Sean Chambers

The paracorporeal artificial lung improves 5-day outcomes from lethal smoke/burn-induced acute respiratory distress syndrome in sheep

BACKGROUND Our low-impedence, paracorporeal artificial lung (PAL) prototype is well-tolerated in-series with the normal sheep pulmonary circulation. Using our lethal dose 80% to 100% smoke/burn acute respiratory distress syndrome (ARDS) sheep model, we compared PAL to volume-controlled mechanical ventilation (VCMV) in a prospective, randomized, controlled, unblinded, 5-day outcome study. METHODS Fourteen sheep were randomized to PAL (n = 8) versus VCMV (n = 6) to assess outcome. For PAL, arterial cannulas were anastomosed to the proximal and distal main pulmonary artery with an interposing snare diverting full flow through a paracorporeal loop. Acute respiratory distress syndrome was induced in both groups (48 breaths smoke insufflation, third degree burn on 40% of total body surface area). When acute respiratory distress syndrome criteria were met (24 to 30 hours after injury), the PAL was interposed in the paracorporeal loop. Both groups were managed with a VCMV algorithm minimizing tidal volume, ventilator rate, and fractional inspired concentration of oxygen (FiO2). RESULTS Six of eight PAL versus 1 of 6 VCMV sheep survived the 5-day study. In PAL, cardiac output, mean arterial pressure, pulmonary artery pressure, left atrial pressure, and central venous pressure remained stable. Average PAL gas transfer was 218.6 +/- 17.7 mL/min O2 and 183.0 +/- 27.8 mL/min CO2. Ventilator settings 48 hours after lung injury in PAL were significantly lower (p < 0.05) than VCMV (TV 210 versus 425 mL; respiratory rate 6 versus 29 breaths/min; minute ventilation 1.2 versus 10.8 L/min; FiO2 21 versus 100%). Likewise, PaO2/FiO2 ratio was normalized in PAL and still met acute respiratory distress syndrome criteria in VCMV. The PAL wet/dry ratio was significantly lower than VCMV (6.36 +/- 0.63 versus 11.85 +/- 1.54; p = 0.008). CONCLUSIONS In a prospective, randomized, controlled, unblinded, outcomes study, PAL decreased ventilator-induced lung injury in a lethal dose 80% to 100% ARDS model to improve 5-day survival.

Improved right heart function with a compliant inflow artificial lung in series with the pulmonary circulation

BACKGROUND We previously reported a 50% incidence of immediate right heart failure using a rigidly housed, noncompliant inflow artificial lung in series with the pulmonary circulation in a healthy ovine survival model. Three device modifications resulted: (1) an inflow cannula compliance chamber, (2) an inlet blood flow separator, and (3) modification of the artificial lung outlet geometry, all to reduce resistance and mimic the compliance of the pulmonary vascular bed. METHODS In 7 sheep, arterial grafts were anastomosed end-to-side to the proximal and distal main pulmonary artery, with the paracorporeal artificial lung interposed. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the artificial lung for up to 72 hours. RESULTS Six of 7 sheep exhibited good cardiac function throughout the test period: mean central venous pressure was 6.8 mm Hg (range, 4 to 11 mm Hg), mean cardiac output, 4.17 +/- 0.12 L/min (range, 2.4 to 6.3 L/min); before and after device mean pulmonary arterial pressure, 21.8 and 18.5 mm Hg, and left atrial pressure, 10.8 mm Hg. CONCLUSIONS This modified artificial lung prototype with an inflow compliance chamber, blood flow separator, and modified outlet geometry has greatly improved cardiac function and initial survival in our healthy ovine model.

