Short-term in vivo performance of the Cleveland clinic PediPump left ventricular assist device.

The PediPump was implanted in six healthy lambs (mean 25.6 ± 1.4 kg) between the left ventricular apex and the descending aorta to evaluate in vivo performance for up to 30 days. Anticoagulation was achieved by continuous heparin infusion. Three animals were euthanized prematurely, two because of respiratory dysfunction and one because of deteriorating pump performance resulting from thrombus formation inside the pump. Three lambs were electively sacrificed 30 days after implantation; all had stable hemodynamics and minimal hemolysis, as indicated by low plasma free hemoglobin (2.5 ± 3.1 mg/dL). Mean 30-day pump flow was 1.8 ± 0.1 L/min at a pump speed of 12 200 ± 400 rpm. Neither activated clotting time nor activated partial thromboplastin time followed the changes in heparin dose. At necropsy, depositions were observed at the front (n = 1) and rear rotor axial positioning stops (n = 4); improved polishing techniques on the stationary stop surfaces and the addition of a hard-carbon, thin-film coating on the rotating stop of the pumps used for the last two experiments addressed the deposition seen earlier. In conclusion, the PediPump showed excellent hydraulic performance and minimal hemolysis during support for up to 30 days. Depositions observed at the axial positioning stops in earlier experiments were addressed by design and material refinements. We continue to focus on developing effective anticoagulation management in the lamb model as well as on further evaluating and demonstrating pump biocompatibility.

A large effective area multi-core fiber with an optimized cladding thickness.

The cladding thickness of trench-assisted multi-core fibers was theoretically and experimentally investigated in terms of excess losses of outer cores. No significant micro-bending loss increase was observed on multi-core fibers with the cladding thickness of about 30 µm. The tolerance for the micro-bending loss of a multi-core fiber is larger than that of the single core fiber. However, the cladding thickness will be limited by the occurrence of the excess loss on outer cores. The reduction of cladding thickness is probably limited around 40 µm in terms of the excess loss. The multi-core fiber with an effective area of 110 µm(2) at 1.55 µm and 181-µm cladding diameter was realized without any excess loss.

Large-effective-area ten-core fiber with cladding diameter of about 200 µm.

A multicore fiber with two-pitch layout is proposed to overcome the trade-off between core number and a cladding diameter of a standard hexagonal layout with a single-core pitch. A fabricated ten-core fiber simultaneously realizes effective area of about 120 µm(2) at 1550 nm, small crosstalk, and cladding diameter of 204 µm. The crosstalk between the center core and outer cores is about 30 dB smaller than that between outer cores. The small crosstalk of the center core would help to keep the transmission quality of the center core at the same level as that of the outer cores.

Novel implantable device to detect cardiac allograft rejection.

BACKGROUND: Allograft rejection remains the nemesis of solid organ transplantation. Soul Mate is a novel implantable wireless data transmission system that analyzes 9 intramyocardial electrogram parameters recorded from 4 or 6 configurations of 2 or 3 epicardial leads to detect allograft rejection. This study determined the ability of the Soul Mate to detect early rejection of transplanted hearts. METHODS AND RESULTS: Five dogs underwent heterotopic cervical heart transplantation and simultaneous implantation of the Soul Mate's Cardiac Rejection Monitoring Device. Dogs were initially immunosuppressed, but subsequent drug discontinuation allowed allograft rejection to appear. Allograft biopsies were performed at regular intervals to determine rejection grade, which was compared to a calculated rejection score determined as percent change from baseline of values for each intramyocardial electrogram. There was significant correlation between the biopsy results and the evolution of 5 parameters. The strongest correlation (r=0.939; P<0.001) was obtained using the "general median" parameter from 4 configurations, assessed 1 day before the biopsy, with a sensitivity of 85.7% and a specificity of 100% compared to the myocardial biopsy results. CONCLUSIONS: The Soul Mate allograft rejection monitoring system accurately detected transplanted heart rejection in a canine model noninvasively with continuous sampling. This proof-of-concept study suggests that the Soul Mate could be used to more intensely and more frequently monitor cardiac allografts for rejection.

