Evaluation of a respiratory assist catheter that uses an impeller within a hollow fiber membrane bundle.

Respiratory assist using an intravenous catheter may be a potential treatment for patients suffering from acute or acute-on-chronic lung failure. The objective of this study was to evaluate a novel respiratory catheter that uses an impeller within the fiber bundle to enhance gas exchange efficiency, thus requiring a smaller fiber bundle and insertional size (25 Fr) and permitting simple percutaneous insertion. Bench testing of gas exchange in deionized water was used to evaluate eight impeller designs. The three best performing impeller designs were evaluated in acute studies in four calves (122 + or - 10 kg). Gas exchange increased significantly with increasing impeller rotation rate. The degree of enhancement varied with impeller geometry. The maximum gas exchange efficiency (exchange per unit surface area) for the catheter with the best performing impeller was 529 + or - 20 ml CO(2)/min/m(2) and 513 + or - 21 ml CO(2)/min/m(2) for bench and animal studies, respectively, at a rotation rate of 20,000 rpm. Absolute CO(2) exchange was 37 and 36 ml CO(2)/min, respectively. Active mixing by rotating impellers produced 70% higher gas exchange efficiency than pulsating balloon catheters. The sensitivity of gas exchange to impeller design suggests that further improvements can be made by computational fluid dynamics-based optimization of the impeller.

Flow visualization study of a novel respiratory assist catheter.

Respiratory assist using intravenous catheters may be a potential therapy for patients with acute and acute-on-chronic lung failure. An important design constraint is respiratory catheter size, and new strategies are needed that enable size reduction while maintaining adequate gas exchange. Our group is currently developing a percutaneous respiratory assist catheter (PRAC) that uses a rotating bundle of hollow fiber membranes to enhance CO(2) removal and O(2) supply with increasing bundle rotation rate. In this study, particle image velocimetry (PIV) was used to analyze the fluid flow patterns and velocity fields surrounding the rotating fiber bundle of the PRAC. The goal of the study was to assess the rotational flow patterns within the context of the gas exchange enhancement that occurs with increasing fiber bundle rotation. A PRAC prototype was placed in a 1-in. internal diameter test section of an in vitro flow loop designed specifically for PIV studies. The rotation rate of the PRAC was varied between 500 and 7000 rpm, and PIV was used to determine the velocity fields in the primary (r-theta) and secondary (r-z) flow planes. The secondary flow exhibited time-varying and incoherent vortices that were consistent with the classical Taylor vortices expected for Taylor numbers (Ta) corresponding to the rotation speeds studied (2200 < Ta < 31 000). In the primary flow, the tangential velocity exhibited boundary layers of less than (1/2) mm adjacent to the fiber bundle and vessel wall. The estimated shear stress associated with the Taylor vortices was approximately 11 dyne/cm(2) at 7000 rpm and was over 10 times smaller than the shear stress in the primary flow boundary layers.

Impact of graft volume reduction for oversized grafts after lung transplantation on outcome in recipients with end-stage restrictive pulmonary diseases.

BACKGROUND: Optimal size matching is critical to avoid problems from oversized grafts used in lung transplantation for restrictive pulmonary diseases in patients with a small chest cavity. Although graft volume reduction (GVR) is useful to overcome related disparities, its merits and demerits remain unclear. METHODS: We performed 342 lung transplants during the period of January 2003 to April 2007. Of the lung transplant recipients, 167 recipients had end-stage restrictive pulmonary diseases, with 25 (15%) receiving grafts considered to be oversized because of height disparity. The present retrospective analysis was conducted to compare between patients with size-matched and oversized grafts, and patients who did (GVR group, n = 9) and did not (non-GVR group, n = 16) undergo GVR for an oversized graft. RESULTS: Pulmonary functional improvement after 6 months was better in size-matched patients in view of percent forced vital capacity (FVC%) increase (29.8% vs 21.2%, p < 0.05), whereas long-term survival was not significantly different between the size-matched and oversized groups. Compared with the GVR group, the non-GVR group had a significantly higher incidence of short-term complications leading to respiratory failure (50% vs 11.1%, p < 0.05), whereas functional improvement was significantly worse in the non-GVR group (FVC% increase: 32.8% vs 19.9%, p < 0.05). However, overall patient survival at 3 years was not significantly different (non-GVR: 67%; GVR: 75%). CONCLUSIONS: An oversized graft may lead to a higher incidence of short-term clinical complications with reduced pulmonary function improvement post-operatively in lung transplantation recipients with end-stage restrictive pulmonary diseases. The decision of whether to carry-out GVR at the time of transplantation with an oversized graft to improve outcome is of critical importance.

