Chronic aortic root pressure-loading assessment model.

PURPOSE: Percutaneous placement of transcatheter prosthetic aortic valves without cardiopulmonary bypass (CPB) continues to gain clinical acceptance. However, information on pressure-loading characteristics of the aortic root/annular areas is limited. For this reason, we designed a preclinical model, implanting an aortic root load transducer with a power source/telemetry system for chronic, conscious, loading data acquisition. This research study was conducted to determine whether an animal model could accurately measure in vivo loading. METHODS: Preoperatively, echocardiography and magnetic resonance imaging were used to determine both aortic annular and sinotubular junction dimensions, as well as ascending aortic length. Six adult sheep were placed on CPB, aortic root and ascending aorta were skeletonized and the origins of both coronary ostia were identified. Cardiac arrest with myocardial protection with cold coronary blood cardioplegia was instituted. A properly sized aortic root load-sensing device, consisting of a transcatheter aortic valve with a ring load transducer was implanted via a left apical ventriculotomy. Verification of position was determined before closure of the ventriculotomy. Each animal was weaned from CPB, and closed in routine fashion with the power source of the device placed in a subcutaneous pocket. RESULTS: There were no operative deaths or significant postoperative complications. Serial pressure-load sensing assessments in a conscious state produced reproducible proprietary data. CONCLUSIONS: This animal model allowed successful serial pressure-load sensing assessment of the aortic root/annular areas, providing a better physiological understanding of these anatomical inter-relationships. This added information could aid in future device designs with potential improved clinical outcomes.

Surgical approaches to vascular access for large-caliber devices in preclinical research models.

Percutaneous vascular access options in preclinical models are often smaller than the relevant structures in humans or undersized for early-prototype research devices. Here we describe the surgical approaches and results for surgical vascular access sites in preclinical swine and sheep models. Fourteen adult miniature swine underwent successful 18-French vascular access by means of thoracotomy to the brachiocephalic artery. In addition, 11 swine and 10 sheep underwent successful 22-French vascular access by means of retroperitoneal laparotomy to the abdominal aorta. The relevancy of approach angles and vessel tortuosity should be considered when selecting appropriate preclinical models and techniques. The techniques described are effective for delivery of large-caliber devices in preclinical testing.

Phasic coronary blood flow patterns in dogs vs. pigs: an acute ischemic heart study.

BACKGROUND: Canine and porcine hearts have been widely used to investigate diagnoses, interventions, and surgical therapies for ischemic heart disease. Dogs and pigs are known to vary with regard to the anatomic distribution of their coronary arteries. However, the mechanisms of these differences and the differing phasic coronary blood flow patterns between the two species are not well characterized. MATERIAL/METHODS: Phasic coronary blood flow patterns and hemodynamic data were analyzed using three flow probes placed around the left anterior descending (LAD), left circumflex (LCX), and right coronary (RCA) arteries in both canine and porcine models. RESULTS: Systolic left ventricular pressure, arterial pressure, and systemic vascular resistance in dogs were higher than in pigs. Likewise, total coronary blood flow, LAD flow, and LCX flow were higher in dogs than in pigs. LCX flow was higher in dogs, but RCA flow was higher in pigs. Diastolic fraction and diastolic/systolic peak velocity ratio of the LAD, LCX, and RCA showed no significant differences at baseline between dogs and pigs. Systolic LAD flow in dogs decreased after the creation of an LAD stenosis, whereas systolic LAD flow in pigs increased. CONCLUSIONS: Coronary blood flow patterns in dogs and pigs are quite different. These findings are potentially relevant to understanding the physiology of myocardial blood perfusion in dogs and pigs with ischemic heart disease.

Acute reduction of functional mitral regurgitation in canine model using an epicardial device.