In vivo biocompatibility evaluation of a new resilient, hard-carbon, thin-film coating for ventricular assist devices.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

Mitral annular remodeling to treat functional mitral regurgitation: a pilot acute study in a canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility and efficacy of the injection of a nonabsorbable substance into the base of the left ventricle (LV) to treat functional mitral regurgitation (MR). METHODS: Tyramine-based hyaluronan hydrogel was injected into the base of the LV of the beating heart in a canine model of rapid ventricular pacing-induced functional MR (n = 4). The severity of MR was evaluated by epicardial echocardiography before and after hydrogel injection. RESULTS: The injection improved MR grade from 3.4 +/- 0.8 to 1.3 +/- 0.5 (P = .006) without inducing hemodynamic instability or any evidence of myocardial ischemia. We noted significant decreases in the septal-lateral dimension at the mitral annulus (3.4 +/- 0.4 cm to 2.9 +/- 0.3 cm; P = .039) and MR volume (20.6 +/- 7.3 mm3 to 5.2 +/- 2.2 mm3; P = .044). CONCLUSIONS: A novel treatment consisting of hydrogel injection into the base of the LV between the 2 papillary muscles was found to be feasible and effective for reducing functional MR in a canine model.

The PediPump: a versatile, implantable pediatric ventricular assist device--update IV.

Cleveland Clinic's PediPump (Cleveland, OH, USA) is a ventricular assist device designed for the support of pediatric patients. The PediPump is a mixed-flow ventricular assist device with a magnetically suspended impeller measuring 10.5 mm in diameter by 64.5 mm in length. Progress and achievements for the PediPump program are considered according to the development project's three primary objectives: Basic engineering: along with size reductions, substantial design improvements have been incorporated in each design iteration including the motor, magnetic bearings, axial touch points, and heat transfer path; Anatomic modeling and device fitting studies: Techniques based on computed tomography and magnetic resonance imaging have been developed to create three-dimensional anatomic-modeling and device-fitting tools to facilitate device implantation and to assist in preoperative planning. For in vivo testing, to date, six acute (6-h duration) and nine chronic (30-day target duration) implantations have been performed in sheep; the implantation of the PediPump appears to be relatively easy with excellent hemodynamic performance and minimal hemolysis during support. Cleveland Clinic's PediPump program supported by the National Heart, Lung and Blood Institute's Pediatric Circulatory Support Program has led to the development of a pediatric ventricular assist device that has satisfactory performance in preclinical evaluation and appears to be ready to support a program of clinical testing.

The bite-raised condition in aged SAMP8 mice reduces the expression of glucocorticoid receptors in the dorsal and ventral hippocampus.

In the present study, we examined whether the effects induced by the bite-raised condition on glucocorticoid receptor (GR) expression differ between the dorsal and ventral hippocampus in SAMP8 mice. In the bite-raised condition, the number of GR-immunoreactive cells was significantly decreased in both the dorsal and ventral CA1 and dentate gyrus (DG) subfields of the hippocampus compared to control mice, as revealed by immunohistochemical analysis. The decrease in the number of GR-immunoreactive cells tended to be greater in the dorsal hippocampus than in the ventral hippocampus. Only in the DG subfield was there a significant difference in the number of GR-immunoreactive cells between the dorsal and ventral hippocampus. These findings suggest that in aged SAMP8 mice, the bite-raised condition decreases the number of GR-immunoreactive cells in both the dorsal and ventral hippocampus.

The bite-raised condition enhances the aging process in the dorsal and ventral hippocampus.

The bite raised condition decreases the number of neurons and increases the amount of glial fibrillary acidic protein in the hippocampus of aged SAMP8 mice. In the present study, we examined whether these effects differ between the dorsal and ventral hippocampus. In bite-raised SAMP8 mice, the number of neurons was significantly lower in the hippocampal CA1 and dentate gyrus (DG) subfields compared to control mice. In the bite raised condition, the number of neurons was significantly lower in both the dorsal and ventral CA3 subfields, and the number of glial fibrillary acidic protein-labeled astrocytes was increased in the CA1, CA3, and DG subfields, compared to control mice. These data suggest that in aged SAMP8 mice, the bite-raised condition enhanced aging processes in both the dorsal and ventral hippocampus.

Acute Swine Model for Assessing Biocompatibility of Biomedical Interface Materials.

