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The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS’s axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p> 0.05). This study demonstrates equivalent hemocompatibility of the PAS’s AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup.

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.9 m2surface area) gas exchanger, the pulmonary assist device, with a modified Heart Assist 5 pump fitting in a small wearable pack. Prototype PAS were attached to two sheep in venovenous configuration for 7 and 14 days, evaluating ability to remain thrombus free; maintain gas exchange and blood flow resistance; avoid biocompatibility-related complications while allowing safe ambulation. The PAS achieved 1.56 L/min of flow at 10.8 kRPM with a 24 Fr cannula in sheep one and 2.0 L/min at 10.5 kRPM with a 28 Fr cannula in sheep 2 without significant change. Both sheep walked freely, demonstrating the first application of truly ambulatory ECMO in sheep. While in vitrotesting evaluated PAS oxygen transfer rates of 104.6 ml/min at 2 L/min blood flow, oxygen transfer rates averaged 60.6 ml/min and 70.6 ml/min in studies 1 and 2, due to average hemoglobin concentrations lower than humans (8.9 and 10.5 g/dl, respectively). The presented cases support uncomplicated ambulation using the PAS.

Supplemental Digital Content is available in the text.Decompensated right ventricular failure (RVF) in patients with pulmonary hypertension (PH) is fatal, with limited treatment options. Novel mechanical circulatory support systems have therapeutic potential for RVF, but the development of these devices requires a large animal disease model that replicates the pathophysiology observed in humans. We previously reported an effective disease model of PH in sheep through ligation of the left pulmonary artery (PA) and progressive occlusion of the main PA. Herein, we report a case of acute decompensation with this model of chronic RVF. Gradual PA banding raised the RV pressure (maximum RV systolic/mean pressure = 95 mmHg/56 mmHg). Clinical findings and laboratory serum parameters suggested appropriate physiologic compensation for 7 weeks. However, mixed venous saturation declined precipitously on week 7, and creatinine increased markedly on week 9. By the 10th week, the animal developed dependent, subcutaneous edema. Subsequently, the animal expired during the induction of general anesthesia. Post-mortem evaluation revealed several liters of pleural effusion and ascites, RV dilatation, eccentric RV hypertrophy, and myocardial fibrosis. The presented case supports this model’s relevance to the human pathophysiology of RVF secondary to PH and its value in the development of novel devices, therapeutics, and interventions.

Supplemental Digital Content is available in the text.Microchannel artificial lungs may provide highly efficient, long-term respiratory support, but a robust predictive oxygen transfer (VO2) model is needed to better design them. To meet this need, we first investigated the predictive accuracy of Mikic, Benn, and Drinker’s advancing front (AF) oxygen transfer theory by applying it to previous microchannel lung studies. Here, the model that included membrane resistance showed no bias toward overprediction or underprediction of VO2(median error: −1.13%, interquartile range: [−26.9%, 19.2%]) and matched closely with existing theory. Next, this theory was expanded into a general model for investigating a family of designs. The overall model suggests that, for VO2= 100 ml/min, fraction of delivered oxygen (FDO2) = 40%, wall shear stress () = 30 dyn/cm2, and blood channel height = 20–50 μm, a compact design can be achieved with priming volume () = 5.8–32 ml; however, manifolding may be challenging to satisfy the rigorous total width () requirement (= 76–475 m). In comparison, 100–200 μm heights would yield larger dimensions (122–478 ml) but simpler manifolding (4.75–19.0 m). The device size can be further adjusted by varying FDO2, , or VO2. This model may thus serve as a simple yet useful tool to better design microchannel artificial lungs.

The compliant thoracic artificial lung (cTAL) has been studied in acute in vivoand in vitroexperiments. 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.