PURPOSE: This study evaluated the short-term feasibility of a novel epicardial device that treats functional mitral regurgitation by simultaneously changing the mitral and the left ventricular geometry. DESCRIPTION: We implanted a prototype device that consists of 2 tissue anchors, a deflector, and a flexible tightening chord in 7 mongrel dogs with heart failure and functional mitral regurgitation induced by rapid ventricular pacing. Hemodynamic and echocardiographic data were obtained before and after device implantation. EVALUATION: The device acutely reduced the mitral regurgitation grade from 3.2 +/- 0.3 to 0.9 +/- 0.5 (p < 0.001). Left ventricular end-diastolic volume (79.6 +/- 23.6 to 61.2 +/- 16.9 mL; p = 0.004) and end-systolic volume (63.1 +/- 17.3 to 49.2 +/- 12.3 mL; p = 0.006) decreased substantially. End-systolic elastance significantly increased from 1.9 +/- 1.0 to 2.6 +/- 1.4 mm Hg/mL (p = 0.02). Device implantation did not alter coronary perfusion. CONCLUSIONS: The epicardial device acutely reduced functional mitral regurgitation and improved left ventricular geometry. Further studies are required to demonstrate the long-term safety and efficacy of this concept.

Beating heart cardioscopy: a platform for real-time, intracardiac imaging.

PURPOSE: The purpose of this study was to develop a method for real-time, fiberoptic, intracardiac imaging to serve as a platform for closed-chest, intracardiac surgery on the beating heart. DESCRIPTION: Fiberoptic cardioscopy of the left and right heart was conducted in a porcine model. A cardiopulmonary bypass circuit maintained systemic organ perfusion and a separate circuit replaced intracardiac blood with oxygenated, modified Krebs-Henseleit perfusate. EVALUATION: Video images of structures in the left and right sides of an in vivo beating heart were obtained, including the inner surface of the left and right atria and ventricles, the mitral and aortic valves, the Thebesian veins, and the coronary sinus. Effective isolation of the heart from systemic and intracardiac blood flow and control of perfusion rates were important factors for successful image acquisition. CONCLUSIONS: Fiberoptic cardioscopy is a novel approach that allows for visualization of the structures within a nonarrested heart on bypass. It lays the groundwork for a platform that could lead to more successful percutaneous valvular and intracardiac procedures in a stable hemodynamic environment.

Hemodynamic and metabolic changes during exercise in calves with total artificial hearts of different sizes yet similar output.

To evaluate the effects of downsizing of the total artificial heart (TAH), we compared the anaerobic threshold (AT) values in calves with two different types of TAH (Cleveland Clinic-Nimbus TAH and the downsized MagScrew TAH). Exercise studies were performed using a treadmill in 12 calves. During the exercise, parameters to obtain the AT were measured. To evaluate the determinants of the AT, a linear regression analysis was performed between AT and potential variables. AT values from 29 studies revealed no significant differences between the two different TAHs, with no significant differences in hemodynamic or oxygen metabolic parameters. AT values correlated well with pump flow/body weight (Q) multiplied by the hemoglobin level, regardless of the TAH used. In conclusion, downsizing of the original TAH design did not reduce AT without any significant differences in hemodynamic or oxygen metabolic parameters during exercise in calves.

Cadaver fitting study of the DexAide right ventricular assist device.

The DexAide right ventricular assist device (RVAD) has been developed to provide an implantable RVAD option to surgeons. The aim of this study was to determine the optimal cannula design and optimal implantation location of the DexAide RVAD in preparation for its clinical use. Separately, a HeartMate XVE left ventricular assist device (LVAD) and CorAide LVAD models were implanted into the preperitoneal and right thoracic space, and the anatomical fit of the DexAide RVAD was evaluated in five preserved human cadavers. The DexAide RVAD inflow cannula was inserted through the diaphragmatic surface of the right ventricle and the outflow was directed to the pulmonary artery. Right thoracic implantation of the DexAide RVAD provided an excellent fit with either the HeartMate or CorAide LVAD in all cadavers. The results of this study will guide improvements in the designs of cannulae and implantation of the DexAide RVAD in future clinical applications.

Cleveland Clinic PediPump lamb cadaver fitting studies.

We are developing the PediPump, a magnetically suspended, mixed-flow pump, as an implantable pediatric ventricular assist device (VAD). Lamb cadaver fitting studies were performed to determine the optimal pump location and optimal design of the inflow and outflow conduits for chronic in vivo studies. A prototype of the PediPump right and left ventricular assist devices (RVAD and LVAD, respectively) were implanted via a sternotomy or left thoracotomy in four lamb cadavers (3.7-34.2 kg). Via a sternotomy, the RVAD and LVAD required long inflow cannulas when placed into the right or left thoracic cavities, respectively. Via a left thoracotomy, with both pumps implanted in the left thoracic cavity, the RVAD required a 70 degrees inflow cannula and a bent outflow graft while the LVAD required a 130 degrees inflow cannula and a straight outflow graft. In conclusion, left thoracotomy provided optimal fitting for both LVAD and RVAD for the small lamb model.

