDA-approved and currently being used for stem cell transplantation into the spinal cords of patients with ALS. While the FDA has recognized proof-of-principle data on therapeutic efficacy in highly characterized rodent models, the use of large animals is considered critical for validating the combination of a surgical procedure, a device, and the safety of a final therapy for human use. The size, anatomy, and general vulnerability of the spine and spinal cord of the swine are recognized to better model the human. Moreover, the surgical process of exposing and manipulating the spinal cord as well as closing the wound in the pig is virtually indistinguishable from the human. We believe that the healthy pig model represents a critical first step in the study of procedural safety.

Short visual description of the surgical technique and device used for the delivery of (gene and cell) therapies into the spinal cord. The technique is demonstrated in the animal but is entirely translatable and currently being used for human application.

This is a  compact visual description of a combination of surgical technique and device  for the  delivery of (gene and cell) therapies into the spinal ...

A New Murine Model of Endovascular Aortic Aneurysm Repair

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of Abdominal aortic aneurysm (AAA) pathophysiology. There is no abdominal aortic aneurysm endograft exclusion model cheap and reproducible, which would allow deep investigations of AAA before and after treatment. We hereby describe how to induce, and then to exclude with a covered coronary stentgraft an abdominal aortic aneurysm in a rat. The well known elastase induced AAA model was first reported in 19901 in a rat, then described in mice2. Elastin degradation leads to dilation of the aorta with inflammatory infiltration of the abdominal wall and intra luminal thrombus, matching with human AAA. Endovascular exclusion with small covered stentgraft is then performed, excluding any interactions between circulating blood and the aneurysm thrombus. Appropriate exclusion and stentgraft patency is confirmed before euthanasia by an angiography thought the left carotid artery. Partial control of elastase diffusion makes aneurysm shape different for each animal. It is difficult to create an aneurysm, which will allow an appropriate length of aorta below the aneurysm for an easy stentgraft introduction, and with adequate proximal and distal neck to prevent endoleaks. Lots of failure can result to stentgraft introduction which sometimes lead to aorta tear with pain and troubles to stitch it, and endothelial damage with post op aorta thrombosis. Giving aspirin to rats before stentgraft implantation decreases failure rate without major hemorrhage. Clamping time activates neutrophils, endothelium and platelets, and may interfere with biological analysis.

Histological and biochemical modifications after aneurysm endograft exclusion are still unclear. We describe a new model of endograft implantation on a murine aneurysm. Through thrombus analysis with and without persistant circulating blood stream interface, and new endovascular biomaterials evaluation, this model will help to better understand endovascular aneurysm exclusion pathobiology.

Endovascular aneurysm exclusion is a validated technique to prevent aneurysm rupture. Long-term results highlight technique limitations and new aspects of ...

Construction of Vapor Chambers Used to Expose Mice to Alcohol During the Equivalent of all Three Trimesters of Human Development

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal Alcohol Spectrum Disorders (FASDs). At the most severe end of the spectrum is Fetal Alcohol Syndrome (FAS), characterized by growth retardation, craniofacial dysmorphology, and neurobehavioral deficits. Studies with animal models, including rodents, have elucidated many molecular and cellular mechanisms involved in the pathophysiology of FASDs. Ethanol administration to pregnant rodents has been used to model human exposure during the first and second trimesters of pregnancy. Third trimester ethanol consumption in humans has been modeled using neonatal rodents. However, few rodent studies have characterized the effect of ethanol exposure during the equivalent to all three trimesters of human pregnancy, a pattern of exposure that is common in pregnant women. Here, we show how to build vapor chambers from readily obtainable materials that can each accommodate up to six standard mouse cages. We describe a vapor chamber paradigm that can be used to model exposure to ethanol, with minimal handling, during all three trimesters. Our studies demonstrate that pregnant dams developed significant metabolic tolerance to ethanol. However, neonatal mice did not develop metabolic tolerance and the number of fetuses, fetus weight, placenta weight, number of pups/litter, number of dead pups/litter, and pup weight were not significantly affected by ethanol exposure. An important advantage of this paradigm is its applicability to studies with genetically-modified mice. Additionally, this paradigm minimizes handling of animals, a major confound in fetal alcohol research.

We demonstrate the construction of alcohol vapor chambers using readily available materials that simultaneously house 6 mouse cages. We further describe their use in a mouse model of fetal alcohol exposure equivalent to all 3&#160;trimesters of human pregnancy. This paradigm exposes animals during gestation and postnatal days 1-12.

Exposure to alcohol during development can result in a constellation of morphological and behavioral abnormalities that are collectively known as Fetal ...

Murine Model of Femoral Artery Wire Injury with Implantation of a Perivascular Drug Delivery Patch

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. While these therapies lead to the rapid restoration of blood flow, these technologies remain limited by restenosis in the case of bare metal stents and angioplasty, or reduced healing and possibly enhanced risk of thrombosis in the case of drug eluting stents. A key pathophysiological mechanism in the formation of restenosis is intimal hyperplasia caused by the activation of vascular smooth muscle cells and inflammation due to arterial stretch and injury. Surgeries that induce arterial injury in genetically modified mice are useful for the mechanistic study of the vascular response to injury but are often technically challenging to perform in mouse models due to the their small size and lack of appropriate sized devices. We describe two approaches for a surgical technique that induces endothelial denudation and arterial stretch in the femoral artery of mice to produce robust neointimal hyperplasia. The first approach creates an arteriotomy in the muscular branch of the femoral artery to obtain vascular access. Following wire injury this arterial branch is ligated to close the arteriotomy. A second approach creates an arteriotomy in the main femoral artery that is later closed through localized cautery. This method allows for vascular access through a larger vessel and, consequently, provides a less technically demanding procedure that can be used in smaller mice. Following either method of arterial injury, a degradable drug delivery patch can be placed over or around the injured artery to deliver therapeutic agents.