This study evaluated the effectiveness of an atrial septal defect (ASD) with venovenous extracorporeal membrane oxygenation (vv-ECMO) as a bridge to transplantation. Sheep (56 ± 3 kg; n = 7) underwent a right-sided thoracotomy to create the ASD (diameter = 1 cm) and place instrumentation and a pulmonary artery (PA) occluder. After recovery, animals were placed on ECMO, and the PA was constricted to generate a twofold rise in right ventricular (RV) systolic pressure. Sheep were then maintained for 60 hours on ECMO, and data were collected hourly. Five sheep survived 60 hours. One sheep died because of a circuit clot extending into the RV, and another died presumably because of an arrhythmia. Mean right ventricular pressure (mRVP) was 19 ± 3 mm Hg at baseline, averaged 27 ± 7 mm Hg over the experiment, but was not statistically significant (p= 0.27) due to one sheep without an increase. Cardiac output was 6.8 ± 1.2 Lmin at baseline, averaged 6.0 ± 1.0 Lmin during the experiment, and was statistically unchanged (p= 0.34). Average arterial oxygen saturation and PCO2over the experiment were 96.8 ± 1.4 and 31.8 ± 3.4 mm Hg, respectively. In conclusion, an ASD combined with vv-ECMO maintains normal systemic hemodynamics and arterial blood gases during a long-term increase in RV afterload.

We achieved ultralow fouling on target surfaces by controlled polymerization of carboxybetaine under ambient conditions. The polymerization process for grafting polymer films onto the surfaces was carried out in air and did not require any deoxygenation step or specialized equipment. This method allows one to conveniently introduce a nonfouling polymer network onto large substrates.

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, , on device impedance and blood flow patterns. Based on the results, the = 45° model was chosen for prototyping and in vitrotesting. Glycerol was pumped through this cTAL at 2, 4, and 6 Lmin at 80 and 100 beatsmin, and the zeroth and first harmonic impedance moduli, Z0and Z1, were calculated. Gas transfer testing was conducted at blood flow rates of 3, 5, and 7 Lmin. 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, Z0= 0.53 ± 0.06 mm Hg(Lmin) and Z1= 0.86 ± 0.08 mm Hg(Lmin) at 4 Lmin and 100 beatsmin. Outlet PO2and SO2values 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.

Recent thoracic artificial lung (TAL) prototypes have impedances lower than the natural lung. With these devices, proximal pulmonary artery (PA) to distal PA TAL attachment may be possible in patients without right ventricular dysfunction. This study examined the relationship between pulmonary system impedance and cardiac output (CO) to create TAL design constraints. A circuit with adjustable resistance and compliance (C) was attached in a PA–PA fashion with the pulmonary circulation of seven sheep with chronic pulmonary hypertension. The pulmonary system zeroth harmonic impedance modulus (Z0) was increased by 1, 2.5, and 4 mmHg(Lmin) above baseline. At each Z0, Cwas set to 0, 0.34, and 2.1 mlmmHg. The change in pulmonary system zeroth and first harmonic impedance moduli (Z0and Z1), the percent change in CO (CO), and the inlet and outlet anastomoses resistances were calculated for each situation. Results indicate that Z0(p< 0.001) but not Z1(p= 0.5) had a significant effect on COand that CO= −7.45Z0(R2= 0.57). Inlet and outlet anastomoses resistances averaged 0.77 ± 0.16 and 0.10 ± 0.19 mmHg(Lmin), respectively, and the relationship between COand TAL resistance, RT, in mmHg(Lmin) was determined to be CO= −(7.45f)×(RT0.87), in which f= the fraction of CO through the TAL. Thus, newer TAL designs can limit COto less than 10 if f< 0.75.

Coagulation upon blood-contacting biomaterials remains a problem for short- and long-term clinical applications. This study examined the ability of copper(II)-doped silicone surfaces to generate nitric oxide (NO) and locally inhibit coagulation. Silicone was doped with 3-m copper Cu(0) particles yielding 3 to 10 weight percent (wt%) Cu in 70-m thick Cu/silicone polymeric matrix composites (Cu/Si PMCs). At 3, 5, 8, and 10 wt% Cu doping, the surface expression of Cu was 12.1% ± 2.8%, 19.7% ± 5.4%, 29.0% ± 3.8%, and 33.8% ± 6.5%, respectively. After oxidizing Cu(0) to Cu(II) by spontaneous corrosion, NO flux, JNO(mol · cm−2· min−1), as measured by chemiluminescence, increased with surface Cu expression according to the relationship JNO(1.63%SACu− 0.81) × 10−11, R20.98, where %SACuis the percentage of surface occupied by Cu. NO flux at 10 wt% Cu was 5.35 ± 0.74 × 10−10mol · cm−2· min−1. The clotting time of sheep blood exposed to these surfaces was 80 ± 13 seconds with pure silicone and 339 ± 44 seconds when 10 wt% Cu(II) was added. Scanning electron microscopies (SEMs) of coatings showed clots occurred away from exposed Cu dendrites. In conclusion, Cu/Si PMCs inhibit coagulation in a dose-dependent fashion related to the extent of copper exposure on the coated surface.