Effect of Artificial Lung Compliance on in Vivo Pulmonary System Hemodynamics

This study examined the effect of artificial lung compliance (C) on pulmonary system (PS) impedance and right ventricular function during in-series attachment of the MC3 Biolung in adult sheep. Compliances, C, of 0–20 ml/mm Hg were tested at the Biolung inlet. Results indicate the PS 0th harmonic input impedance modulus was not affected by C. The PS first harmonic input impedance modulus (Z1) was 10.9 ± 3.2 mm Hg/(l/min) at C = 0 ml/mm Hg and minimized to 2.41 ± 0.79 mm Hg/(l/min) at C ≥ 0.5 ml/mm Hg. Cardiac output was 58% ± 10% of its pre-Biolung attachment, baseline value at C = 0 ml/mm Hg and was maximized to an average of 75% ± 11% at C ≥ 0.5 ml/mm Hg. The left ventricular lateral-to-anteroposterior axis length ratio, which decreases with leftward septal shift, increased with C from 0.52 ± 0.12 at C = 0 ml/mm Hg to 0.76 ± 0.06 at C = 5 ml/mm Hg (p < 0.05), but decreased slightly with C at C > 5 ml/mm Hg. Therefore, the ideal C for right ventricular function is at least 0.5 ml/mm Hg and may be as high as 5 ml/mm Hg to minimize septal shift.

In vitro fluid mechanical effects of thoracic artificial lung compliance.

This in vitro study sought to determine what compliance minimizes thoracic artificial lung impedance and pump power output. A pulsatile pump drove 3.0 cP glycerol through a circuit consisting of an MC3 Biolung® preceded by a piston-cylinder (PC, n = 5) chamber with a variable compliance or a polyurethane (n = 4) chamber with a fixed, yet pressure-dependent, compliance. Each chamber was tested at flow rates of 1.8, 3.0, and 5.0 l/min and heart rates of 60, 75, and 100 bpm. Compliances, C, from 0-20 ml/mm Hg were tested in the PC chamber. Instantaneous pump outlet flow and pressure were acquired for determination of device zeroth and first harmonic input impedance, Z0 and Z1, and pump steady and pulsatile output powers, Ps and Pp. PC chamber results indicate that Z0, Z1, Ps, and Pp were minimized at C > 1, 5, 0.5, and 4 ml/mm Hg, respectively. This suggests that C should be 1 ml/mm Hg at minimum and ideally 5 ml/mm Hg. The polyurethane chamber was statistically similar to the PC chamber at C = 1 ml/mm Hg when comparing Z0 and Ps, but was statistically inferior when comparing Z1 and Pp. The polyurethane compliance chamber, therefore, should be redesigned with greater compliance.

Extreme negative pressure does not cause erythrocyte damage in flowing blood

In extracorporeal circulation, negative pressure is thought to be a source of hemolysis. This study was designed to investigate the effects of extreme negative pressure on flowing blood. The study model was pipe flow. The hemolysis generated by negative pressure driven flow was compared with that generated by positive pressure driven flow of equal magnitude to control for the hemolytic effect of shear stress. A series of pressures (720, 600, 500, -500, -600, and -720 mm Hg; n = 8) was tested for pipe diameters of 0.04 and 0.16 cm, with a length-to-diameter ratio of 500. The pressure difference across the pipe (deltaP) was equal to the magnitude of the applied pressure. The hemolysis was quantified by the modified index of hemolysis (MIH). For both pipe diameters, MIH was found to not depend on the deltaP or the blood collection day (multiple regression analysis, p = 0.50 and p = 0.63, respectively). There was no statistically significant difference between the MIH for equal deltaP generated by positive or negative pressure (p = 0.50) for both pipe diameters tested. MIH did depend upon the pipe diameter, with 0.04 cm having higher MIH at all pressures (p = 0.0003). Thus, negative pressure is not a significant hemolytic factor in flowing blood.

Development of ambulatory arterio-venous carbon dioxide removal (AVCO2R) : The downsized gas exchanger prototype for ambulation removes enough CO2 with low blood resistance

We are developing an ultra compact gas exchanger to allow ambulation during arterial-venous CO2 removal (AVCO2R). The ambulatory AVCO2R gas exchanger (135 ml prime volume and 1.3 M2 gas exchange surface area) is made of polymethylpentene hollow fibers. The gas exchanger was attached to sheep carotid artery (12F) and jugular vein (14F) by percutaneous cannulae for 6 hours (n = 5). Device CO2 removal was measured and calculated at a constant blood flow rate of 1 L/min coupled with varying sweep gas from 1 to 15 L/min, and at constant sweep gas flow of 2 L/min coupled with varying blood flow from 0.5 to 1.25 L/min to determine capacity of CO2 removal at Pa CO2 = 40–50 mm Hg. Blood gases, CO2 removal and hemodynamics were recorded at 0, 3, and 6 hours. CO2 removal increased with sweep gas flow rate and with increase of device blood flow. Hemodynamics remained unchanged throughout study. Gas exchanger resistance remained stable at 2.3 ± 0.53 mm Hg/L/min. CO2 removal with 1 L/min blood flow and 2 L/min sweep gas was 110 ± 12 then stabilized at 85 ± 14 mL/min to 6 hours. The compact ambulatory AVCO2R gas exchanger achieves stable, near total CO2 removal for at least 6 hours with a simple arteriovenous shunt.