Acute in vivo evaluation of a new stentless mitral valve.

OBJECTIVES: We have developed a stentless pericardial mitral valve prosthesis in 2 configurations; the purposes of this acute study in sheep were to assess (1) valve design and implant technique; (2) valve performance; and (3) acute effects on postimplant left ventricular function. METHODS: A stentless bovine pericardial bileaflet valve was developed with the intent to preserve annular-papillary muscle continuity. This valve, in 2 configurations-with (n = 5) and without (n = 5) flap chordae-was implanted in 10 sheep (mean weight 73 +/- 9 kg). Epicardial echocardiography was performed to assess valve performance. Load-independent left ventricular function was also estimated before implantation (baseline), 1 hour after discontinuing cardiopulmonary bypass (rest), and during dobutamine stimulation using conductance technology. RESULTS: Implantation was easily accomplished for both configurations. Both configurations had low transvalvular pressure (mean 2.1 +/- 1.2 mm Hg at rest; 2.2 +/- 1.0 mm Hg with dobutamine stimulation with flap chordae; 1.7 +/- 0.5 mm Hg and 1.6 +/- 0.3 mm Hg without flap chordae). No mitral regurgitation was observed in 8 sheep, and mild regurgitation was seen in 2 sheep. Compared with baseline, slope of maximum rate of change of left ventricular pressure-end-diastolic volume relation increased with stimulation both with flap chordae (+52 +/- 41 mm Hg x s(-1)x mL(-1), P = .0005) and without (+20 +/- 12 mm Hg x s(-1) x mL(-1), P = .003). CONCLUSIONS: Both configurations of this newly designed stentless mitral bioprosthesis, which preserves annular-papillary muscle continuity using different novel surgical implantation techniques, demonstrated reliable valve performance, with low transvalvular pressure gradients, minimal regurgitation, and acutely preserved postimplant left ventricular function. Further chronic study is needed to verify these results and evaluate reliability of implantation procedures, biocompatibility, and durability.

Impact of left atrial appendage exclusion on left atrial function.

OBJECTIVES: We sought to investigate the short-term and midterm effects of left atrial appendage exclusion on left atrial function. Left atrial appendage exclusion is considered a possible therapeutic option for stroke prevention in patients with atrial fibrillation. Favorable outcomes have encouraged widespread use of left atrial appendage exclusion for cardiac surgical patients-even for patients in sinus rhythm who have stroke risk factors; however, the chronic effects on left atrial function of left atrial appendage exclusion are unclear. METHODS: Nineteen mongrel dogs (29.7 +/- 5.2 kg) in sinus rhythm were studied. The Doppler signals from the pulmonary venous flow, transmitral flow, and tissue Doppler imaging of mitral annular motion were obtained before and after left atrial appendage exclusion. Dogs were evaluated in the same manner at 7 days (n = 2), 30 days (n = 7), or 90 days (n = 10) after left atrial appendage exclusion. RESULTS: Except for a significant increase in early diastolic transmitral flow velocity after left atrial appendage exclusion (P = .01), no significant differences were found in any parameters related to the transmitral flow and tissue Doppler imaging measurements throughout follow-up. The systolic components of pulmonary venous flow at follow-up revealed a significant reduction relative to baseline (peak systolic velocity P < .0001, systolic velocity-time integral P < .0001), despite the lack of significant changes in left atrial pressure, left ventricular volume, and stroke volume. CONCLUSION: Left atrial appendage exclusion may affect left atrial reservoir function in the short-term and midterm periods. Further long-term studies with more clinically relevant models are needed.

Ventral cardiac denervation increased right coronary arterial blood flow.

