John M. Trahanas

Extracorporeal Support for Chronic Obstructive Pulmonary Disease: A Bright Future

In the past the only option for the treatment of respiratory failure due to acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) was invasive mechanical ventilation. In recent decades, the potential for extracorporeal carbon dioxide (CO2) removal has been realized. We review the various types of extracorporeal CO2 removal, outline the optimal use of these therapies for aeCOPD, and make suggestions for future controlled trials. We also describe the advantages and requirements for an ideal long-term ambulatory CO2 removal system for palliation of COPD.

Large Animal Model of Pumpless Arteriovenous Extracorporeal CO2 Removal Using Room Air Via Subclavian Vessels

End-stage lung disease (ESLD) causes progressive hypercapnia and dyspnea and impacts quality of life. Many extracorporeal support (ECS) configurations for CO2 removal resolve symptoms but limit ambulation. An ovine model of pumpless ECS using subclavian vessels was developed to allow for ambulatory support. Vascular grafts were anastomosed to the left subclavian vessels in four healthy sheep. A low-resistance membrane oxygenator was attached in an arteriovenous (AV) configuration. Device function was evaluated in each animal while awake and spontaneously breathing and while mechanically ventilated with hypercapnia induced. Sweep gas (FiO2 = 0.21) to the device was increased from 0 to 15 L/min, and arterial and postdevice blood gases, as well as postdevice air, were sampled. Hemodynamics remained stable with average AV shunt flows of 1.34 ± 0.14 L/min. In awake animals, CO2 removal was 3.4 ± 1.0 ml/kg/min at maximum sweep gas flow. Respiratory rate decreased from 60 ± 25 at baseline to 30 ± 11 breaths per minute. In animals with induced hypercapnia, PaCO2 increased to 73.9 ± 15.1. At maximum sweep gas flow, CO2 removal was 3.4 ± 0.4 ml/kg/min and PaCO2 decreased to 49.1 ± 6.7 mm Hg. Subclavian AV access is effective in lowering PaCO2 and respiratory rate and is potentially an effective ambulatory destination therapy for ESLD patients.

Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts.

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12 hour experiments demonstrated lower potassium (4.3 ± 0.8 vs. 5.0 ± 1.2 mmol/L; p = 0.018) and lactate (3.5 ± 2.8 vs. 4.5 ± 2.9 mmol/L; p = 0.139) levels, and histopathology revealed less tissue damage (p = 0.003) and less weight gain (p = 0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

Treating Lungs: The Scientific Contributions of Dr. Theodor Kolobow.

We are fortunate to live in an age in which biomedical technology has provided us with unprecedented ability to supplant the functions of organs and support the physiologic processes of the human body. Ingenious doctors, physiologists, and engineers helped create these advances with new and innovative ideas. One of these pioneers was Dr. Theodor Kolobow. He is best known for one of his earliest inventions, the spiral coil membrane lung. His contributions to medical innovation, however, are diverse, as he also contributed to advances in hemodialysis, improvements in extracorporeal life support technology/circuit components, and through his laboratory experiments helped shape our current understanding of cardiopulmonary pathophysiology. In retrospect, much of Kolobows work was unified by the theme of preventing iatrogenic lung injury caused by mechanical ventilation. This tenet became more obvious as his later studies progressed to developing techniques and devices intended to limit ventilator pressures, and prevent bacterial colonization of the lungs. Although he formally retired from his research endeavors in 2009, the impact of his contributions remains prominent in our everyday use of techniques and equipment that he either originated or helped to develop.

The Implantable Pediatric Artificial Lung: Interim Report on the Development of an End-Stage Lung Failure Model.

An implantable pediatric artificial lung (PAL) may serve as a bridge to lung transplantation for children with end-stage lung failure (ESLF); however, an animal model of pediatric lung failure is needed to evaluate the efficacy of PAL before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven lambs weighing 20–30 kg underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic dead space fraction (Vd/Vt; baseline = 48.6 ± 5.7%, rPA ligation = 60.1 ± 5.2%, p = 0.012), mean pulmonary arterial pressure (mPPA; baseline = 17.4 ± 2.2 mm Hg, rPA ligation = 28.5 ± 5.2 mm Hg, p < 0.001), and arterial partial pressure of carbon dioxide (baseline = 40.4 ± 9.3 mm Hg, rPA ligation = 57.3 ± 12.7 mm Hg, p = 0.026). Of the seven lambs, three were unable to be weaned from mechanical ventilation postoperatively, three were successfully weaned but suffered cardiorespiratory failure within 4 days, and one survived all 4 days. All four animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA = 28.6 ± 2.2 mm Hg) and remained tachypneic (respiratory rate = 63 ± 21 min−1). Three of the four recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric ESLF and may be suitable for testing and implanting a PAL.