We describe a surgical technique that produces wire injury in the femoral artery of mice to induce neointimal hyperplasia to serve as a model testing system for the perivascular delivery of therapeutic compounds for the inhibition of restenosis.

Percutaneous interventions including balloon angioplasty and stenting have been used to restore blood flow in vessels with occlusive vascular disease. ...

Demonstration of the Rat Ischemic Skin Wound Model

The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and unrelieved pressure due to immobility. Animal models have been developed that attempt to mimic these conditions for the purpose of furthering our understanding of the complexity of chronic wounds. The model described herein is a rat ischemic skin flap model that permits a prolonged reduction of blood flow resulting in wounds that become ischemic and resemble a chronic wound phenotype (reduced vascularization, increased inflammation and delayed wound closure). It consists of a bipedicled dorsal flap with 2 ischemic wounds placed centrally and 2 non-ischemic wounds lateral to the flap as controls. A novel addition to this ischemic skin flap model is the placement of a silicone sheet beneath the flap that functions as a barrier and a splint to prevent revascularization and reduce contraction as the wounds heal. Despite the debate of using rats for wound healing studies due to their quite distinct anatomic and physiologic differences compared to humans (i.e., the presence of a panniculus carnosus muscle, short life-span, increased number of hair follicles, and their ability to heal infected wounds) the modifications employed in this model make it a valuable alternative to previously developed ischemic skin flap models.

The rat, due to its size, availability, and rather docile behavior, has been utilized as a research model for many years. The goal of this protocol is to utilize the rat as an ischemic skin wound healing model to provide valuable insight into the pathophysiology of chronic wounds.

The propensity for chronic wounds in humans increases with ageing, disease conditions such as diabetes and impaired cardiovascular function, and ...

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies.
Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important.
The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

This protocol induces acute lung injury in a mouse that has close fidelity to the pathogenesis of acid pneumonitis observed in humans. We generate a maximal acute nonlethal low pH lung injury and account for differences in rodent-human anatomic respiratory structure using an open tracheostomy coupled with circumferential pressure release.

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute ...

Setting Up a Stroke Team Algorithm and Conducting Simulation-based Training in the Emergency Department - A Practical Guide

Time is of the essence when caring for an acute stroke patient. The ultimate goal is to restore blood flow to the ischemic brain. This can be&#160;achieved by either&#160;thrombolysis with recombinant tissue-plasminogen activator (rt-PA), the standard therapy for stroke patients who present within the first hours of symptom onset without contraindications, or by an endovascular approach, if a proximal brain vessel occlusion is detected. As the efficacy of both therapies declines over time, every minute saved along the way will improve the patient&#39;s outcome.
This critical situation requires thorough work and precise communication with the patient, the family and colleagues from different professions to acquire all relevant information and reach the right decision while carefully monitoring the patient. This is a high fidelity situation. In nonmedical high-fidelity environments such as aviation, Crew Resource Management (CRM) is used to enhance safety and team efficiency.
This guide shows how a Stroke Team algorithm, which is transferable to other hospital settings, was established and how regular simulation-based trainings were performed. It requires determination and endurance to maintain these time-consuming simulation trainings on a regular basis over the course of time. However, the resulting improvement of team spirit and excellent door-to-needle times will benefit both the patients and the work environment in any hospital.
A dedicated Stroke Team of 7 persons who are notified 24/7 by a collective call via speed dial and run a binding algorithm that takes approximately 20 min, was established. To train everybody involved in this algorithm, a simulation-based team training for all new Stroke Team members was conceived and conducted at monthly intervals. This led to a relevant and sustained reduction of the mean door-to-needle time to 25 min, and enhanced the feeling of stroke readiness especially in junior doctors and nurses.

Every min counts in acute stroke care. This guide shows how to establish a Stroke Team algorithm and enhance its performance with regular simulation training. The principles of Crew Resource Management (CRM) facilitate a straight workflow, reduce door-to-needle times and increase staff satisfaction.

Time is of the essence when caring for an acute stroke patient. The ultimate goal is to restore blood flow to the ischemic brain. This can ...

Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of metabolic syndrome (MetS)-related heart failure with preserved ejection fraction (HFpEF). The prevalence of MetS-related HFpEF is rising, and atrial cardiomyopathies associated with atrial remodeling and atrial fibrillation are clinically highly relevant as atrial remodeling is an independent predictor of mortality. Studies with isolated single-cell cardiomyocytes are frequently used to corroborate and complement in vivo findings. Circulatory vessel rarefication and interstitial tissue fibrosis pose a potentially limiting factor for the successful single-cell isolation of ACMs from animal models of this disease.
We have addressed this issue by employing a device capable of manually regulating the intraluminal pressure of cardiac cavities during the isolation procedure, substantially increasing the yield of morphologically and functionally intact ACMs. The acquired cells can be used in a variety of different experiments, such as cell culture and functional Calcium imaging (i.e., excitation-contraction-coupling).
We provide the researcher with a step-by-step protocol, a list of optimized solutions, thorough instructions to prepare the necessary equipment, and a comprehensive troubleshooting guide. While the initial implementation of the procedure might be rather difficult, a successful adaptation will allow the reader to perform state-of-the-art ACM isolations in a rat model of MetS-related HFpEF for a broad spectrum of experiments.

Here, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes from a rat model of metabolic syndrome-related heart failure with preserved ejection fraction. A manual regulation of intraluminal pressure of cardiac cavities is implemented to yield functionally intact myocytes suitable for excitation-contraction-coupling studies.

In this article, we describe an optimized, Langendorff-based procedure for the isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of ...