Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung.

The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.

Use of a low-resistance compliant thoracic artificial lung in the pulmonary artery to pulmonary artery configuration.

BACKGROUND: Thoracic artificial lungs have been proposed as a bridge to transplant in patients with end-stage lung disease. Systemic embolic complications can occur after thoracic artificial lung attachment in the pulmonary artery to left atrium configuration. Therefore, we evaluated the function of a compliant thoracic artificial lung attached via the proximal pulmonary artery to distal main pulmonary artery configuration. METHODS: The compliant thoracic artificial lung was attached to 5 sheep (63 ± 0.9 kg) in the proximal pulmonary artery to distal main pulmonary artery configuration. Device function and animal hemodynamics were assessed at baseline and with approximately 60%, 75%, and 90% of cardiac output diverted to the compliant thoracic artificial lung. At each condition, dobutamine (0 and 5 µg·kg(-1)·min(-1)) was used to simulate rest and exercise conditions. RESULTS: At rest, cardiac output decreased from 6.20 ± 0.53 L/min at baseline to 5.40 ± 0.43, 4.66 ± 0.31, and 4.05 ± 0.27 L/min with 60%, 75%, and 90% of cardiac output to the compliant thoracic artificial lung, respectively (P < .01 for each flow diversion vs baseline). During exercise, cardiac output decreased from 7.85 ± 0.70 L/min at baseline to 7.46 ± 0.55, 6.93 ± 0.51, and 5.96 ± 0.44 L/min (P = .82, P = .19, and P < .01 with respect to baseline) with 60%, 75%, and 90% of cardiac output to the compliant thoracic artificial lung, respectively. The artificial lung resistance averaged 0.46 ± 0.02 and did not vary significantly with blood flow rate. CONCLUSIONS: Use of a compliant thoracic artificial lung may be feasible in the proximal pulmonary artery to distal main pulmonary artery setting if its blood flow is held at less than 75% of cardiac output. To ensure a decrease in cardiac output of less than 10%, a blood flow rate less than 60% of cardiac output is advised.

Thoracic artificial lung impedance studies using computational fluid dynamics and in vitro models.

Current thoracic artificial lungs (TALs) possess blood flow impedances greater than the natural lungs, resulting in abnormal pulmonary hemodynamics when implanted. This study sought to reduce TAL impedance using computational fluid dynamics (CFD). CFD was performed on TAL models with inlet and outlet expansion and contraction angles, θ, of 15°, 45°, and 90°. Pulsatile blood flow was simulated for flow rates of 2-6 L/min, heart rates of 80 and 100 beats/min, and inlet pulsatilities of 3.75 and 2. Pressure and flow data were used to calculate the zeroth and first harmonic impedance moduli, Z(0) and Z(1), respectively. The 45° and 90° models were also tested in vitro under similar conditions. CFD results indicate Z(0) increases as stroke volume and θ increase. At 4 L/min, 100 beats/min, and a pulsatility of 3.75, Z(0) was 0.47, 0.61, and 0.79 mmHg/(L/min) for the 15°, 45°, and 90° devices, respectively. Velocity band and vector plots also indicate better flow patterns in the 45° device. At the same conditions, in vitro Z (0) were 0.69 ± 0.13 and 0.79 ± 0.10 mmHg/(L/min), respectively, for the 45° and 90° models. These Z(0) are 65% smaller than previous TAL designs. In vitro, Z(1) increased with flow rate but was small and unlikely to significantly affect hemodynamics. The optimal design for flow patterns and low impedance was the 45° model.

In-parallel attachment of a low-resistance compliant thoracic artificial lung under rest and simulated exercise.

BACKGROUND: Previous thoracic artificial lungs (TALs) had blood flow impedance greater than that of the natural lungs, which could cause abnormal pulmonary hemodynamics. New compliant TALs (cTALs), however, have an impedance lower than that of the natural lung. METHODS: In this study, a cTAL of new design was attached between the pulmonary artery (PA) and the left atrium (LA) in 5 sheep (60.2 ± 1.9 kg). A distal PA band was placed to control the percentage of cardiac output (CO) routed to the cTAL. Rest and exercise conditions were simulated using a continuous dobutamine infusion of 0 and 5 µg/kg/min, respectively. At each dose, a hemodynamic data set was acquired at baseline (no flow to the cTAL), and 60%, 75%, and 90% of CO was shunted to the cTAL. RESULTS: Device resistance did not vary with blood flow rate, averaging 0.51 ± 0.03 mm Hg/(L/min). Under all conditions, CO was not significantly different from baseline. Pulmonary system impedance increased above baseline only with 5 µg/kg/min of dobutamine and 90% of CO diverted to the cTAL. CONCLUSIONS: Results indicated minimal changes in pulmonary hemodynamics during PA-LA cTAL attachment for high device flows under rest and exercise conditions.

Design and in vitro assessment of an improved, low-resistance compliant thoracic artificial lung.

Current thoracic artificial lungs (TALs) have blood flow impedances greater than the natural lungs, which can result in abnormal pulmonary hemodynamics. This study investigated the impedance and gas transfer performance of a compliant TAL (cTAL). Fluid-structure interaction analysis was performed using ADINA (ADINA R&D Inc., Watertown, MA) to examine the effect of the inlet and outlet expansion angle, θ, on device impedance and blood flow patterns. Based on the results, the θ = 45° model was chosen for prototyping and in vitro testing. Glycerol was pumped through this cTAL at 2, 4, and 6 L/min at 80 and 100 beats/min, and the zeroth and first harmonic impedance moduli, Z(0) and Z(1), were calculated. Gas transfer testing was conducted at blood flow rates of 3, 5, and 7 L/min. Fluid-structure interaction results indicated that the 45° model had an ideal combination of low impedance and even blood flow patterns and was thus chosen for prototyping. In vitro, Z(0) = 0.53 ± 0.06 mm Hg/(L/min) and Z(1) = 0.86 ± 0.08 mm Hg/(L/min) at 4 L/min and 100 beats/min. Outlet PO(2) and SO(2) values were above 200 mm Hg and 99.5%, respectively, at each flow rate. Thus, the cTAL had lower impedance than hard shell TALs and excellent gas transfer.

Performance of a MedArray silicone hollow fiber oxygenator.

A silicone hollow fiber oxygenator was evaluated to characterize gas transfer and biocompatibility. The device's fiber bundle was composed of MedArray's silicone hollow fibers with a 320 microm outside diameter, a 50 microm wall thickness, a surface area of 0.45 m, and a 0.49 void fraction. An in vitro gas exchange study was performed comparing the MedArray device (n = 9) with the Medtronic 0600 oxygenator (n = 6) using Association for the Advancement of Medical Instrumentation standards and blood flow rates of 0.5-1.75 L/min, and an oxygen to blood flow ratio of two. Biocompatibility and resistance studies were performed in vivo using a swine venovenous extracorporeal membrane oxygenation model (MedArray n = 5, Medtronic n = 5). Average O(2) transfer at 1 L/min was 86 ml/min/m in the MedArray device and 101.1 ml/min/m in the Medtronic device. At 0.5 L/min the MedArray and Medtronic device average resistance was 15.5 and 148.5 mm Hg/(L/min), respectively. Both devices had similar platelet consumption and hemolysis. Results indicate that the MedArray device has lower O(2) transfer efficiency, similar biocompatibility, and lower resistance than the Medtronic 0600 oxygenator. Optimization of the MedArray fiber bundle and housing design is necessary to improve O(2) transfer efficiency while maintaining lower device resistance than the Medtronic oxygenator.