We established an acute animal model for early, straightforward, and reproducible assessment of a biocompatible material interface. Bilateral femoral artery-to-vein shunts were created in 12 pigs: two tubes per shunt, the left two coated and the right two uncoated. We evaluated two groups: uncontrolled flow (UF; shunt flow unregulated) and controlled flow (CF; shunt flow ∼50 mL/min). For each case on each side, two shunts were evaluated: one for 1 h and the other for 3 h. Arterial blood gas and complete blood count were recorded at baseline, 1, and 3 h. Mean shunt flows were 532 ± 88 mL/min UF and 52 ± 8 mL/min CF. Differences in flow were much smaller in CF (0.5 mL/min; 1% of mean flow) than UF (24.8 mL/min; 5% of mean flow). In UF, significant changes occurred: in pH, from start of shunting through 1 h; in pO2 and pCO2, from start through 3 h. This swine model using bilateral femoral shunts with controlled blood flow provides a reliable, reproducible, easily implemented method by which to evaluate biocompatibility of device coatings at an early stage of investigation.

Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice.

To evaluate the mechanism underlying impaired cognitive function due to occlusal disharmony, we examined the effect of the bite-raised condition on spatial performance and hippocampal expression of glucocorticoid receptors (GR) and glucocorticoid receptor messenger ribonucleic acid (GRmRNA) using behavioral, immunohistochemical, and in situ hybridization techniques. Learning ability in the water maze test was significantly impaired in aged bite-raised mice compared with age-matched control mice. There was no difference between control and bite-raised young and middle-aged mice. Also, immunohistochemical and in situ hybridization analysis showed that the bite-raised condition enhanced the age-related decrease in GR and GRmRNA expression in the hippocampus. In particular, GR and GRmRNA expressions were significantly decreased in aged bite-raised mice compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice decreases GR and GRmRNA, which impairs the hypothalamic-pituitary-adrenal feedback inhibition, thereby leading to memory deficits.

Duration-dependent effects of the bite-raised condition on hippocampal function in SAMP8 mice.

We evaluated the effect of the duration of occlusal disharmony induced chronic stress on hippocampal function by examining spatial memory in the Morris water maze and on the number of hippocampal neurons in aged senescence-accelerated prone (SAMP8) mice. The bite of SAMP8 mice was raised 0.1 mm using dental adhesive. Groups of mice were tested in the Morris water maze 8, 11, or 22 d after raising the bite. The results indicated that the longer the duration of the bite-raised condition, the greater the impairment in spatial learning ability and the greater the decrease in the number of neurons in the hippocampal CA3 subfield. Thus, behavioral and morphologic deficits induced by the bite-raised condition in aged SAMP8 mice are influenced by the duration of the occlusal disharmony.

Left atrial appendage occlusion: pilot study of a fourth-generation, minimally invasive device.

OBJECTIVE: Exclusion of the left atrial appendage is proposed to reduce the risk of stroke in patients with atrial fibrillation. The aim of this study was to evaluate the feasibility and efficacy of a fourth-generation atrial exclusion device developed for minimally invasive applications. METHODS: The novel atrial exclusion device consists of two polymer beams and two elastomeric bands that connect the two beams at either end. Fifteen mongrel dogs were implanted with the device at the base of the left atrial appendage through a median sternotomy and were evaluated at 30 (n = 7), 90 (n = 6), and 180 (n = 2) days after implantation by epicardial echocardiography, left atrial and coronary angiography, gross pathology, and histology. RESULTS: Left atrial appendage exclusion was completed without hemodynamic instability. Coronary angiography revealed that the left circumflex artery was patent in all cases. A new endothelial tissue layer developed, as expected, on the occluded orifice of the left atrium. CONCLUSIONS: This novel atrial exclusion device achieved easy, reliable, and safe exclusion of the left atrial appendage, with favorable histological results in a canine model for up to 6 months. Clinical application could provide a new therapeutic option for reducing the risk of stroke in patients with atrial fibrillation.

Direct endoscopy-guided mitral valve repair in the beating heart: an acute animal study.

