Prosthetic heart valves undergo mandatory preclinical animal testing prior to human clinical trials. Historically, a non-site-specific placement of a valve prosthesis has been commonly performed; however, recently site-specific placement continues to attract interest. Various animal models have been used for preclinical evaluation of both aortic and mitral valve prostheses; however, a universally accepted animal model for orthotopic total aortic root replacement with acceptable early and late mortality for long-term evaluation has been lacking. This article reports a successful orthotopic model for placement of tissue valve conduit prosthesis for total aortic root replacement in adult sheep. This model utilized preoperative echocardiographic assessment, specific intraoperative surgical techniques, and both early and late postoperative management therapies. The combination of all of these components resulted in a successful model for orthotopic placement of a tissue valve prosthesis for total aortic root replacement in adult sheep for potential long-term assessment.

Background-Pharmacological ventricular rate control is an acceptable atrial fibrillation (AF) therapy limited by systemic toxicity. We postulate that focal catheter-based drug delivery into the atrioventricular nodal (AVN) region may effectively control ventricular rate during AF without systemic toxicity. This study evaluated the effects of focally administered acetylcholine on AVN conduction and refractoriness during sinus rhythm and AF. Methods and Results-Canines (nϭ7) were anesthetized and instrumented to assess cardiac electrophysiology and blood pressure. A custom drug delivery catheter was implanted in the AVN region. Incremental doses of acetylcholine starting at 10 g/min were infused until complete AV block was achieved. Acetylcholine induced dose-dependent AV block. AF induction and electrophysiology measurements were performed during baseline and acetylcholine-induced first-degree and third-degree AV block. During AF, infusion of acetylcholine decreased ventricular rates from 182Ϯ32 to 77Ϯ28 and 28Ϯ8 bpm (first-degree and third-degree AV block, respectively; PϽ0.05). At the first-degree AV block dose, AVN effective refractory period increased from 186Ϯ37 to 282Ϯ33 ms, and Wenckebach cycle length increased from 271Ϯ29 to 378Ϯ58 ms (PϽ0.05). The first-degree AV block dose prolonged AV and AH intervals by 26% and 23% (PϽ0.05), whereas AA intervals and blood pressure remained unchanged, demonstrating a local effect. All effects were reversed 20 minutes after infusion was stopped. Conclusions-Focal acetylcholine delivery into the AVN increased AVN refractoriness and significantly decreased ventricular rate response during induced AF in a dose-related, reversible manner without systemic side effects. This may represent a novel therapy for AF whereby ventricular rate is controlled with the use of an implantable drug delivery system. (Circulation. 2006;113:2383-2390.)Key Words: acetylcholine Ⅲ catheters Ⅲ conduction Ⅲ pharmacology Ⅲ tachyarrhythmias C urrent clinical treatment options for arrhythmias include pharmacotherapy, ablation, and medical devices. Although these therapeutic approaches may have some role in the treatment of atrial fibrillation (AF), the successful management of this disease remains an unmet clinical need. Ideally, AF should be treated by a strategy of prevention and, if needed, conversion of the arrhythmia to a regular sinus rhythm. However, pharmacological therapies typically fail to prevent AF, particularly in patients with structural heart disease. Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial and from other clinical trials suggest that AF management with the rhythm-control strategy offers no survival advantage over rate control and furthermore that rate control may be more advantageous (lower risk of adverse drug effects, lower number of hospitalizations, and lower healthcare burden). 1,2 For supraventricular tachyarrhythmias with fast ventricular response with origin of the focus in the atria, the most Editorial p 2374 Clinical Pers...

Computational models that incorporate human anatomy, tissue biomechanics, and experimental measurements from animals or cadavers to predict medical device performance have proven useful. Since implant choices made by clinicians and biological tissue properties can vary widely across patients, these models tend to suffer from a fundamental lack of information about such variations that impact the analysis. To demonstrate a new means of overcoming such paucity of input data, the authors focused on a tractable device concern (that of temporary continence care lead movement) and allowed input properties to vary within the bounds of experiment to generate many simulations that ultimately predicted device performance. The computational model results were then compared with experimental results to build confidence in the predictions. The results suggest that a new method considering intervals of poorly defined and highly variable biomechanical and structural modeling inputs can faithfully predict device mechanics as measured in a cadaver model. Moreover, both model and experiment suggest that a new basic evaluation lead can provide more reliable fixation compared to the predicate device.

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Patients born with congenital right ventricular outflow tract lesions are faced with invasive procedures to establish hemodynamic and physiological stability. Commonly, multiple subsequent surgical procedures are required due to deterioration of a previous repair. These procedures carry additive risks of mortality and morbidity. Less aggressive procedures with accompanying lower risk is ideal. Success in percutaneously placing a transcatheter valve has previously been reported; however, continued safety and efficacy of any technique needs continual assessment. We developed a model for preclinical evaluation of a percutaneous placement of a pulmonic transcatheter valve in adult sheep, including preoperative, surgical, and postoperative techniques for long-term evaluation. Adult sheep were assessed and determined to be acceptable for study enrollment. Perioperative antibiotics and analgesics were given prior to a left thoracotomy. A Medtronic, Hancock 1 valve conduit was inserted for reconstruction of the right ventricular outflow tract. The Hancock 1 valve conduit alone represented the control group and the test animals comprised the addition of a Melodytrade mark transcatheter pulmonary valve (TPV), within the Hancock 1 valve conduit. Fifteen adult sheep survived the surgical implant procedure with no perioperative mortality. There were four early postoperative deaths, three due to infection and one due to heart failure, secondary to intraoperative heart block. The remaining 11 animals remained healthy, gained weight, and survived to termination at 5 months. An initial definite-sized valve conduit was implanted, followed by inserting a single size TPV, which allowed a more accurate physiological assessment of any chosen valve. Our developed adult sheep model for percutaneous TPV implantation for right ventricular outflow tract lesions was successful for long-term assessment by utilizing our preoperative, surgical, and postoperative techniques.