Cardiac output during high afterload artificial lung attachment.

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 Z0 from BL, DeltaZ0, and percent change in CO (DeltaCO%) were then calculated to determine their relationship. The DeltaCO% varied significantly with DeltaZ0 (p<10(-40)) and DeltaZ02 (p<10(-4)) but not with the attachment and pulmonary hemodynamics group. The relationship between the variables for all sheep groups was DeltaCO%=0.215DeltaZ0(2)-7.14DeltaZ0+2.94 (R2=0.82) for DeltaZ0 in mm Hg/(L/min). Therefore, Z0 is an effective index for determining the CO during TAL attachment in both attachment modes with and without elevated pulmonary vascular resistance.

Large animal model of chronic pulmonary hypertension.

A large animal model is needed to study artificial lung attachment in a setting simulating chronic lung disease with significant pulmonary hypertension (PH). This study sought to create a sheep model that develops significant PH within 60 days with a low rate of mortality. Sephadex beads were injected in the pulmonary circulation of sheep every other day for 60 days at doses of 0.5, 0.75, and 1 g (n = 10, 10, 7). Mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were obtained every 2 weeks. In the 0.5, 0.75, and 1-g groups, 90, 70, and 14.3% of sheep completed the study, respectively, with the remainder experiencing heart failure. By the 60th day, pulmonary vascular resistance had increased (p < 0.01) from 0.89 +/- 0.3 to 3.2 +/- 0.9 mm Hg/(L/min) and from 0.9 +/- 0.3 to 4.3 +/- 3.2 mm Hg/(L/min) in the 0.5 and 0.75-g groups, respectively. Significant right ventricular hypertrophy was observed in the 0.75-g group but not in the 0.5-g group. Data from the 1-g group were insufficient for analysis due to high mortality. Thus, the 0.5 and 0.75-g groups generate significant PH, but the 0.75-g group is a better model of chronic PH in lung disease due to the development of right ventricular hypertrophy.

Seven-day artificial lung testing in an in-parallel configuration.

BACKGROUND: A thoracic artificial lung, the MC3 Biolung, is being developed as a bridge to lung transplantation or as a treatment for acute respiratory insufficiency. METHODS: The thoracic artificial lung was tested in 10 sheep with the goal of 7 days of respiratory support. The sheep were recovered from surgery and monitored awake for 7 days. Hemodynamics, blood gases, blood cell counts, and organ function were recorded, and after 7 days, all sheep were euthanized and necropsied. RESULTS: Seven sheep survived the full duration. Cardiac output and mean arterial blood pressure were unchanged, averaging 4.7 +/- 0.8 L/min and 98 +/- 10 mm Hg, respectively. Arterial oxygen tension and device oxygen transfer rate were also unchanged, averaging 110 +/- 26 mm Hg and 97.7 +/- 35 mL/min, respectively. Arterial carbon dioxide tension was within normal ranges during the entire experiment, averaging 37.4 +/- 3.8 mm Hg. Artificial lung blood flow decreased from 51% +/- 14% of cardiac output on day 1 to 30% +/- 16% by day 7 because of changes in natural and artificial lung resistance. White blood cell counts were significantly elevated on days 5 and 7, and lastly, kidney and liver function remained normal, although signs of kidney infarction or hemorrhage were noted. CONCLUSIONS: The thoracic artificial lung is suitable for 7-day attachment, but improvements in blood biocompatibility are warranted.

Improving Blood Compatibility of Intravascular Oxygen Sensors Via Catalytic Decomposition of S-Nitrosothiols to Generate Nitric Oxide In Situ.

Reliable, real-time, in vivo sensing (intravascular) of blood gases and electrolytes remains a difficult challenge owing to biocompatibility issues that occur when chemical sensors are implanted into the blood stream. Recently, local release of nitric oxide (NO) at the sensor/blood interface has been suggested as a potential solution to this problem. However, the lifetime of NO release from thin polymer films coated on implanted sensors is limited by the reservoir of NO donor loaded within the polymeric coating. To continuously produce NO at the sensor/blood interface, a novel approach to catalytically decompose endogenous S-nitrosothiols (RSNOs) in blood to generate NO in situ is reported herein. Metallic copper particles of two different sizes (3 µm and 80 nm) are embedded as catalysts in thin polymer coatings on the surface intravascular electrochemical oxygen sensing catheters. Oxygen levels (partial pressure of oxygen; PO(2)) provided by the copper particle/polymer coated sensors are, on average, more accurate than values obtained from non-NO generating control sensors when both types of sensors are implanted in porcine arteries for 19-20 h. Upon termination of each in vivo study, catheters were explanted and examined for surface thrombosis via both visual image and lactate dehydrogenase (LDH) assay. The results indicate that the Cu(0)-catalyst coatings significantly reduce the occurrence of surface thrombosis, likely from the ability to generate NO from endogenous RSNO species at the sensor/blood interface.

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 0 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 > or = 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 > or = 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.

A polymethylpentene fiber gas exchanger for long-term extracorporeal life support.

A polymethylpentene (PMP) fiber gas exchange device was evaluated in healthy sheep (35-42 kg) to characterize its performance and potential use in clinical extracorporeal life support (ECLS). Five PMP devices (1.3 m2) were compared with five silicone rubber membrane lung (SRML) devices (1.5 m2) that were supported on venovenous ECLS for 72 hours. The two device groups were compared for differences in gas exchange, device pressure gradient, hematology, blood biochemistry, and pathology. The results showed superiority in the PMP devices in both oxygen and CO2 exchange when compared at similar blood flow rates. Platelet consumption and the device pressure gradient were significantly less when using the PMP device. The device pressure gradient across the PMP devices was < 20 mm Hg as compared with > 150 mm Hg for the SRML devices at all blood flow rates. Changes in plasma hemoglobin levels, leukocyte counts, blood chemistry results, and pathologic findings were not significantly different between the two device groups. Plasma leakage or device failure did not occur in any of the test devices. These data support the use of the PMP device for extended circulatory support. Patients may fare better because of improved preservation of platelets, and the low resistance may allow for wider use of centrifugal-style pumps or the use of the device in a pumpless arteriovenous mode.