BACKGROUND: Cardiac denervation accompanied with coronary artery bypass surgery has been widely performed for the treatment of vasospastic angina associated with atherosclerotic coronary artery disease. However, the effect of cardiac denervation on phasic coronary blood flow patterns of the left anterior descending coronary artery (LAD), left circumflex coronary artery (LCX) and right coronary artery (RCA) remains unknown. This study aimed to investigate the effect of cardiac denervation on phasic coronary blood flow patterns of the LAD, LCX and RCA. METHODS: Phasic coronary blood flow patterns were analyzed using three flow probes placed around the LAD, LCX and RCA with and without LAD stenosis. Ventral cardiac denervation (VCD) was performed in 8 pigs, and 16 pigs were used as control subjects. Autonomic activities before and after the VCD were quantified by wavelet analysis of heart rate variability. RESULTS: The mean LAD flow (34.4+/-9.4 to 32.6+/-7.1 ml/min, p=0.638) and mean LCX flow (26.3+/-10.2 to 27.2+/-6.0 ml/min, p=0.825) showed no significant change after VCD, while the mean RCA flow (31.3+/-9.0 to 38.2+/-11.2 ml/min, p=0.003) significantly increased. The hemodynamic variables in the VCD group were well maintained after creation of LAD stenosis, while they deteriorated in the control group. The low-frequency components, high-frequency components and their ratio did not change after VCD. CONCLUSIONS: VCD prevented the deterioration of cardiac function after creation of an LAD stenosis and resulted in an increase of the mean RCA flow. VCD did not affect autonomic nervous system activity.

Progress in the development of the DexAide right ventricular assist device.

The DexAide right ventricular assist device (RVAD) is an implantable centrifugal pump modified from the CorAide left ventricular assist device. As previously published, in vitro performance testing of the DexAide RVAD has met design criteria, and the nominal operating condition of 4 l/min and 20 mm Hg pressure rise was achieved at 2,000 rpm, with a power consumption of 1.9 watts. In vivo studies in 14 calves have demonstrated acceptable hemodynamic characteristics. The calf inflow cannula design is still evolving to minimize depositions on the cannula observed in most experiments. Fitting studies were performed in 5 cadavers and 2 patients to reconfigure the cannulae for use in humans. The design and development of external electronics have been completed for the stand-alone RVAD system, and verification tests are under way in preparation for preclinical tests. Work on the external electronics design for the biventricular assist system is ongoing. In conclusion, the initial in vitro and in vivo studies have demonstrated acceptable hemodynamic characteristics of the DexAide RVAD. The design and development of the external electronic components for the stand-alone RVAD system have been completed. The calf inflow cannula is being redesigned, and chronic in vivo tests are under way.

The PediPump: development status of a new pediatric ventricular assist device: update II.

The PediPump is a new ventricular assist device with a hydraulic output range designed for children from newborn infants to adolescents. The design is based on a mixed-flow rotary pump; the rotating assembly consists of a front impeller, front and rear radial magnetic bearings, and a central motor magnet. Two different implantable pumps were designed initially: an intravascular pump measuring 7 x 75 mm and an extravascular pump measuring 14 x 85 mm. Current prototypes are substantially smaller: The current intravascular version measures 4.5 x 55 mm, whereas the current extravascular version measures 11 x 70 mm. Both devices provide pressure and flows capable of supporting adults, far exceeding the initially defined physiologic requirements for children weighing 2 to 25 kg. This basic pump design may be used in acute or chronic clinical settings to provide right ventricular, left ventricular, or biventricular support. There are three objectives for the PediPump development program: 1) determination of basic engineering requirements for hardware and control logic including design analysis for system sizing, evaluation of control concepts, and bench testing of prototypes; 2) performance of preclinical anatomic fitting studies using CT-based 3D modeling; and 3) animal studies to provide characterization and reliability testing of the device.

Replacement of the left-side valves of an implanted total artificial heart.

The MagScrew total artificial heart (TAH) is under development. Despite its anticipated durability and reliability, the possibility of a bioprosthetic valve malfunction exists. As a result, the potential for valve replacement surgery, instead of device replacement, would be desirable after a TAH implant. In two of our 90-day animal experiments, we successfully replaced the left-side valves through a left thoracotomy opposite to the right-sided incision site for the initial TAH implant. The results of these cases suggest that the left-side valves could also be replaced through a left thoracotomy approach in humans. To confirm the ability to access the left-side valves in humans, four human cadaver studies were performed with the use of a mock pump designed for human application. This report describes the operative techniques for left-side valve replacement in animals and discusses the advantages of a left thoracotomy in clinical situations, based on results from the human cadaver studies.

