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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 L/min at baseline, averaged 6.0 ± 1.0 L/min during the experiment, and was statistically unchanged (p = 0.34). Average arterial oxygen saturation and PCO2 over 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.

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 (Z(0)) was increased by 1, 2.5, and 4 mmHg/(L/min) above baseline. At each Z(0), C was set to 0, 0.34, and 2.1 ml/mmHg. The change in pulmonary system zeroth and first harmonic impedance moduli (ΔZ(0) and ΔZ(1)), the percent change in CO (%ΔCO), and the inlet and outlet anastomoses resistances were calculated for each situation. Results indicate that ΔZ(0) (p < 0.001) but not ΔZ(1) (p = 0.5) had a significant effect on %ΔCO and that %ΔCO = -7.45*ΔZ(0) (R(2) = 0.57). Inlet and outlet anastomoses resistances averaged 0.77 ± 0.16 and 0.10 ± 0.19 mmHg/(L/min), respectively, and the relationship between %ΔCO and TAL resistance, R(T), in mmHg/(L/min) was determined to be %ΔCO = -(7.45f)×(R(T) + 0.87), in which f = the fraction of CO through the TAL. Thus, newer TAL designs can limit %ΔCO to less than 10% if f < 0.75.

Objective: This study evaluated the effectiveness of an atrial septostomy with veno-venous extracorporeal membrane oxygenation in alleviating high afterload right ventricular dysfunction while providing respiratory support. This technique could be applied as a bridge to lung transplantation., Methods: Sheep (56±3 kg) underwent a clamshell thoracotomy and hemodynamic instrumentation, including right ventricular pressure and cardiac output. Sheep with and without tricuspid insufficiency (n=5 each) were examined. While sheep were on extracorporeal membrane oxygenation, right ventricular failure was established by banding the pulmonary artery until cardiac output was 40% to 60% of baseline. An extracardiac atrial shunt was created with modified vascular grafts to examine the effect of shunt flow on hemodynamics. Hemodynamic data were thus collected at baseline, during right ventricular failure, and for 1 hour at 100% (fully open), 70%, 50%, and 30% of baseline shunt flow., Results: Cardiac output was returned to baseline values (tricuspid insufficiency: 5.2±0.2 L/min, without tricuspid insufficiency: 5.3±1.2 L/min) with 100% shunt flow (tricuspid insufficiency: 4.8±1.1 L/min, without tricuspid insufficiency: 4.8±1.0 L/min; P=.15) but remained significantly lower than baseline at 70% to 30% shunt flow. At 100% shunt flow, tricuspid insufficiency shunt flow was 1.4±0.8 L/min and without tricuspid insufficiency shunt flow was 1.7±0.2 L/min. Right ventricular pressure was significantly elevated over baseline values at all shunt flows (P<.001). In the group without tricuspid insufficiency, all sheep died beginning at the 70% shunt condition, whereas all animals with tricuspid insufficiency survived the entire experiment. Normal arterial blood gases were maintained under all conditions., Conclusions: An atrial septostomy accompanied by veno-venous extracorporeal membrane oxygenation is capable of eliminating right ventricular failure while maintaining normal arterial blood gases if sufficient shunt flows are achieved. The presence of tricuspid insufficiency improves the efficacy of the shunt., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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 thoracic artificial lung (TAL) was attached to the pulmonary circulation in a porcine model. Proximal main pulmonary artery (PA) blood flow, in part or whole, was diverted to the TAL, and TAL outlet blood flow was split between the distal main PA and left atrium (LA). The right ventricle (RV) drove blood flow through the combined TAL/natural lung (NL) pulmonary system. Selective banding placed the TAL in parallel with the NLs, in series with the NLs, or in an intermediary hybrid configuration. Parallel TAL attachment lowered pulmonary system impedance, raised cardiac output (CO), and provided the greatest TAL blood flow rate, but reduced the NL blood flow rate which is important for pulmonary embolic clearance and metabolic blood processing. Hybrid or series TAL attachment raised pulmonary system impedance, lowered CO, increased RV oxygen consumption, and reduced RV oxygen supply. Redesign of the PA anastomoses, TAL inlet graft, and TAL entrance and exit would significantly improve hemodynamics and RV function with TAL attachment. Mean LA pressure increased throughout the experiment, which may indicate damage caused by graft attachment to the LA. Pulmonary resistance-flow rate curves may enable clinical prediction of tolerable TAL attachment configurations.

A compliant thoracic artificial lung (TAL) has been developed for acute respiratory failure or as a bridge to transplantation. The development goal was to increase TAL compliance, lower TAL impedance, and improve right ventricular function during use. Prototypes were tested in vitro and in vivo in eight pigs between 67 and 79 kg to determine hemodynamic and gas transfer properties. The in vitro compliance was 16.2 +/- 4.4 ml/mm Hg at pressures < 7.8 mm Hg and 4.3 +/- 1.1 ml/mm Hg above 7.8 mm Hg. In vivo, this compliance significantly reduced blood flow pulsatility from 1.7 at the inlet to 0.36 at the outlet. Device resistance was 1.9 and 1.8 mm Hg/(L/min) at a flow rate of 4 L/min in vitro and in vivo, respectively. Approximately 75% of the resistance was at the inlet and outlet. In vivo TAL O2 and CO2 transfer rates were 188 and 186 ml/min, respectively, at 4 L/min of blood and gas flow, and average outlet O2 saturations exceeded 98% for average flow rates up to and including the maximum tested, 5.3 L/min. The new design has a markedly improved compliance and excellent gas transfer but also possesses inlet and outlet resistances that must be reduced in future designs.