Pediatric Artificial Lung: A Low-Resistance Pumpless Artificial Lung Alleviates an Acute Lamb Model of Increased Right Ventricle Afterload

Lung disease in children often results in pulmonary hypertension and right heart failure. The availability of a pediatric artificial lung (PAL) would open new approaches to the management of these conditions by bridging to recovery in acute disease or transplantation in chronic disease. This study investigates the efficacy of a novel PAL in alleviating an animal model of pulmonary hypertension and increased right ventricle afterload. Five juvenile lambs (20–30 kg) underwent PAL implantation in a pulmonary artery to left atrium configuration. Induction of disease involved temporary, reversible occlusion of the right main pulmonary artery. Hemodynamics, pulmonary vascular input impedance, and right ventricle efficiency were measured under 1) baseline, 2) disease, and 3) disease + PAL conditions. The disease model altered hemodynamics variables in a manner consistent with pulmonary hypertension. Subsequent PAL attachment improved pulmonary artery pressure (p = 0.018), cardiac output (p = 0.050), pulmonary vascular input impedance (Z.0 p = 0.028; Z.1 p = 0.058), and right ventricle efficiency (p = 0.001). The PAL averaged resistance of 2.3 ± 0.8 mm Hg/L/min and blood flow of 1.3 ± 0.6 L/min. This novel low-resistance PAL can alleviate pulmonary hypertension in an acute animal model and demonstrates potential for use as a bridge to lung recovery or transplantation in pediatric patients with significant pulmonary hypertension refractory to medical therapies.

Emergent Transcatheter Aortic Valve Replacement for Aortic Insufficiency

There are few case reports in the literature of transcatheter aortic valve replacement used as emergent therapy for aortic insufficiency. We present a case in which transcatheter aortic valve replacement was implemented successfully as a salvage therapy in a hemodynamically unstable patient having aortic insufficiency as a result of a torn bioprosthetic leaflet during an unrelated abdominal operation. The successful use of this technique in a noncardiac operating room allowed the patient to be placed on extracorporeal support and ultimately to be discharged home.

Normothermic Ex Vivo heart perfusion: Effects of live animal blood and plasma cross circulation

Prolonged normothermic ex vivo heart perfusion could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via normothermic ex vivo heart perfusion. Standard perfusion (SP; n = 40) utilized red blood cell/plasma perfusate and Langendorff technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-blood; n = 6) or cross-circulated filtered plasma (XC-plasma; n = 7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared with 22 of 40 SP hearts (55%; p = 0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3–12. No significant differences were seen between XC-blood and XC-plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478 ± 700 mm Hg/s vs. 872 ± 500; p = 0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

Development of a Model of Pediatric Lung Failure Pathophysiology

A pediatric artificial lung (PAL) is under development as a bridge to transplantation or lung remodeling for children with end-stage lung failure (ESLF). To evaluate the efficiency of a PAL, a disease model mimicking the physiologic derangements of pediatric ESLF is needed. Our previous right pulmonary artery (rPA) ligation model (rPA-LM) achieved that goal, but caused immediate mortality in nearly half of the animals. In this study, we evaluated a new technique of gradual postoperative right pulmonary artery occlusion using a Rummel tourniquet (rPA-RT) in seven (25–40 kg) sheep. This technique created a stable model of ESLF pathophysiology, characterized by high alveolar dead space (58.0% ± 3.8%), pulmonary hypertension (38.4 ± 2.2 mm Hg), tachypnea (79 ± 20 breaths per minute), and intermittent supplemental oxygen requirement. This improvement to our technique provides the necessary physiologic derangements for testing a PAL, whereas avoiding the problem of high immediate perioperative mortality.