Evaluation of a novel device for left atrial appendage exclusion: the second-generation atrial exclusion device.

BACKGROUND: The left atrial appendage is a frequent source of thromboemboli in patients with atrial fibrillation. Exclusion of the left atrial appendage may reduce the risk of stroke in patients with atrial fibrillation. The atrial exclusion device, previously developed to perform left atrial appendage exclusion on a beating heart, was modified to accommodate different anatomic patterns of the human left atrial appendage and to ensure uniform pressure and occlusion. The purpose of this study was to evaluate this second-generation atrial exclusion device during a midterm period in a canine model. METHODS: Ten mongrel dogs (mean weight 28.9 +/- 4.6 kg) were used in this study. The atrial exclusion device, constructed from two parallel and rigid titanium tubes and two nitinol springs with a knit-braided polyester fabric, was implanted at the base of the left atrial appendage through a left thoracotomy on a beating heart using a specially designed delivery tool. Dogs were evaluated at 30 days (n = 4) and 90 days (n = 6) by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histologic inspection. RESULTS: Device implantation was performed without complications in all dogs. Complete left atrial appendage exclusion without device migration or hemodynamic instability was confirmed, and there was no damage to the left circumflex artery or pulmonary artery. Macroscopic and microscopic assessments revealed favorable biocompatibility during midterm follow-up. CONCLUSION: The atrial exclusion device enabled rapid, reliable, and safe exclusion of the left atrial appendage. Clinical application may provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

Development of patient-specific three-dimensional pediatric cardiac models.

The availability of algorithms to create three-dimensional (3D) models from medical images has made it possible to render and build patient-specific reconstructions of individual body parts. In the present study, this technology was used to create 3D models of pediatric hearts for use in medical device development. Digital models were created using CT datasets of pediatric hearts and commercially available 3D image processing software. Using this software, stacked CT data were viewed, and pixels representing the heart and rib cage were selected and rendered as 3D models. Stereolithography and 3D printing technology were used to create rigid and flexible physical heart models (biomodels) from the digital models. Twelve on-screen models of the thorax and cardiac structures were created from cardiac CT scans obtained from 11 patients with and without congenital heart disease (median age, 3 years; range, 2 days to 13 years). Rigid and flexible physical heart models were generated from the digital models to provide tactile and visual information. 3D models of pediatric cardiac and chest anatomy provide enhanced understanding and tactile representation of complex anatomy. Precise representation of the spatial relationships between anatomic structures is particularly useful during the development and placement of medical devices.

Transmural distribution of myocardial blood perfusion and phasic coronary blood flow pattern in a canine model of acute ischemia.

BACKGROUND: Although several investigators have analyzed coronary artery blood flow under various conditions, almost all these studies have measured only some branches of the left anterior descending (LAD), left circumflex (LCX), or right coronary (RCA) artery. METHODS: In a canine model of acute ischemia (n = 5), we simultaneously assessed (a) regional myocardial blood perfusion using microspheres and (b) phasic coronary blood flow patterns as measured by three epicardial flow probes placed around the LAD, LCX, and RCA. RESULTS: The results from this study indicated that the LAD supplies blood to the epicardial (r = 0.687, p<0.0001), midwall (r = 0.556, p = 0.0021), and endocardial layers (r = 0.666, p = 0.0001) of the LAD area; the LCX supplies the midwall (r = 0.514, p = 0.0051) and endocardial layer (r = 0.621, p = 0.0004) of the LCX area, antero-lateral papillary muscle (r = 0.548, p = 0.0025), and postero-medial papillary muscle (r = 0.641, p = 0.0002), especially during the diastolic phase; and the RCA supplies the right ventricular apex (r=0.559, p=0.0020), left atrium (r = 0.618, p = 0.0005), right atrium (r = 0.471, p = 0.0114), and postero-medial papillary muscle (r = 0.486, p = 0.0088), especially during the systolic phase. CONCLUSIONS: These results are potentially relevant to understanding the physiology of myocardial blood perfusion and to improving treatment of acute myocardial ischemia and infarction.