Toward ambulatory arteriovenous CO2 removal: Initial studies and prototype development

Extracorporeal arteriovenous carbon dioxide removal (AVCO2R) using percutaneous cannulae and a low resistance gas exchanger achieves near total CO2 removal, allowing lung rest and potentially improving survival. AVCO2R, redesigned to allow ambulation, has potential as treatment for severe chronic obstructive pulmonary disease or rehabilitation before lung transplant. The purposes of this study were to 1) determine the optimal ambulatory access for AVCO2 removal and 2) develop a prototype Ambulatory-AVCO2R gas exchanger. Initially, reinforced Gore-Tex 6 mm (two) and 8 mm (four) grafts were anastomosed to sheep carotid arteries and jugular veins as a loop in parallel to the cranial circulation to determine blood flow capabilities. Blood flow was 100–150 ml/min with a 14 gauge dialysis needle, and transected 6 mm Gore-Tex grafts achieved 500–900 ml blood flow, whereas transected 8 mm grafts achieved up to 2000 ml/min flow. The polytetrafluoroethylene (PTFE) loops were then connected to our newly developed ultra low resistance pumpless gas exchanger for ambulatory AVCO2R. The average pressure gradient across the prototype Ambulatory-AVCO2R gas exchangers (n = 5) was 2.8 ± 0.8 mm Hg, and mean CO2 removal was 104.8 ± 14.0 ml/min, with an average blood flow of 900 ml/min. We conclude that an 8 mm Gore-Tex reinforced graft arteriovenous loop supplies ample blood flow for our new ultra low resistance Ambulatory-AVCO2R to achieve near total CO2 removal.

Optional active compliance chamber performance in a pulmonary artery-pulmonary artery configured paracorporeal artificial lung

Introduction : Our group has developed a paracorporeal artificial lung (PAL) attached in a pulmonary artery (PA) to PA in series configuration to address profound respiratory failure and serve as a bridge to transplant and/or recovery. We recently designed, developed and converted our passive pre-PAL compliance chamber to an active, synchronized, counterpulsating assist device to relieve right heart strain and offset increased work placed on the right ventricle when the PAL is attached. In this study, we evaluated the safety and performance of both a valved and non-valved optional active compliance chamber (OACC) in a PA-PA PAL for right heart assistance in normal adult sheep. Methods : Eleven sheep (30—50 kg) were divided into non-valved OACC (n = 6) and valved (n = 5) OACC groups. To mimic pulmonary hypertension, a C-clamp was placed distal to the OACC-PAL and occluded until a 20% decrease in cardiac output (CO) was achieved. The OACC was activated, and right ventricular pressure (RVP), pulmonary artery pressure (PAP), mean arterial pressure (MAP) and CO were recorded. Results : All eleven animals tolerated the implantation of the OACC PAL. Activation of the OACC resulted in a significant increase in CO. Systolic and diastolic right ventricular pressure decreased in both groups. Lastly, counterpulsation increased the mean PAP in all animals and peak PAP reached 89 mmHg. Despite providing right heart assistance, synchronizing the counterpulsation was technically difficult, and the high peak PA pressures resulted in anastomotic bleeding in all animals and anastomotic breakdown in 4/11 animals. Conclusions : An OACC PAL perfused by the right ventricle applied in series with the pulmonary circulation reduces ventricular load and improves cardiac efficiency. These preliminary data suggest the potential of an artificial lung in unloading the strained right ventricle and acting as a bridge to transplantation. The augmented peak PA pressures, resulting in bleeding and anastomotic breakdown, and complexity in synchronizing the cardiac cycle with the pulsations of the augmented OACC, compromise this configuration. Perfusion (2007) 22, 81—86.

