Flow through the artificial lung in the absence of compliance generated Z0 and Z1 of 1.31 ± 0.01 and 4.61 ± 0.02 Woods Units, respectively. Addition of the compliance chamber without compression slightly increased resistance for all chamber volumes (1.63 ± 0.02, 1.55 ± 0.03, 1.67 ± 0.003, and 1.70 ± 0.10 for reservoir volumes of 50, 100, 250, and 500 ml, respectively;p < 0.05), but had no effect on Z1.
External pneumatic compression of the compliance chamber reduced Z1 for all chamber volumes, with the lowest Z1 occurring while using the 250 ml reservoir compressed to 12 mm Hg (Figure 6). Compression beyond 12 mm Hg elevated Z1. Pneumatic compression also reduced Z0 at 12 mm Hg for all chamber volumes (Figure 7). Again, compression beyond 12 mm Hg resulted in Z0 elevation. This effect was minimized with the use of the stented compliance reservoir. BFP was reduced with external pneumatic compression of the compliance chamber. Minimum pulsatility was achieved with the 250 ml compliance reservoir when compressed at 14 mm Hg (Figure 8).
Numerous laboratories are developing artificial lungs using a variety of designs and applications, all with the eventual goal of producing a viable bridge or alternative to lung transplantation. Extracorporeal life support (ECMO) has been successfully used as a short-term treatment of acute respiratory failure, serving as a bridge to recovery. 9 However, the practical duration of ECMO is limited by the complexity, cost, and inevitable complications that arise with prolonged treatment. In addition, ECMO in its current form can only be provided in the intensive care unit setting, with minute-to-minute direct observation by trained personnel. We believe that the complexity associated with ECMO can be attributed in large part to the mechanical pump required to generate blood flow and the necessary length of conduit tubing. An oxygenator with low resistance to blood flow can be perfused by the native cardiac output, thus obviating the need for a mechanical pump. This design allows for extracorporeal gas exchange but avoids the cellular blood element trauma associated with blood pumps and potentially minimizes cost. In addition, the simplicity of this design appears practical for use as a long-term ambulatory treatment.
Several potential applications can be used incorporating venous delivery through an artificial lung. A theoretical lumped-parameter model has previously described the impact in terms of cardiac load for several of these approaches. 10 When the inflow blood from the right ventricle is returned into the left atrium, flow can either be exclusively through the artificial lung, as in pulmonary replacement, or competitive with the native pulmonary circulation, providing partial respiratory support. The parallel support approach will not increase right ventricular load, as the compliance of the pulmonary vascular bed will remain in place. In fact, this application can significantly reduce cardiac load in the setting of severe pulmonary hypertension and right ventricular failure, as is frequently present in patients with end-stage lung disease. 5 However, this application cannot satisfy all of the gas exchange requirements as some pulmonary blood flow continues, potentially leaving some patients hypoxic. In addition, patients such as those with cystic fibrosis may be at greater risk of infectious complications by leaving the pyogenic native lungs in place. Total support in the form of artificial pulmonary replacement may be more appropriate in these cases. However, as demonstrated in the previous lumped-parameter model, this configuration can drastically alter cardiac load, potentially resulting in right ventricular failure.
The bench-top simulation used in this study is a simplified model of the right-sided circulation, with a VAD producing physiologic pulsatile flow and an elevated reservoir generating a hydrostatic pressure to reproduce relatively constant left atrial pressure. Several limitations in this bench-top system can be elucidated, such as the fixed pump rate, stroke volume, and the use of water in the system rather than blood. Further studies accounting for these limitations are undoubtedly necessary. However, the ease of preparation and its reproducibility make this simulation a satisfactory initial assessment of the cardiac load produced by an artificial lung with a prototype compliance chamber.
The resistance of the artificial lung used in this study is comparable with the resistance of the native pulmonary vascular bed of normal patients. However, when exposed to pulsatile flow, the lack of compliance and the presence of abnormal pulse wave reflections result in an impedance at the first harmonic nearly 10-fold higher than that seen in normal lungs. The consequences of elevated input impedance on cardiac function in vivo have not been described. A previous study using isolated hearts in a modified extracorporeal circuit demonstrated abnormal ventricular function with reductions in outflow compliance and elevations in impedance. 11 Addition of a compliance chamber that reduces impedance may prevent these abnormalities.
