George P. Noon

Decreased expression of tumor necrosis factor-α in failing human myocardium after mechanical circulatory support: A potential mechanism for cardiac recovery

BACKGROUNDnAn increasing number of observations in patients with end-stage heart failure suggest that chronic ventricular unloading by mechanical circulatory support may lead to recovery of cardiac function. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine capable of producing pulmonary edema, dilated cardiomyopathy, and death. TNF-alpha is produced in the myocardium in response to volume overload; however, the effects of normalizing ventricular loading conditions on myocardial TNF-alpha expression are not known. We hypothesize that chronic ventricular unloading by the placement of a left ventricular assist device (LVAD) may eliminate the stress responsible for persistent TNF-alpha expression in human failing myocardium.nnnMETHODS AND RESULTSnMyocardial tissue was obtained from normal hearts and from paired samples of 8 patients with nonischemic end-stage cardiomyopathy at the time of LVAD implantation and removal. Tissue sections were stained for TNF-alpha, and quantitative analysis of the stained area was performed. We found that TNF-alpha content decreased significantly after LVAD support. Furthermore, the magnitude of the changes did not correlate with the length of LVAD support, although greater reductions in myocardial TNF-alpha content were found in patients who were successfully weaned off the LVAD who did not require transplantation.nnnCONCLUSIONSnThese data show for the first time that chronic mechanical circulatory assistance decreases TNF-alpha content in failing myocardium; furthermore, we suggest that the magnitude of the change may predict which patients will recover cardiac function.

Comparison of hemodynamics in the ascending aorta between pulsatile and continuous flow left ventricular assist devices using computational fluid dynamics based on computed tomography images.

This study aims to investigate differences in hemodynamic conditions in the thoracic aorta for pulsatile and continuous-flow left ventricular assist devices (LVADs) using computational fluid dynamics (CFD). Patient-specific models were reconstructed from three patients with continuous-flow LVAD (HeartMate II, Thoratec Corporation) and three patients with biventricular assist devices (Excor, Berlin Heart) where only the aortic part was included in the simulations. CFD simulations were performed with constant inflow for the continuous-flow LVADs and time-varying inflow for the pulsatile devices. Differences in flow patterns, wall shear stress (WSS), and dynamic pressure in the ascending aorta were compared for both cases. Retrograde flow patterns were observed in all cases proximal to the location of the outflow cannula anastomosis site. On average, dynamic pressures derived from the retrograde flow velocities were higher in the continuous-flow group with large variations dependent on the angle of the cannula anastomosis relative to the ascending aorta (continuous group: 0.14u2009±u20090.2u2009mmu2009Hg, pulsatile group: 0.013u2009±u20090.008u2009mmu2009Hg). Elevated WSS contralaterally to the anastomosis site was observed in three of the six models with higher values for the continuous cases. Lower WSS and reduced pressure in the ascending aorta, both favorable hemodynamic conditions, were found in pulsatile versus continuous-flow LVADs by means of CFD. These findings indicate, along with clinical observations reported by others, the superior performance of pulsatile LVADs.

Ex vivo evaluation of the NASA/DeBakey axial flow ventricular assist device. Results of a 2 week screening test.

The authors investigated the antithombogenicity of the NASA/DeBakey axial flow ventricular assist device in an ex vivo calf model. The device is 3 inches in length and 1 inch in largest diameter. The pump weighs 53 g and displaces 15 ml. The unit consists of three major components: a flow straightener, a spinning inducer/impeller, and a diffuser. The impeller has rod shaped permanent magnets embedded within the six blades and is activated magnetically by a motor stator that is positioned outside the flow tube. Previous 2 day screening tests demonstrated an antithrombogenic configuration in short-term implantation. Based on the results of these 2 day screening tests, five pumps with the best configuration were implanted into a calf for 2 weeks for anti thrombogenicity confirmation. Pumps were implanted paracorporeally, and heparin was used to maintain activated clotting time to approximately 250 sec. Each pump was changed every 2 weeks as planned. During the experiment, all pumps demonstrated stable pumping. The required electric power was 7 to 8 watts and pump flow was maintained at 4 L/min. The calf was in excellent condition. Liver and renal function were maintained, plasma free hemoglobin was kept at less than 4 mg/dl (3.3 +/- 0.3 mg/dl), and lactate dehydrogenase was 1043 +/- 36 units/L. In this experimental series, all five pumps passed the 2 week implantation. Two week ex vivo test results indicated very slight thrombus in the hub areas of some pumps. For the next phase of the implantation study, minor design optimization is necessary to completely eliminate thrombus formation. According to our step by step approach, the in vivo test aiming for long-term implantation is ongoing.