Evaluation of fiber bundle rotation for enhancing gas exchange in a respiratory assist catheter.

Supplemental oxygenation and carbon dioxide removal through an intravenous respiratory assist catheter can be used as a means of treating patients with acute respiratory failure. We are beginning development efforts toward a new respiratory assist catheter with an insertional size <25F, which can be inserted percutaneously. In this study, we evaluated fiber bundle rotation as an improved mechanism for active mixing and enhanced gas exchange in intravenous respiratory assist catheters. Using a simple test apparatus of a rotating densely packed bundle of hollow fiber membranes, water and blood gas exchange levels were evaluated at various rotation speeds in a mock vena cava. At 12,000 RPM, maximum CO2 gas exchange rates were 449 and 523 mL/min per m2, water and blood, respectively, but the rate of increase with increasing rotation rate diminished beyond 7500 RPM. These levels of gas exchange efficiency are two- to threefold greater than achieved in our previous respiratory catheters using balloon pulsation for active mixing. In preliminary hemolysis tests, which monitored plasma-free hemoglobin levels in vitro over a period of 6 hours, we established that the rotating fiber bundle per se did not cause significant blood hemolysis compared with an intra-aortic balloon pump. Accordingly, fiber bundle rotation appears to be a potential mechanism for increasing gas exchange and reducing insertional size in respiratory catheters.

Blood biocompatibility assessment of an intravenous gas exchange device.

To treat acute lung failure, an intravenous membrane gas exchange device, the Hattler Catheter, is currently under development. Several methods were employed to evaluate the biocompatibility of the device during preclinical testing in bovines, and potential coatings for the fibers comprising the device were screened for their effectiveness in reducing thrombus deposition in vitro. Flow cytometric analysis demonstrated that the device had the capacity to activate platelets as evidenced by significant increases in circulating platelet microaggregates and activated platelets. Thrombus was observed on 20 +/- 6% of the surface area of devices implanted for up to 53 h. Adding aspirin to the antithrombotic therapy permitted two devices to remain implanted up to 96 h with reduced platelet activation and only 3% of the surface covered with thrombus. The application of heparin-based coatings significantly reduced thrombus deposition in vitro. The results suggest that with the use of appropriate antithrombotic therapies and surface coatings the Hattler Catheter might successfully provide support for acute lung failure without thrombotic complications.

Investigating the effects of random balloon pulsation on gas exchange in a respiratory assist catheter.

We are developing an intravenous respiratory assist catheter, which uses hollow-fiber membranes wrapped around a pulsating balloon that increases oxygenation and CO2 removal with increased balloon pulsation. Our current pulsation system operates with a constant rate of pulsation and delivered balloon volume. This study examined the hypothesis that random balloon pulsation would disrupt fluid entrainment within the fiber bundle and increase our overall gas exchange. We implemented two different modes for random (rates and delivered volume) versus constant pulsation. The impact on gas exchange was measured in a 3 l/min water flow loop at 37 degrees C. CO2 gas exchange for randomized beat rate mode was comparable to its corresponding average constant pulsation (e.g., constant 286 beats/min versus randomized 200-400 beats/min was 299.5+/-0.9 and 302.2+/-1.4 ml/min/m, respectively). Random volume mode CO2 exchange was also comparable to constant delivered balloon volume (100% inflation and deflation) (e.g., 294.3+/-0.6 and 301.1+/-1.7 ml/min/m, random 50-100% inflation and constant, respectively). Greater active mixing was seen with constant pulsation as compared with randomly changing the parameters of balloon pulsation.

Flow visualization study of a pulsating respiratory assist catheter.

Our group is currently developing an intravenous respiratory assist device that uses a centrally located pulsatile balloon within a hollow fiber bundle to enhance gas exchange rate via active mixing mechanism. We tested the hypothesis that the non-symmetric inflation and deflation of the balloon lead to both nonuniform balloon-generated secondary flow and nonuniform gas exchange rate in the fiber bundle. The respiratory catheter was placed in a 1-in. internal diameter rigid test section of an in vitro flow loop (3 L/min deionized water). Particle image velocimetry (PIV), which was used to map the velocity vector field in the lateral cross-section, showed that the balloon pulsation generated a nonuniform fluid flow surrounding the respiratory assist catheter. PIV was also used to characterize the fiber bundle movement, which was induced by the balloon pulsation. Gas permeability coefficient of the device was evaluated by using both the fluid velocity and the relative velocity between the fluid and the fiber bundle. The highest difference in the gas permeability coefficient predicted by using the relative velocity was about 17% to 23% (angular direction), which was more uniform than the 49% to 59% variation predicted by using the fluid velocity. The movement of the fiber bundle was responsible for reducing the variation in the fluid velocity passing through the bundle and for minimizing the nonuniformity of the gas permeability coefficient of the respiratory assist catheter.

