Grant W. Griffith

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.

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.

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.

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, &Dgr;Z0, and percent change in CO (&Dgr;CO%) were then calculated to determine their relationship. The &Dgr;CO% varied significantly with &Dgr;Z0 (p < 10−40) and &Dgr;Z02 (p < 10−4) but not with the attachment and pulmonary hemodynamics group. The relationship between the variables for all sheep groups was &Dgr;CO% = 0.215&Dgr;Z02 − 7.14&Dgr;Z0 + 2.94 (R2 = 0.82) for &Dgr;Z0 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.

Hematological changes during short-term tidal flow extracorporeal life support

Various methods exist in the clinical practice of long-term venovenous (VV) extracorporeal life support (ECLS). Among the clinical techniques used are single venous access with a dual-lumen catheter, and cannulation of the jugular and femoral veins. Tidal flow VV ECLS uses a single-lumen catheter to achieve both venous drainage and arterialized reinfusion through a series of tubing occluders that are automated by a pump. A single venous occluder tidal flow system with a 15 Fr single-lumen cannula (n- 6) and passive filling M pump was compared to a conventional 14 Fr dual-lumen cannula (n- 7) and roller pump for four hours of VV ECLS. The changes in platelet count and plasma-free hemoglobin (pHgb) were compared. The results showed a decline in platelet counts typical of ECLS in both groups that were not significantly different from each other. A small elevation in pHgb did not rise above normal clinical levels of 15 mg/dL in either group after four hours of ECLS. Some recirculation was observed and needs to be addressed in future studies. Single occluder tidal flow ECLS may be feasible and efficacious for long-term application once recirculation is resolved and the system evaluated for long-term support.