Despite successful resuscitation of donors after circulatory determination of death (DCD) with extracorporeal support (ECS), the technique is limited by ethical concerns about donor management (heparinization) and the complexity to operate the ECS circuit. This work studies different timing of heparin administration and the effects of ECS-perfusion temperature. Cardiac arrest (CA) was induced in swine. Heparin studies, three groups: 1) PRE5, heparin 5 minutes before CA; 2) POST5, heparin 5 minutes after CA, plus 2 minutes external chest compressions; and 3) POST30, heparin with the initiation of ECS after 30 minutes CA. Perfusion temperature study, two groups: 1) normothermic, ECS-38.5°C after 30 minutes CA and 2) room temperature, ECS-25.5°C for the first 90 minutes, followed by ECS-38.5°C. Heparin studies: ECS target flows (>50 ml/kg/min) were not achieved in the POST30 group, affecting local organ perfusion as observed with poor bile (<4 ml/min) and urine output (<25 ml/min), when compared with the other groups (normal values). Temperature study: In both groups, ECS target flows were reached, and urine/bile output was restored. Heparinization 5 minutes after CA is equivalent to premortem heparinization in this ECS-DCD model. Heparinization after CA could reduce ethical concerns. Donors after circulatory determination of death were successfully resuscitated at both temperatures, suggesting that the heat exchanger/water heater can be removed to simplify the ECS circuit.

Total liquid ventilation (TLV) has the potential to provide respiratory support superior to conventional mechanical ventilation (CMV) in the acute respiratory distress syndrome (ARDS). However, laboratory studies are limited to trials in small animals for no longer than 4 hours. The objective of this study was to compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep weighing 53 ± 4 (SD) kg were anesthetized and ventilated with 100% oxygen. Oleic acid was injected into the pulmonary circulation until PaO2:FiO2≤60 mm Hg, followed by transition to a protective CMV protocol (n 5) or TLV (n 5) for 24 hours. Pathophysiology was recorded, and the lungs were harvested for histological analysis. Animals treated with CMV became progressively hypoxic and hypercarbic despite maximum ventilatory support. Sheep treated with TLV maintained normal blood gases with statistically greater PO2(p< 10−9) and lower PCO2(p< 10−3) than the CMV group. Survival at 24 hours in the TLV and CMV groups were 100% and 40%, respectively (p< 0.05). Thus, TLV provided gas exchange superior to CMV in this laboratory model of severe ARDS.

Donors after Cardiac Death (DCD) may reduce the organ scarcity; however, their use is limited because of warm ischemia time. Fortunately, this is less important in a subclass of DCD called expected (e-DCD), those with irreversible but incomplete brain injury. This study analyzed hemodynamic/pulmonary data to establish a clinically relevant model of cardiac death that would simulate an e-DCD setting. Hemodynamics, pulmonary artery flows, arterial blood gasses, and left atrial pressure were recorded q 5 minutes in anesthetized swine. After baseline data collection, the ventilator was discontinued and heparin was administered. Cardiac death was defined: as asystole, or mean arterial presusure ≤25 mm Hg with a pulse pressure ≤20 mm Hg. The time to death was approximately 14.8 minutes. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. The hyperdynamic reflex response was followed by hypotension, bradycardia, and finally asystole or ventricular fibrillation. The protocol of withdrawal of ventilation, systemic anticoagulation, determination of death was developed to closely resemble the clinical e-DCD scenario. The physiologic changes that happen before death in DCD were described. An e-DCD model that can be used in studies related to organ transplantation was established.