Integration of the computational fluid dynamics technique with MRI in aortic dissections

Short‐term and long‐term prognosis and their determining factors of Type III/Stanford B aortic dissections (TB‐AD), which separate the aorta distal at the origin of the subclavian artery into a true lumen and false lumen, have been elusive: One quarter of patients thought to be treated successfully, either by medical or by surgical means, do not survive 3 years. Unfavorable hemodynamic conditions are believed to lead to false lumen pressure increases and complications. A better characterization of TB‐AD hemodynamics may therefore impact therapeutic decision making and improve outcome. The large variations in TB‐AD morphology and hemodynamics favor a patient‐specific approach. Magnetic resonance imaging with its capability to provide high‐resolution structural images of the lumen and aortic wall and also to quantify aortic flow and kinetics of an exogenous tracer is a promising clinical modality for developing a deeper understanding of TB‐AD hemodynamics in an individual patient. With the information obtained with magnetic resonance imaging, computational fluid dynamics simulations can be performed to augment the image information. Here, an overview of the interplay of magnetic resonance imaging and computational fluid dynamics techniques is given illustrating the synergy of these two approaches toward a comprehensive morphological and hemodynamic characterization of TB‐AD. Magn Reson Med, 2013.

Magnetically guided recellularization of decellularized stented porcine pericardium-derived aortic valve for TAVI.

Application of somatic stem cells for growth, proliferation, and differentiation in a three-dimensional pattern is an important aspect in tissue engineering. Here, we report on our bioreactor, which we applied for magnetically guided recellularization of nitinol-stented valve. Human-derived unrestricted somatic stem cells were cultured in medium in our pulsatile dynamic bioreactor for 4–6 days. Stented valves were prepared by decellularization of porcine pericardium and construction of stented tissue-engineered valves (n = 8). A magnetic field was created around the bioreactor to prevent the loss of cells. In the control group, no magnetic device was used (n = 4). Morphological characterization was assessed by immunohistochemical staining of paraffin sections and electron microscopy. The bioreactor enabled the preservation of physiologic culture conditions with aerobic cell metabolism and physiological pH values. Histological analysis showed homogeneous seeding of the pericardium with progenitor cells in the recellularized samples, whereas no cell seeding could be observed in the nonmagnetic group. Our magnetically guided multifunctional bioreactor allows for an efficient three-dimensional culturing of somatic stem cells on decellularized organ-specific matrix.

The Baylor-ABI Electromechanical Total Artificial Heart: Accelerated Endurance Testing

To test the durability of each part or assembled component of the Baylor-ABI total artificial heart (TAH), the authors performed an endurance test under severe conditions. The TAH was immersed in a saline bath at 42 degrees C, which is 4-5 degrees C higher than normal body temperature. This is an accelerated endurance test because of the elevated temperatures. In this accelerated endurance test loop, the 42 degrees C heated saline was circulated not only in the pump but also outside the pump. During pumping, temperatures of the motor and outside surface of the centerpiece were continuously measured. This testing showed that during almost 4 months of pumping no electromechanical troubles were observed. Both inside (motor) and outside temperatures were stable and the differences in both temperatures were only 3-4 degrees C, demonstrating that heat generation is not a problem. The voltage and current required in this system remained constant, indicating stable and reliable performance. Based on these results, this pump is expected to run continuously over a long duration in a normal physiologic environment. This accelerated endurance test system is very suitable for estimating the influence of heat generation by the actuator of blood pumps. It is also quite useful in validating the durability of various cardiac prosthesis.

Phase 1 Ex Vivo Studies of the Baylor/NASA Axial Flow Ventricular Assist Device

The Baylor/NASA ventricular assist device (VAD) is a small, electrically driven, valveless axial flow pump that is implantable inside the chest cavity. It is intended to assist a diseased heart. In the phase 1 study of this pump development program, the 2-day pump is intended to produce an assist device for cardiopulmonary bypass (CPB) application. The main focus of this phase of the program was to develop a pump which produced minimum blood trauma. Antithrombogenic features are planned to be incorporated into the phase 2 pump. In this phase 1 study, eight pumps were implanted paracorporeally in two calves as LVADs to assess hemolysis, pump performance, efficiency, and stability, the goal for this study being a 2-day implantation. The pump running times ranged from 18 to 203 (78.1 ± 23.7; mean ± SE) h. Plasma free hemoglobin levels were below 13.7 mg/di, except for one case complicated by inflow cannula obstruction due to pannus formation. Pump speed was maintained between 10100 and 11400rpm. Pump output ranged from 3.6 to 5.11/min. The electrical power required by the system ranged from 10.5 to 12.8W. No detectable organ dysfunction was noted and postmortem evaluations demonstrated no pump-related adverse effects in any of the calves. Thrombus deposition was observed mainly at the hub area and flow straightener. For the next series of experiments (phase 2), the thrombogenic regions in these subacute experiments should be eliminated.