1. Introduzione I defibrillatori cardioverter impiantabile (ICD) prevenire la morte cardiaca improvvisa (SCD) nei pazienti sopravvissuti dopo la SCD oa rischio di morte cardiaca improvvisa a causa della compromissione della funzione ventricolare sinistra. Tuttavia, il pericolo delle terapie è elevato, in particolare monocamerali dispositivi. Queste scariche elettriche superflue possono essere nocive e ridurre la qualità della vita dei pazienti. Rivelazione atriale può migliorare le prestazioni del dispositivo e ridurre il rischio di shock inappropriato. 1,2 rilevazione atriale richiede tuttavia un elettrodo atriale che in sé comporta un rischio significativo associato. 3 Un produttore, BIOTRONIK, ha sviluppato un singolo elettrodo camera ventricolare con atriali capacità di rilevamento. Il primo elettrodo era Kainox A +, che ha rivelato eccellenti capacità di rilevamento. 4 Tuttavia, non è stato comunemente usato a causa di rigidità elettrodo e grande diametro (3,5 mm, 10,5 F). Ulteriori sviluppi della presente elettrodopiombo e alla creazione di piombo DX smart Linox S, che ha un diametro minore (2,6 mm, 7,8 F) e illustra caratteristiche impianto eccellenti capacità di rilevamento. 5 Questo documento illustra il posizionamento di questo elettrodo, per evidenziare i dati dallo studio master e per dimostrare sia la facilità di impianto e delle eccellenti capacità di rilevamento di questo elettrodo. 2. Caso Presentazione <ol><li> Il paziente era di 40 anni, fumatore femminile con una storia di malattia coronarica (CAD), recidiva di infarto miocardico anteriore (AMI) Stato-post intervento coronarico percutaneo (PCI), alterata funzione ventricolare sinistra (LVEF = 25%), ipercolesterolemia e la fibrillazione atriale parossistica (PAF). </li><li> Quattro mesi fa, la terapia medica per lo scompenso cardiaco è stato avviato. Il suo regime incluso beta-bloccanti, ACE-inibitori e diuretici, tuttavia, non vi era alcun miglioramento della funzione ventricolare sinistra. </li><li>Grazie alla sua significativa compromissione della funzione ventricolare sinistra, il paziente era ad alto rischio di morte cardiaca improvvisa (SCD). </li><li> Su presentazione, il paziente era in ritmo sinusale con perdita di onde R nelle derivazioni del torace. A 24 ore Holter ha rivelato a 32 minuti di episodio di fibrillazione atriale. </li><li> La decisione è stata presa di impiantare un ICD monocamerale, con capacità di rilevamento atriale al fine di monitorare ulteriori episodi di fibrillazione atriale e per evitare una terapia inappropriata in un paziente altrimenti molto attivo. </li></ol> 3. Diagnosi, valutazione, e Piano <ol><li> Il piano di trattamento era quello di impiantare una Lumax VR-T DX con un defibrillatore Linox piombo BIOTRONIK intelligente S DX sotto anestesia regionale in laboratorio elettrofisiologico. </li><li> Un eco transtoracica è stata eseguita prima dell&#39;impianto, al fine di rivalutare frazione di eiezione ventricolare sinistra e di escludere un trombo ventricolare, che potrebbero proibiretest defibrillatore durante l&#39;impianto. </li></ol> 4. Procedura di impianto <ol><li> Peri-procedurale preparazione inclusa una singola dose endovenosa di profilassi con antibiotici ed eparina sottocutanea. La terapia antitrombotica è stato mantenuto perché il rischio di un evento coronarico superato il rischio di sanguinamento durante la procedura </li><li> Il paziente è stato opportunamente preparato e avvolta in maniera sterile. </li><li> Il paziente è stato posto sotto sedazione moderata, con un monitoraggio appropriato, compreso il monitoraggio continuo elettrica cardiaca, pulsossimetria continua e monitoraggio non invasivo della pressione arteriosa. </li><li> Sedazione somministrata consisteva di midazolam, fentanyl e propofol IV con giudiziosa applicazione di un anestetico locale. </li><li> L&#39;impianto è iniziata con puntura della vena succlavia sinistra attraverso la cute intatta e il posizionamento di un filo nella vena cava inferiore (IVC). La posizione è stata confermata da X-Ray. Questo approccio inconsueto è stato utilizzato poiché la maggior parte elettrofisiologi interventistiche sono più esperti in questo approccio transcutaneo, piuttosto che l&#39;approccio più laterale della puntura della vena dalla tasca. </li><li> La pelle è stata tagliata con un bisturi circa 2 centimetri sotto e parallelamente alle clavicole. Dopo la tasca per il dispositivo è stato preparato sotto la clavicola sinistra, il filo nella vena è stata richiamata la tasca e un 8 guaina francese ha introdotto con la tecnica Seldinger. </li><li> L&#39;elettrodo è stato quindi introdotto nel SVC attraverso la guaina all&#39;atrio destro. Dopo un mandrino curvo (S 65-K, Biotronik) è stata introdotta l&#39;elettrodo, l&#39;elettrodo è stato spinto attraverso la valvola tricuspide al tratto efflusso del ventricolo destro. </li><li> Un mandrino diritta (S 65-C, Biotronik) è stato quindi introdotto l&#39;elettrodo. L&#39;elettrodo è sceso al ventricolo destro e inferiore, è stato manovrato per l&#39;apice del ventricolo destro. La posizione della punta dell&#39;elettrodo nonché generale posizione dei due elettrodi nell&#39;atrio è stato monitorato da X-ray. I due elettrodi ad anello atriale sono stati posti a livello della giunzione dell&#39;atrio SVC e destra. </li><li> Dopo l&#39;elettrodo è stato appropriatamente posizionato, misure dei segnali atriali e ventricolari sono state eseguite. </li><li> La soglia di stimolazione per l&#39;elettrodo ventricolare è stata misurata (Time in Video = &quot;07:27&quot;). Il segnale atriale è stata misurata tra 6,5 ​​e 8mV (Time in Video = &quot;07:56&quot;). Il segnale atriale è stata arricchita tre volte con l&#39;impostazione del filtro nel dispositivo. Il segnale ventricolare è stata misurata tra 8,4 e 9,5 mV. Con questi rilevamento e di stimolazione di soglia, l&#39;elettrodo è fissato all&#39;ingresso della vena succlavia. </li><li> L&#39;elettrodo è stato poi collegato al defibrillatore. </li><li> Tutte le misure sono stati ricontrollati e fibrillazione ventricolare è stata indotta da T-onde d&#39;urto tramite il defibrillatore e automaticamente risolto dal dispositivo. (Time in Video = &quot;11:01&quot;) </li><li> Il patdiale è stato portato al reparto ed è rimasto in ospedale fino al giorno seguente. Il post-operatorio giorno 1, i raggi X è stata presa per confermare la posizione del piombo e di escludere un pneumotorace. Soglie di rilevamento e di stimolazione sono stati ricontrollati ed erano simili alle misurazioni intraoperatorie. Il paziente è stato osservato per circa 4 ore in recupero ed è stato monitorato anche dopo l&#39;impianto. Nel complesso, l&#39;impianto ha avuto successo e la paziente è stata dimessa dall&#39;ospedale il giorno successivo. I primi tre mesi di follow-up era priva di eventi e segnali di rilevamento è rimasto stabile su questo lasso di tempo. </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>