Experimental study of new diagnostic system for coronary artery disease using coronary transit index.

OBJECTIVES: Noninvasive cardiac imaging techniques have had an increasing role in the diagnosis of coronary artery disease. However, these techniques are not widely available as a tool in the office setting. The purpose of this study was to provide an accurate assessment of coronary artery disease for screening purposes using Coronary Transit Index (CTI) assessment with small, high-resolution gamma cameras. METHODS: Total coronary blood flow was measured with ultrasonic flow probes placed around the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery in a total of 33 conditions in 5 healthy mongrel dogs. The coronary blood flow was reduced stepwise with vascular occluders placed around the coronary arteries. The procedure for obtaining CTI included 4 parts: 1) The animal was injected intravenously with a bolus of a radioactive tracer (2.5-5.0 mCi of (99m)Tc-DTPA); 2) Dedicated gamma sensors monitored the passage of the injected bolus; 3) Time-activity curves were measured at the left ventricle with and without its wall; 4) The ratio of the washout rates of the 2 curves determined the CTI. RESULTS: Coronary Transit Index was successfully obtained from the left ventricle. The coronary blood flows measured by flow probes were well correlated with the regional myocardial blood flow. The percentage of the baseline value of the total coronary blood flow had the highest correlation (R=0.807, p<0.0001) with the Coronary Transit Index. CONCLUSIONS: These data indicated that a new diagnostic system using CTI successfully identified reduced coronary blood flow.

A novel technique for functional mitral regurgitation therapy: mitral annular remodeling.

BACKGROUND: Functional mitral regurgitation (AIR) plays a pivotal role in the pathophysiology of congestive heart failure, a major cause of cardiac morbidity and mortality. We have developed a mitral annular remodeling procedure through injection of a nonabsorbable substance into the peri-annular tissue of the posterior mitral annulus to reduce the mitral annular dimension in the septal-lateral axis. The purpose of this study is to describe a novel procedure for treatment of functional AIR and report its effects on the geometry of the mitral annulus and degree of AIR. METHODS: Seven preliminary studies were performed using an epicardial approach in a healthy dog model to establish the feasibility of this injection procedure. Unexpectedly, 2 of 7 healthy dogs had a functional AIR of grade 1 to 2+. In these 2 cases, the hemodynamic, angiographic, and echocardiographic assessments were conducted. RESULTS: A nonabsorbable substance injection was successfully performed on a beating heart without instability of hemodynamics or any evidence of myocardial ischemia in all 7 dogs. In the 2 dogs with a functional AIR, it was confirmed that the septal-lateral dimension decreased from 3.2 +/- 0.2 to 2.6 +/- 0.5 cm and the observed MR was reduced (AIR area from 1.2 +/-0.1 to 0 cm2) without any adverse effects on hemodynamics or coronary circulation (circumflex artery flow, 36.5 +/- 0.4 to 40.5 +/- 0.1 mL/min). CONCLUSION: Off-pump mitral annular remodeling through substance injection may be one procedural option for treatment of functional AIR.

Performance and reliability of the CPB/ECMO Initiative Forward Lines Casualty Management System.

The Cleveland Clinic Foundation CPB/ECMO Initiative Forward Casualty Management System is an economical, compact, transportable, disposable system designed to permit a rapid expansion of trauma management services requiring cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) pulmonary support. The system, composed of a rotary blood pump, a pump motor driver, and an electronic control console as the blood pumping subsystem, also includes commonly used compatible commercial oxygenators, venous reservoirs, and cannulae. In vitro durability testing accumulated over 100 hours without failure. In vivo reliability was tested in 10 calves under general anesthesia during 6 hours of CPB and ECMO under full heparinization at nominal operating conditions of 4-5 l/min and 2-4 l/min blood flow respectively, and mean arterial pressures between 65 and 100 mm Hg. A mean time to failure of 57 hours was reached during the animal series. Results of these test series demonstrated that this system has the capability to reliably operate during a 6-hour conventional CPB or ECMO procedure, while providing flexibility and ease of use for the operator.