OBJECTIVE: : The purpose of this study was to develop a new method for minimally invasive mitral valve repair under direct endoscopic visualization in the beating heart. METHODS: : Fiberoptic cardioscopy of the left heart was conducted in 12 calves. Systemic perfusion was maintained by cardiopulmonary bypass through a median sternotomy. A clear solution (Ringer's lactate) was temporarily administered via the pulmonary artery to flush out the pulmonary vasculature, and additional perfusion of the left heart chambers enhanced visualization of the intracardiac anatomy. The endoscope, with an open-ended transparent flexible outer sheath, was inserted through the left ventricular apex, and an endoscopic clip was used for edge-to-edge mitral valve repair. Hemodilution was avoided by the drainage of irrigation fluid via a left ventricular cannula. RESULTS: : Direct endoscopic visualization of the mitral valve in an in vivo beating heart was obtained clearly, avoiding systemic hemodilution. In the last experiment, edge-to-edge repair using an endoscopic clip was successfully performed. Use of an effective intracardiac irrigation method was important for successful image acquisition and achievement of repair procedures. CONCLUSIONS: : This acute animal study showed the technical feasibility of beating-heart mitral valve surgery under direct endoscopic imaging. Although this study was performed under open-chest conditions, our successful experiment is a first step toward closed-chest intracardiac surgery with direct endoscopic visualization.

Superior chest drainage with an active tube clearance system: evaluation of a downsized chest tube.

PURPOSE: We developed a small-diameter (20-French [Fr]) chest drainage system that incorporates an active tube clearance (ATC) system, and we evaluated its efficacy in an acute hemothorax model. DESCRIPTION: The ATC system includes an internal guidewire that can be advanced into the lumen of the chest tube to keep the tube from clogging. In six pigs, a 20-Fr ATC tube was placed on one side and a 32-Fr standard tube on the other, and 120 mL of fresh blood was infused into each pleural space every 15 minutes for a total of 840 mL. EVALUATION: The amount of drainage for 2 hours with a 20-Fr ATC tube was significantly greater than that with the 32-Fr standard tube (525 ± 179 mL vs 183 ± 85 mL; p = 0.0032). CONCLUSIONS: This is the first time a smaller diameter tube has been shown to have better drainage in the setting of acute bleeding compared with larger diameter tubes.

In vivo evaluation of a new surfactant polymer coating mimicking the glycocalyx of endothelial cells.

The purpose of this study was to demonstrate that a proprietary surfactant polymer (SP) coating does not adversely affect the hemodynamic performance of cardiopulmonary bypass (CPB) or gas exchange in oxygenators. The new coating was applied to a CPB circuit including cannulae, reservoir, oxygenator, and blood pump implanted into 12 pigs, divided into groups with either coated or noncoated pumps. CPB flow was maintained at a fixed level of approximately 2.4 L/min for 6 hours with full heparinization. Hemodynamic data and pump performance were recorded every hour, and blood samples were taken every 2 hours. After sacrifice, the CPB circuit and major organs were macroscopically examined. There was no significant difference in the oxygen transfer rate between the two groups. The coating did not adversely affect oxygenator inlet or outlet pressures. There was no significant difference between the two groups in microthrombi seen in the oxygenators. No thromboemboli were noted in the major organs on gross or histologic examination. In conclusion, this new SP coating did not decrease gas exchange performance, and its biocompatibility evaluations revealed no differences between coated and noncoated groups under aggressive heparin use.

Circulating blood volumes: a review of measurement techniques and a meta-analysis in children.

The accurate determination of circulating blood volume (CBV) in children has many clinical applications. The purposes of this article were to review currently available CBV measurement techniques and perform a meta-analysis using values from many small-scale studies that calculated CBV values for normal healthy children. A literature review demonstrated numerous methods by which to determine CBV. However, these methods necessitate repetitive blood sampling, require the introduction of foreign substances into the bloodstream, or address the uncertainty of substance distribution and clearance. Many small-scale studies have calculated CBV values for normal healthy children, and we performed a meta-analysis using these values. Age groups were defined, and within each group, means +/- 1 and 2 standard deviations were compared. A pooled estimate of mean blood volume and a 95% confidence interval was calculated after Q-statistics calculations indicated that the groups were homogeneous. Mean values showed agreement with typically accepted normal values. A large-scale study should be repeated when a gold standard for CBV measurements is developed.

Novel epicardial off-pump device for mitral regurgitation: acute evaluation.