Produzione e l&#39;accesso gratuito di questo video-articolo è sponsorizzato da BIOTRONIK.

L&#39;impianto di elettrodi DX nuovo Linox SMART S insieme con la Lumax ICD DX, Biotronik, è stato facile come il posizionamento di una singola camera di ICD. Questa esperienza è supportata da dati dal master inedito DX-trial. 5 Il Linox SMART elettrodo S DX offre il vantaggio di sensing atriale, senza lo svantaggio di un elettrocatetere atriale. Il segnale atriale è stata stabile nel tempo nel nostro paziente, come è stato dimostrato nel DX-trial. 5 Dispositivi bicamerali hanno dimostrato superiorità sul single-camera di rilevazione solo in uno studio prospettico randomizzato, chiamato il 1 +1 prova. 1 In questo studio, i pazienti con lento VT sono stati impiantati con un ICD bicamerale che si sia programmato per dual- o single-camera di rilevazione. L&#39;endpoint combinato era il numero di terapie inappropriate in risposta a SVT e VT al di sotto del tasso di rilevamento. Per questo endpoint, il 1 +1 trial ha dimostrato la significant superiorità della bicamerale (DCH), di rilevamento con un lungo intervallo di rilevazione tachicardia (TDI) rispetto al convenzionale programmata single-camera (SCH) di rilevamento. Questo risultato è stato rivisitato da Deisenhofer et al., Che ha randomizzato i pazienti a DCH-SCH o impianto di ICD. Tuttavia, il loro processo non rivolgersi in particolare pazienti con TV lente come la media intervallo di rilevamento tachicardia era 368 ms, e ha concluso che singolo e dispositivi bicamerali sono ugualmente efficaci per la terapia in pericolo di vita tachiaritmie ventricolari. Dispositivi DCH hanno mostrato avere classificazione superiore ritmo, ma non erano diverse dispositivi SCH in termini di riduzione terapie appropriato durante SVT. 6 Nonostante i vantaggi di una camera doppia ICD per la diagnosi e la differenziazione di tachicardie, il concetto di impiantare esso solo scopo di il rilevamento non è generalmente accettata, in quanto il rilevamento migliorato è controbilanciato dal rischio di complicità piomboni, nonché aumento della mortalità e morbilità. 2,7,8 Pertanto, il miglioramento della tecnica di impianto o di un VDD-sistema di rilevamento doppia camera è necessario. 9,10. L&#39;elettrodo DX SMART Linox S DX combinata con la Lumax ICD offre questo vantaggio. Le strutture di rilevamento sono simili a un dispositivo a camera doppia e la percentuale di complicanze è basso quanto in convenzionali ICD monocamera. 5 Conclusione La Lumax VR-T DX è stata dimostrata affidabile per rilevare i segnali atriali e raccogliere preziose informazioni per consentire la diagnosi precoce di aritmie atriali. Inoltre, il dispositivo offre la discriminazione AV con SMART per la riduzione scosse sicuro. I canali disponibili atriale diagnosi IEGM l&#39;adeguatezza di rilevamento ICD e terapia, riducendo gli shock inappropriati e di ottenere informazioni per ottimizzare la programmazione del dispositivo.