Background: Previous thoracic artificial lungs (TALs) had blood flow impedance greater than that of the natural lungs, which could cause abnormal pulmonary hemodynamics. New compliant TALs (cTALs), however, have an impedance lower than that of the natural lung. Methods: In this study, a cTAL of new design was attached between the pulmonary artery (PA) and the left atrium (LA) in 5 sheep (60.2 ± 1.9 kg). A distal PA band was placed to control the percentage of cardiac output (CO) routed to the cTAL. Rest and exercise conditions were simulated using a continuous dobutamine infusion of 0 and 5 μg/kg/min, respectively. At each dose, a hemodynamic data set was acquired at baseline (no flow to the cTAL), and 60%, 75%, and 90% of CO was shunted to the cTAL. Results: Device resistance did not vary with blood flow rate, averaging 0.51 ± 0.03 mm Hg/(L/min). Under all conditions, CO was not significantly different from baseline. Pulmonary system impedance increased above baseline only with 5 μg/kg/min of dobutamine and 90% of CO diverted to the cTAL. Conclusions: Results indicated minimal changes in pulmonary hemodynamics during PA–LA cTAL attachment for high device flows under rest and exercise conditions. [ABSTRACT FROM AUTHOR]

Background: Right ventricular failure is a major contributor to morbidity and mortality on the lung transplant waiting list. This study was designed to evaluate the effectiveness of an atrial septostomy with venovenous extracorporeal membrane oxygenation (VV-ECMO) as a novel potential bridge to transplantation. Methods: Adult sheep (58 ± 3 kg; n = 12) underwent a clamshell thoracotomy and instrumentation to measure all relevant pressures and cardiac output (CO). Sheep with tricuspid insufficiency (TI [n = 5]) and without tricuspid insufficiency (ØTI [n = 7]) were examined. After creation of a 1-cm atrial septal defect and initiating VV-ECMO, the pulmonary artery (PA) was banded to allow progressive reduction of pulmonary blood flow, and data were collected. Results: The CO in both groups remained unchanged from baseline at all pulmonary blood flow conditions. With TI, the CO was 5.1 ± 1.2 L/min at baseline versus 5.1 ± 1.2 L/min with a fully occluded PA (p = 0.99). For ØTI, the CO was 4.5 ± 1.4 L/min at baseline versus 4.5 ± 1.2 L/min with no pulmonary blood flow (p = 0.99). Furthermore, CO was not affected by the presence of TI (p = 0.76). Mean right ventricular pressures were significantly lower in the TI group (TI = 20.2 ± 11 mm Hg versus ØTI = 29.9 ± 8.9 mm Hg; p < 0.00001). Right and left atrial mean arterial pressures were not different between both groups (p > 0.5). Lastly, VV-ECMO maintained normal blood gases, with mean O2 saturations of 99% ± 4.1% in both groups. Conclusions: Right to left atrial shunting of oxygenated blood with VV-ECMO is capable of maintaining normal systemic hemodynamics and normal arterial blood gases during high right ventricular afterload dysfunction. [Copyright &y& Elsevier]

Background: Pulmonary hypertension and right ventricular failure are major contributors to morbidity and mortality in chronic lung disease. Therefore, large animal models of pulmonary hypertension and right ventricular hypertrophy are needed to study underlying disease mechanisms and test new treatment modalities. The objective of this study was to create a low-mortality model of chronic pulmonary hypertension and right ventricular hypertrophy in sheep. Methods: The vena cavae of nine sheep weighing 62 ± 2 (SEM) kg were injected with 0.375 g of dextran beads (sephadex) every day for 60 d. Pulmonary hemodynamics were assessed via pulmonary artery catheterization prior to the first injection and again on d 14, 28, 35, 42, 49, and 56. At the end of the experiment, the heart was removed, dissected, and weighed to determine the ratio of right ventricular mass to left ventricle plus septal mass (RV:LV+S). Results: All sheep survived to 60 d. The average pulmonary artery pressure rose from 17 ± 1 mmHg at baseline to 35 ± 3 mmHg on d 56 with no significant change in cardiac output (8.7 ± 0.7 to 9.8 ± 0.7 L/min, P = 0.89). The RV:LV+S was significantly higher (0.42 ± 0.01, P < 0.001) than a historic group of untreated normal animals (0.35 ± 0.01, n = 13). Conclusion: This study provides a low-mortality large animal model of moderate chronic pulmonary hypertension and right ventricular hypertrophy. [Copyright &y& Elsevier]