Early outcomes in human lung transplantation with Thymoglobulin or Campath-1H for recipient pretreatment followed by posttransplant tacrolimus near-monotherapy.

OBJECTIVES: Acute and chronic rejection remain unresolved problems after lung transplantation, despite heavy multidrug immunosuppression. In turn, the strong immunosuppression has been responsible for mortality and pervasive morbidity. It also has been postulated to interdict potential mechanisms of alloengraftment. METHODS: In 48 lung recipients we applied 2 therapeutic principles: (1) recipient pretreatment with antilymphoid antibody preparations (Thymoglobulin [SangStat, Fremont, Calif] or Campath [alemtuzumab; manufactured by ILEX Pharmaceuticals, LP, San Antonio, Tex; distributed by Berlex Laboratories, Richmond, Calif]) and (2) minimal posttransplant immunosuppression with tacrolimus monotherapy or near-monotherapy. Our principal analysis was of the events during the critical first 6 posttransplant months of highest immunologic and infectious disease risk. Results were compared with those of 28 historical lung recipients treated with daclizumab induction and triple immunosuppression (tacrolimus-prednisone-azathioprine). RESULTS: Recipient pretreatment with both antilymphoid preparations allowed the use of postoperative tacrolimus monotherapy with prevention or control of acute rejection. Freedom from rejection was significantly greater with Campath than with Thymoglobulin (P = .03) or daclizumab (P = .05). After lymphoid depletion with Thymoglobulin or Campath, patient and graft survival at 6 months was 90% or greater. Patient and graft survival after 9 to 24 months is 84.2% in the Thymoglobulin cohort, and after 10 to 12 months, it is 90% in the Campath cohort. There has been a subjective improvement in quality of life relative to our historical experience. CONCLUSION: Our results suggest that improvements in lung transplantation can be accomplished by altering the timing, dosage, and approach to immunosuppression in ways that might allow natural mechanisms of alloengraftment and diminish the magnitude of required maintenance immunosuppression.

Evaluation of local gas exchange in a pulsating respiratory support catheter.

An intravenous respiratory support catheter, the next generation of artificial lungs, is being developed in our laboratory to potentially support acute respiratory failure or patients with chronic obstructive pulmonary disease with acute exacerbations. A rapidly pulsating 25 ml balloon inside a bundle of hollow fiber membranes facilitates supplemental oxygenation and CO2 removal. In this study, we hypothesized that non-uniform gas exchange in different regions of this fiber bundle was present because of asymmetric balloon collapse and the interaction of longitudinal flow. Four quarter regions and two rings around the central balloon were selectively perfused to evaluate local gas exchange in a 3.18 cm test section using helium as the sweep gas. Quarter region CO2 exchange rates at 400 beats per minute were 156.8 +/- 0.8, 162.5 +/- 1.8, 157.2 +/- 0.2, and 196.6 +/- 0.8 ml/min/m2 (top, front, bottom, and back, respectively). The back section, adjacent to convex balloon collapse, had 17-20% higher exchange than the other sections caused by higher relative velocities past its stationary fibers. Inner and outer ring maximum pulsation gas exchange rates were 174.4 +/- 1.8 and 174.6 +/- 0.9 ml/min/m2, respectively, showing that fluid flow was equally distributed throughout the fiber bundle.

Evaluation of plasma resistant hollow fiber membranes for artificial lungs.

Hollow fiber membranes (HFMs) used in artificial lungs (oxygenators) undergo plasma leakage (or wetting) in which blood plasma slowly fills the pores of the fiber wall, plasma leaks into gas pathways, and overall gas exchange decreases. To overcome this problem plasma resistant fibers are being developed that are skinned asymmetric or composite symmetric versions of microporous oxygenator fibers. This report evaluates several candidate plasma resistant HFMs in terms of their gas permeance and plasma resistance as measured in a surfactant wet out test. Five candidate fibers were compared with each other and with a control fiber. CO2 and O2 gas permeance (in ml/s/cm2/cm Hg) in the plasma resistant fibers ranged from 3.15E-04 to 1.71E-03 and 3.40E-04 to 1.08E-03, respectively, compared with 1.62E-02 and 1.77E-02 for the control fiber. Maximum dye bleed through for the plasma resistant fibers in the forced wet out test were significantly less than for the control fiber. CO2 gas permeance of a plasma resistant fiber imposes the greatest constraint upon artificial lung design for sufficient gas exchange. However, our results suggest sufficient plasma resistance can be achieved using special skinned and composite HFMs while maintaining an acceptable CO2 gas permeance for a broad range of artificial lung applications.