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

I defibrillatori cardioverter impiantabili (ICD) interrompere la tachicardia ventricolare (VT) e la fibrillazione ventricolare (FV) con elevata efficacia e può proteggere i pazienti da morte cardiaca improvvisa (SCD). Tuttavia, gli shock inappropriati si può verificare se le tachicardie sono mal diagnosticati. Gli shock inappropriati sono dannosi e ridurre la qualità della vita dei pazienti. Il rischio di terapia inappropriata aumenta con tassi di rilevazione più bassi programmate nel ICD. Singola camera di rilevazione comporta maggiori rischi per una diagnosi errata se confrontata con dispositivi bicamerali che hanno il beneficio di ulteriori informazioni atriale. Tuttavia, utilizzando un dispositivo a doppia camera solo scopo di rilevamento non è generalmente accettata, poiché i rischi associati con il secondo elettrodo può superare i vantaggi di rilevamento. Pertanto, BIOTRONIK sviluppato un conduttore ventricolare chiamato Linox SMART S DX, che consente il rilevamento di segnali atriali da due elettrodi posizionati nella parte atriale del the ventricolare elettrodo. Questo dispositivo comprende due elettrodi ad anello, uno che contatta la parete atriale alla giunzione della vena cava superiore (SVC) e uno posizionato in corrispondenza della parte libera fluttuante dell&#39;elettrodo nell&#39;atrio. L&#39;eccellente qualità del segnale può essere raggiunto solo da un ambiente speciale filtro nella ICD (Lumax 540 e 740 DX VR-T, BIOTRONIK). Qui, la facilità di impianto del sistema sarà dimostrato.

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-camera dei defibrillatori impiantabili cardioverter (ICD) può migliorare il rilevamento della fibrillazione atriale e la differenziazione delle tachicardie. Tuttavia, questo vantaggio viene compromessa da complicazioni associate con il secondo elettrodo, che è richiesta in dispositivi convenzionali doppia camera. Pertanto, BIOTRONIK ha sviluppato un nuovo elettrodo chiamato Linox<sup&gt; SMART</sup&gt; S DX che, quando usato in combinazione con il DX Lumax ICD, offre doppia camera di rilevazione senza i rischi associati con il secondo elettrodo.

Un nuovo defibrillatore impiantabile Camera singola con Sensing atriale: una dimostrazione pratica di rilevamento e di facilità di impianto

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-camera dei defibrillatori impiantabili cardioverter (ICD) può migliorare il rilevamento della fibrillazione atriale e la differenziazione delle tachicardie. Tuttavia, questo vantaggio viene compromessa da complicazioni associate con il secondo elettrodo, che è richiesta in dispositivi convenzionali doppia camera. Pertanto, BIOTRONIK ha sviluppato un nuovo elettrodo chiamato Linox SMART S DX che, quando usato in combinazione con il DX Lumax ICD, off...

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.

Ablazione transcatetere in combinazione con i tasti chiusura appendice atriale per la fibrillazione atriale

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

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Medicina

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.

Rapid Point-of-Care test di efficacia anticoagulante Enoxaparina nel sangue intero

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.

Tecnica chirurgica per la consegna del midollo spinale per le terapie: Dimostrazione di procedura a Gottinga nel maialino

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.

Un nuovo modello murino di endovascolare aneurisma dell&#39;aorta riparazione

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.

Costruzione di vapore Chambers utilizzato per esporre topi da alcol Durante l&#39;equivalente di tutti i tre trimestri di Sviluppo Umano

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.

Modello murino di dall&#39;arteria femorale Wire Injury con impianto di una Perivascolare Drug Delivery Patch

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.

Dimostrazione del Topo ischemica pelle ferita Modello

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.

Aprire tracheostomia gastrico acido aspirazione Modello murino di lesioni polmonari acute Risultati in massima acuta non letale 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 ...

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.

Impostazione di una Stroke algoritmo squadra e svolgono la formazione basata sulla simulazione nel Dipartimento di Emergenza - Una guida pratica

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.

Isolamento dei cardiomiociti atriali da un modello del ratto di metabolico sindrome-relativo infarto con la frazione conservata di espulsione

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