The purpose of this study was to describe the hemolytic effects of both negative pressure and an air-blood interface independently and in combination in an in vitrostatic blood model. Samples of fresh ovine or human blood (5 ml) were subjected to a bubbling air interface (0–100 ml/min) or negative pressure (0–600 mm Hg) separately, or in combination, for controlled periods of time and analyzed for hemolysis. Neither negative pressure nor an air interface alone increased hemolysis. However, when air and negative pressure were combined, hemolysis increased as a function of negative pressure, the air interface, and time. Moreover, when blood samples were exposed to air before initiating the test, hemolysis was four to five times greater than samples not preexposed to air. When these experiments were repeated using freshly drawn human blood, the same phenomena were observed, but the hemolysis was significantly higher than that observed in sheep blood. In this model, hemolysis is caused by combined air and negative pressure and is unrelated to either factor alone.

Attachment of thoracic artificial lungs (TALs) can increase right ventricular (RV) afterload and decrease cardiac output (CO) under certain conditions. However, there is no established means of predicting the extent of RV dysfunction. The zeroth harmonic impedance modulus, Z0, was thus examined to determine its effectiveness at predicting CO during high afterload TAL attachment. The MC3 Biolung was attached in four adult sheep groups based on baseline (BL) pulmonary vascular resistance and TAL attachment mode: normal, parallel (n 7); normal, series (n 7); chronic pulmonary hypertension, parallel (n 5), and chronic pulmonary hypertension, series (n 5). The resistance of each attachment mode was increased incrementally and instantaneous pulmonary system hemodynamic data were acquired at each increment. The change in Z0from BL, Z0, and percent change in CO (CO%) were then calculated to determine their relationship. The CO%varied significantly with Z0(p< 10−40) and Z02(p< 10−4) but not with the attachment and pulmonary hemodynamics group. The relationship between the variables for all sheep groups was CO%0.215Z02− 7.14Z02.94 (R20.82) for Z0in mm Hg/(L/min). Therefore, Z0is an effective index for determining the CO during TAL attachment in both attachment modes with and without elevated pulmonary vascular resistance.

Pulmonic valve incompetence has been observed during implantation of total artificial lungs (TAL) and may contribute to right ventricular dysfunction in certain attachment modes. The roles of pulmonary system resistance and inertia on valve function were examined retrospectively using data from attachments of a prototype TAL in six pigs. The TAL was attached in parallel and in series with the natural lungs and a hybrid of parallel and series. These conditions lead to varying conditions of resistance and inertia in each animal. The periods of ejection (TE), regurgitation (TR), and sealed valve (TSV), and the regurgitant fraction (Fr) were determined at each condition. The relationships between these variables and the effective pulmonary system resistance (R) and the calculated inertial pressure drop during flow deceleration (PI) were determined. A large Rcreated pulmonic valve incompetence and increased regurgitation, as evidenced by a decreased TSV. A highly negative PIdecreased regurgitation by increasing TE. When R<5 mm Hg/(L/min), Frremained at baseline levels, regardless of other conditions. When R>5 mm Hg/(L/min), the relationship between Fr, R, and PIwas found to be Fr0.014R0.011PI0.15 (R20.82). Thus, pulmonary system resistance should be maintained <5 mm Hg/(L/min) to avoid pulmonic valve incompetence. High device inertance reduced regurgitation but also lead to increased pulmonary system impedances and ventricular work. The design and implementation of a TAL, thus, should focus on having a small effective pulmonary system resistance.

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 0thharmonic 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 C0 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 C0 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 Cfrom 0.52 ± 0.12 at C0 ml/mm Hg to 0.76 ± 0.06 at C5 ml/mm Hg (p< 0.05), but decreased slightly with Cat C> 5 ml/mm Hg. Therefore, the ideal Cfor 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.