Development of a balloon volume sensor for pulsating balloon catheters.

Helium pulsed balloons are integral components of several cardiovascular devices, including intraaortic balloon pumps (IABP) and a novel intravenous respiratory support catheter. Effective use of these devices clinically requires full inflation and deflation of the balloon, and improper operating conditions that lead to balloon under-inflation can potentially reduce respiratory or cardiac support provided to the patient. The goal of the present study was to extend basic spirographic techniques to develop a system to dynamically measure balloon volumes suitable for use in rapidly pulsating balloon catheters. The dynamic balloon volume sensor system (DBVSS) developed here used hot wire anemometry to measure helium flow in the drive line from console to catheter and integrated the flow to determine the volume delivered in each balloon pulsation. An important component of the DBVSS was an algorithm to automatically detect and adjust flow signals and measured balloon volumes in the presence of gas composition changes that arise from helium leaks occurring in these systems. The DBVSS was capable of measuring balloon volumes within 5-10% of actual balloon volumes over a broad range of operating conditions relevant to IABP and the respiratory support catheter. This includes variations in helium concentration from 70-100%, pulsation frequencies from 120-480 beats per minute, and simulated clinical conditions of reduced balloon filling caused by constricted vessels, increased driveline, or catheter resistance.

Acute in vivo testing of a respiratory assist catheter: implants in calves versus sheep.

A respiratory catheter that is inserted through a peripheral vein and placed within the vena cava is being developed for CO2 removal in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). The catheter uses a rapidly pulsating balloon to enhance gas exchange. In this study, the CO2 removal performance of our catheter was assessed in acute sheep implants and compared with calf implants, primarily because sheep have cardiac outputs (CO) that are more comparable with human CO and lower than calves. Respiratory catheters (25 mL balloon, 0.17 m2) were inserted acutely in sheep (n = 2) and calves (n = 6) through the jugular vein and placed within the vena cava in two positions: spanning the right atrium (RA) and within the inferior vena cava (IVC). The postinsertion CO in the sheep ranged from 4.1 to 7.2 L/min compared with 6.2 to 15.5 L/min for the calves. The maximum CO2 removal rates (vCO2) were 297 ml/min/m2 (calf) and 282 ml/min/m2 (sheep) in the RA position and 240 ml/min/m2 (calf) and 248 ml/min/m2 (sheep) in the IVC position. The respective removal rates between animal models were not statistically different (p values > 0 .05 for all data sets). The dependence of the vCO2 on balloon pulsation was also not statistically different between the animal models.

A comparative in vitro hemolysis study of a pulsating intravenous artificial lung.

A study was conducted to measure and compare the levels of hemolysis generated by an intravenous membrane oxygenation device referred to as the Intravenous Membrane Oxygenator (IMO) in previous literature. The device is comprised of several hundred hollow fiber membranes of approximately 40 cm in length that are woven in a fabric and wrapped around a centrally positioned balloon. The balloon, which is similar in shape and volume to an intra-aortic balloon, is rapidly inflated and deflated up to 300 bpm to augment gas exchange. To evaluate the hemolytic nature of this device, an in vitro test system was developed, consisting of two identical test loops, each incorporating a device test section of 1 inch in diameter, a heat exchanger, a Biomedicus pump head, a compliance bag, a venous reservoir bag, and Tygon tubing. Both loops were primed with 1.5 L of a bovine blood solution and run simultaneously at 37 degrees C for 6 hours at 4 L/min. Hematocrit and plasma free hemoglobin concentration were measured every 30 minutes to monitor hemolysis within each loop. This methodology was used to compare the hemolysis of the device at maximal pulsation with that of the control loop with an empty test section, as well as with a pulsing balloon of the same volume without any fibers. The results suggest that the hemolytic nature of the pulsating intravenous oxygenator is consistent with that of an intra-aortic balloon, a clinically used device not associated with any complications due to hemolysis.