OBJECTIVE: This study evaluates the ability of a novel epicardial annuloplasty device Mitral Touch (MAQUET Cardiovascular LLC, San Jose, CA, USA) to reduce functional mitral regurgitation (MR) in a rapid ventricular pacing-induced dilated cardiomyopathy model in dogs. METHODS: A median sternotomy was performed in 13 dogs after MR induction by rapid ventricular pacing (230 beats/min for an average of 35.6 + or - 12.8 days). Two-dimensional epicardial echocardiographic and haemodynamic measurements were performed to evaluate the baseline MR grade, the septal-lateral (S-L) dimension of the mitral annulus, mitral valve (MV) geometry and left ventricular function. The Mitral Touch was implanted by sliding the anterior arm onto the floor of the transverse sinus and positioning the posterior arm just apical to the atrioventricular groove on the left ventricular posterolateral wall. The 24-mm-long device was implanted in eight dogs, the 27-mm-long device in four and the 30-mm standard length device in one. MR grade, S-L dimension and haemodynamics data acquisition were immediately rechecked after device implantation. RESULTS: All implantations, which took only approximately 30s to deploy, were performed on beating hearts without cardiopulmonary bypass. In one early case, after extended manipulation with undersized devices, an atrial laceration was created and bleeding occurred. Design changes were made to eliminate this complication. The MR grade was significantly (p=0.003) reduced from 3.1 + or - 1.1 at baseline to 1.4 + or - 0.8 after device implantation. The S-L dimension at end of systole was also significantly (p=0.001) reduced from 2.7 + or - 0.4 cm at baseline to 2.3 + or - 0.3 cm after device implantation (% reduction: 15.1 + or - 10.6%). The mitral valve coaptation length was significantly (p=0.0001) increased from 0.36 + or - 0.11 cm to 0.50 + or - 0.08 cm, and the mitral valve tethering area was significantly (p=0.0003) decreased from 1.36 + or - 0.38 cm(2) to 0.81 + or - 0.29 cm(2) after Mitral Touch implantation. CONCLUSIONS: This new epicardial device was effective in significantly reducing MR and S-L dimensions acutely on the beating heart without requiring the use of cardiopulmonary bypass. Further studies are necessary to confirm the long-term maintenance of MR and S-L reductions.

Improved drainage with active chest tube clearance.

This study was performed to evaluate the efficacy of a novel chest drainage system. This system employs guide wire-based active chest tube clearance to improve drainage and maintain patency. A 32 Fr chest tube was inserted into pleural cavities of five pigs. On the left, a tube was connected to the chest canister, and on the right, the new system was inserted between the chest tube and chest canister. Acute bleeding was mimicked by periodic infusion of blood. The amount of blood drained from each chest cavity was recorded every 15 min for 2 h. After completion of the procedure, all residual blood and clots in each chest cavity were assessed. The new system remained widely patent, and the amount of drainage achieved with this system (670+/-105 ml) was significantly (P=0.01) higher than that with the standard tube (239+/-131 ml). The amount of retained pleural blood and clots with this system (150+/-107 ml) was significantly (P=0.04) lower than that with the standard tube (571+/-248 ml). In conclusion, a novel chest drainage system with active tube clearance significantly improved drainage without tube manipulations.

Acute feasibility study of a novel device for the treatment of mitral regurgitation in a normal canine model.

OBJECTIVE: : The purpose of this study was to evaluate the implantability of a novel epicardial mitral annuloplasty device and its ability to reduce the septal-lateral (S-L) dimension of the mitral annulus. METHODS: : The devices were implanted on the beating heart in 2 healthy dogs (the 24-mm long device in dog A and the 27-mm and 24-mm standard devices in dog B) by sliding the anterior arm onto the floor of the transverse sinus and positioning the posterior arm just apical to the atrioventricular groove on the left ventricular posterolateral wall. The devices were secured with titanium helical tacks driven through the device into the ventricular wall. Two-dimensional epicardial echocardiograms were performed before and after device implantation to evaluate the degree of mitral regurgitation (MR) and the S-L dimension. RESULTS: : Device implantation was uneventful, taking only ∼30 seconds to deploy. MR (1+) in both dogs at baseline was reduced to zero after implant. The reductions in S-L dimension in systole for the 24-mm device were 7.5% in dog A and 30.5% in dog B. For the 27-mm device in dog B, S-L reduction in systole was 29.9%. The leaflet coaptation length was increased in both cases. CONCLUSIONS: : The new device was effective in reducing S-L dimension and 1+ MR without requiring the use of cardiopulmonary bypass. We are currently evaluating this device for the treatment of MR in a rapid-pacing canine heart failure model.