The bidirectional Glenn shunt has been successfully applied as an adjunct to ventricular septal defect closure and pulmonary valvulotomy to treat congenitally corrected transposition of the great arteries (ccTGA). The purpose of this study was to examine the volume and pressure unloading effects of the bidirectional Glenn shunt on the hypertrophied pulmonary ventricle in a canine model of ccTGA. Five beagles underwent survival surgery to band the pulmonary artery. Three months later, a polytetrafluoroethylene graft was anastomosed to the superior vena cava and right pulmonary artery. The graft or superior vena cava was clamped to create the normal or bidirectional Glenn circulation, and hemodynamic data were recorded. The bidirectional Glenn shunt significantly reduced right ventricular volume loading and stroke work. Dogs with normal pre-bidirectional Glenn cardiac outputs had greatly reduced right ventricular volumes and pressures with the bidirectional Glenn shunt. Dogs with pre-bidirectional Glenn right ventricular dysfunction had moderate volume but no pressure decreases with the bidirectional Glenn shunt owing to improved left ventricular output. In these dogs it is likely that the decreased level of pressure and volume unloading is because of a concomitant improvement in left ventricular output post-bidirectional Glenn shunt placement. The bidirectional Glenn shunt is effective at unloading the right ventricle in a canine model of ccTGA. Copyright 2003 Elsevier, Inc. All rights reserved.

Pulmonary hypertension (PH) is a challenging disease process to manage. Respiratory and hemodynamic changes that accompany general anesthesia lead to a significant risk of cardiovascular collapse. Certain cases of decompensated PH require extracorporeal membrane oxygenation (ECMO) support as either a bridge to lung transplantation or bridge to recovery. Performing ECMO cannulation without intubation or general anesthesia in these patients may be safer given the severity of their underlying disease process. We present three cases of upper body ECMO cannulation performed on patients with pulmonary hypertension while awake and without mechanical ventilation.

The Tennessee Self-concept Scale was administered to 125 college freshmen. Both scale- and item-level correlation matrices were generated and factored to examine further the construct validity of the test. The scale-level factor analysis resulted in two essentially independent dimensions identified as self-esteem and integration-conflict. While supporting the results of Rentz and White (1967), the dimensions reflected substantially the item-scale overlap which resulted in clusters of spuriously high correlations. An item-level principal component analysis indicated that 23 factors could adequately describe the item interrelationship for the small sample of college students. Under the limitation of the sample size the analysis generated dimensions defined mainly by the column designated external frame of reference classifications; the row designated internal classifications tended not to group together consistently. Summing item responses across rows to generate the three internal frame of reference scores was thus questioned. Correlations between the factors provided no consistent evidence for arbitrarily collapsing factors to generate the test column designated external classifications. Thus, when using the test with similar samples of college freshmen, caution is in order. Further item-level factor analytic studies with larger, more heterogeneous samples are needed.

A patient's capacity for tissue regeneration varies based on age, nutritional status, disease state, lifestyle, and gender. Because regeneration cannot be predicted prior to biomaterial implantation, there is a need for responsive biomaterials with adaptive, personalized degradation profiles to improve regenerative outcomes. This study reports a new approach to use therapeutic ultrasound as a means of altering the degradation profile of silk fibroin biomaterials noninvasively postimplantation. By evaluating changes in weight, porosity, surface morphology, compressive modulus, and chemical structure, it is concluded that therapeutic ultrasound can trigger enhanced degradation of silk fibroin scaffolds noninvasively. By removing microbubbles on the scaffold surface, it is found that acoustic cavitation is the mechanism responsible for changing the degradation profile. This method is proved to be safe for human cells with no negative effects on cell viability or metabolism. Sonication through human skin also effectively triggers scaffold degradation, increasing the clinical relevance of these results. These findings suggest that silk is an ultrasound‐responsive biomaterial, where the degradation profile can be adjusted noninvasively to improve regenerative outcomes. Biomaterials are designed with set degradation profiles. However, some patients require fast degrading biomaterials to avoid an inappropriate immune response and fibrotic capsules; while others require slow degrading biomaterials to enhance cellular and vascular infiltration. Since predicting regenerative rate prior to implantation is currently not possible, this work investigates the use of ultrasound to trigger silk scaffold degradation postimplantation, noninvasively.