The results of the lumped-parameter model are useful in interpreting the bench-top simulation and can provide guidance in constructing a compliance chamber. Two main considerations for this design are reducing the flow pulsatility across the artificial lung membrane and decreasing first harmonic impedance. Because higher harmonics of flow and pressure are relatively small, the first harmonic provides a good indication of how closely the artificial and native circulations match.
As shown in Figure 4, values of T in the range of one and smaller decrease fiber BFP. Matching the time scale of flow pulsations with the time scale of the resistance-compliance circuit allows the compliance chamber volume to increase during ejection and then decrease before the next cycle. If the time scale of the circuit is significantly faster than the period of pulsations, the reservoir quickly returns stored volume. Outflow becomes similar to inflow, minimizing the effectiveness of compliance. Lowering R reduces first harmonic impedance, indicating that having most of the circuit resistance distal to the compliance chamber optimizes its efficiency. Additionally, BFP is also lower when R is small, demonstrating the relationship between first harmonic impedance and BFP. A more efficient compliance chamber design will dampen flow pulsations and reduce impedance at the first harmonic. From the lumped-parameter model, a compliance chamber design should be such that the time scale of the circuit is matched to the time scale of the flow and that most of the circuit resistance is positioned after the compliance element.
The prototype compliance chamber design used in this study reduced first harmonic impedance from 4.6 to 1.0 Woods Units, without increasing steady flow resistance (Figures 6 and 7). This nearly 80% reduction is a significant improvement in pulsatile load, although we were not quite able to achieve the 0.5 Woods Units Z1 typically seen in normal patients. Based on the lumped-parameter model, one reason for the inability achieving the desired Z1 is possibly related to the increased Z0 observed at higher pneumatic pressures (Figure 7). In the terminology of the lumped-parameter model, C may have been increased, but R was also increased, preventing additional reductions in Z1. Further studies using analytical techniques such as computational fluid dynamics will address many of the design limitations, and potentially allow prototype refinement to more closely approximate normal pulmonary input impedance.
External compression maximizes compliance and alters its time scale by augmenting diastolic emptying and maximizing its capacitance before the initiation of systole. However, compression of a deformable material will reduce the cross-sectional area of the blood flow path, potentially increasing steady flow resistance. In our simulation, once compression exceeded the hydrostatic forces of the “left atrium,” there was a consistent rise in Z0, markedly so in several cases (Figure 7). This drawback could be avoided, however, with the use of the stented compliance reservoir, preventing its complete collapse.
A compliance chamber intended for prolonged use with an artificial lung must adhere to some basic guidelines: durability, biocompatibility, and adjustability. Once subjected to repeated stress cycles, elastic materials with known biocompatibility will develop fatigue and eventual failure. This loss of compliance will inevitably elevate impedance and potentially result in right ventricular failure. Loss of elasticity may also produce stagnation and promote thrombosis, an equally catastrophic consequence. Using pneumatic compression on a deformable but nonelastic material, fatigue can be avoided. Additionally, air pressure can be continuously monitored and adjusted. In our experimental simulation, optimal impedance was achieved when compression slightly exceeded “left atrial” hydrostatic pressure. As physiologic conditions change, such as alterations in left atrial pressure, heart rate, or stroke volume, external compression can be modified to maintain the necessary compliance and adjust its time scale, thus compensating to minimize cardiac load. Servoregulation can also be incorporated to provide smooth automation.
This study tested a design for an artificial lung compliance chamber, guided by a theoretical three element lumped-parameter model. The low resistance but noncompliant artificial lung demonstrated similar resistance but significantly higher impedance when compared with the normal pulmonary circulation. Addition of an in-series compliance chamber significantly reduced first harmonic impedance, without increasing resistance. The design incorporates a deformable biocompatible material, optimally compliant independent of its mechanical elasticity. Further refinements using analytic tools and bench-top simulation should allow the development of a design that closely reproduces normal pulmonary input impedance in a practical and functional package. Correlation with in vivo testing will be performed to evaluate the effect of compliance on right ventricular function.
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Copyright © 2003 by the American Society for Artificial Internal Organs
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