A respiratory gas exchange catheter: in vitro and in vivo tests in large animals.

OBJECTIVES: Acute respiratory failure is associated with a mortality of 40% to 50%, despite advanced ventilator support and extracorporeal membrane oxygenation. A respiratory gas exchange catheter (the Hattler Catheter) has been developed as an oxygenator and carbon dioxide removal device for placement in the vena cava and right atrium in the treatment of acute respiratory failure to improve survival. METHODS: Differing from a previously clinically tested intravenous gas exchange device (ie, IVOX), the Hattler Catheter incorporates a small, pulsating balloon surrounded by hollow fibers. The pulsating balloon redirects blood toward the fibers, enhances red cell contact with the membrane, and significantly improves gas exchange so that smaller catheter devices are still efficient on insertion and can be inserted through the jugular or femoral vein. Devices were tested in mock circulatory loops and in short-term (8 hours) and long-term (4 days) experiments in calves to study the effect of various sized balloons and the anatomic location of the device in the venous system as a function of hemodynamics and gas exchange. RESULTS: In vitro performance in water demonstrates an oxygen delivery (Vo(2)) of 140 +/- 8.9 mL. min(-1). m(-2) and a carbon dioxide removal (Vco(2)) of 240 +/- 6.1 mL. min(-1). m(-2). Acute in vivo experiments demonstrate a maximum carbon dioxide consumption of 378 +/- 11.2 mL. min(-1). m(-2). Devices positioned in the right atrium had an average carbon dioxide exchange of 305 mL. min(-1). m(-2), whereas in the inferior vena cava position carbon dioxide exchange was 255 mL. min(-1). m(-2). Devices have been tested long term in calves, with gas exchange rates maintained over this time interval (carbon dioxide consumption, 265 +/- 35 mL. min(-1). m(-2)). Plasma-free hemoglobin levels at the end of 4 days have been 4.8 +/- 3.2 mg/dL. Hemodynamic measurements, including a decrease in cardiac outputs and increased mean pressure decreases across the device become significant only with the larger balloon (40-mL) devices (P <.05, 40-mL vs 13-mL devices). Autopsies show no end-organ damage. The device linearly increases its carbon dioxide output with progressive hypercapnea, predicting its ability to meet tidal volume reduction in the therapy of respiratory failure. CONCLUSIONS: Progress has been made toward developing an intravenous gas exchange catheter to provide temporary pulmonary support for patients in acute respiratory failure.

Effect of vessel compliance on the in-vitro performance of a pulsating respiratory support catheter.

Intravena caval respiratory support (or membrane oxygenation) is a potential therapy for patients with acute respiratory insufficiency. A respiratory support catheter is being developed that consists of a bundle of hollow fiber membranes with a centrally positioned pulsating balloon to enhance gas exchange. This study examined the influence of vessel compliance on the gas exchange performance of the pulsating respirator, support catheter. Polyurethane elastic tubes were fabricated with compliance comparable to that measured in bovine vena cava specimens. The gas exchange performance of the respiratory catheter was studied in an in-vitro flow loop using either the model compliant tube or a rigid tube as a "mock" vena cava. Balloon pulsation enhanced gas exchange comparably in both rigid and model compliant vessels up to 120 bpm pulsation frequency. Above 120 bpm gas exchange increased with further pulsation in the rigid tube, but no additional increase in gas exchange was seen in the compliant tube. The differences above 120 bpm may reflect differences in the compliance of the elastic tube versus the natural vena cava.

Lung and heart-lung transplantation at the University of Pittsburgh: 1982-2002.

The University of Pittsburgh lung transplantation program began in 1982 and through 2002 we have performed 576 lung and 101 heart-lung transplants. One-, 3- and 5-year survival rates over the past decade have been 77%, 62% and 55%, respectively, comparing favorably to ISHLT registry outcomes of 73%, 57% and 46%. We continue to utilize a very thorough evaluation process but have been flexible and aggressive with potential recipients with regard to age, coronary artery disease and disease state (eg., scleroderma). Despite worldwide progress in the field of lung transplantation, many difficulties remain. The limited number of lungs deemed acceptable for transplantation continues to hinder application to a greater number of patients. Our efforts in this regard have focused on cooperation with our OPO in education and detailed donor management protocols. Chronic rejection also remains a major difficulty frequently leading to death. Recent work utilizing aerosol cyclosporine in patients with established chronic rejection suggests that this therapy may prolong life. We are also hopeful that recently initiated therapies utilizing T-cell induction strategies may contribute to further improvement in outcomes.