Determination of the in vivo cavitation nuclei characteristics of blood.

Cavitation has been documented in the in vitro testing of blood-handling devices. To predict whether cavitation will occur clinically, the nuclei content of blood and the threshold pressure for activation of the in situ nuclei must be characterized. A single-pass flow apparatus is described for determining the nuclei characteristics of blood. The flow apparatus consists of a syringe pump and a venturi-geometry hydrodynamic device, called a cavitation susceptibility meter (CSM). Blood is accelerated through the throat of the CSM, thus exposing the nuclei in the blood to a well-defined pressure profile. The apparatus was used in an ex vivo sheep model for the determination of the in vivo nuclei characteristics of blood. The active nuclei concentration of in vivo blood was measured to be at most 2.7 nuclei per liter of plasma at a minimum throat pressure of -1610 mm Hg gauge (i.e., tension of 900 mm Hg). At this pressure, bubble stability theory predicts the active nuclei to have a radius on the order of 0.3 microm. Based on these results, in vitro studies to determine the cavitation potential of blood-handling devices must utilize test fluids that contain a minimum nuclei size distribution and concentration. It cannot be assumed that in vivo blood is nuclei rich, such that it will cavitate at or near vapor pressure.

Characterization of a Bioprosthetic Bicuspid Venous Valve Hemodynamics and Implications for Mechanism of Valve Dynamics

of CCSVI. We hypothesize that the BA effect on clinical parameters is mediated by mechanical stimulation of perivascular autonomic fibers and is independent of vascular obstruction. The purpose of this study is to describe Trans-Vascular Autonomic Modulation (TVAM) in multiple sclerosis (MS) patients as a means of improving ANS dysfunction, comparing its safety and efficacy to the traditional BA. Methods: Twenty-one MS patients who presented with symptoms of cardiovascular ANS dysfunction underwent TVAM. These patients were compared with 20 MS patients who presented with CSSVI, and who underwent traditional BA. TVAM deviated from traditional BA in that target veins, bilateral internal jugular, azygos, and left renal veins, were each dilated regardless of the presence of vascular abnormalities. This also included treatment of patients without evidence of abnormality in any of the target veins, eliminating the possibility of vascular effect. The improvement in cardiovascular ANS function was indicated by determining R-R interval variations during deep breathing (MCR, E/I ratio), valsalva maneuver (valsalva ratio), and postural changes (30:15 postural ratio). Results: The safety profile of the TVAM procedure was similar to that of the traditional BA with no adverse events occurring in either group. However, TVAM increased MCR, E/I ratio, and postural ratio more significantly than the traditional BA. Postintervention, improvements were seen in the TVAM group relative to baseline for MCR (3.34 6 0.41 vs 2.44 6 0.48; 36.4%; P 1⁄4 .08), E/I ratio (1.11 6 0.01 vs 1.09 6 0.01; 1.8%; P 1⁄4 .3), valsalva ratio (1.95 6 0.09 vs 1.74 6 0.09; 12%; P 1⁄4 .10), and postural ratio (1.36 6 0.08 vs 1.04 6 0.09; 30.7%; P 1⁄4 .027). The postural ratio response in the TVAM group relative to baseline (1.36 6 0.08 vs 1.04 6 0.09; 30.7%; P 1⁄4 .027) demonstrated the largest change relative to postintervention postural ratio in the control group (1.36 6 0.08 vs 1.167 6 0.03; 16.5%; P 1⁄4 .016). Conclusions: TVAM-mediated deposition of mechanical energy to central veins by balloon dilation, including anatomically normal veins, can improve indicators of ANS dysfunction. The observed safety and efficacy of TVAM is encouraging, paving the way for the treatment of ANS dysfunction in pathological states other than MS. Further studies should investigate the response to TVAM in larger cohort. Characterization of a Bioprosthetic Bicuspid Venous Valve Hemodynamics and Implications for Mechanism of Valve Dynamics W. Tien, H. Chen, Z. Berwick, J. Krieger, S. Chambers, D. Dabiri, G. Kassab. University of Washington, Seattle, Wash; 3DT Holdings, LLC, Indianapolis, Ind; COOK Medical, Bloomington, Ind; Indiana University School of Medicine, Indianapolis, Ind