Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure was <15 mm Hg during ECS. During the lung assessment period, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.

Performance of a MedArray silicone hollow fiber oxygenator.

A silicone hollow fiber oxygenator was evaluated to characterize gas transfer and biocompatibility. The device's fiber bundle was composed of MedArray's silicone hollow fibers with a 320 microm outside diameter, a 50 microm wall thickness, a surface area of 0.45 m, and a 0.49 void fraction. An in vitro gas exchange study was performed comparing the MedArray device (n = 9) with the Medtronic 0600 oxygenator (n = 6) using Association for the Advancement of Medical Instrumentation standards and blood flow rates of 0.5-1.75 L/min, and an oxygen to blood flow ratio of two. Biocompatibility and resistance studies were performed in vivo using a swine venovenous extracorporeal membrane oxygenation model (MedArray n = 5, Medtronic n = 5). Average O(2) transfer at 1 L/min was 86 ml/min/m in the MedArray device and 101.1 ml/min/m in the Medtronic device. At 0.5 L/min the MedArray and Medtronic device average resistance was 15.5 and 148.5 mm Hg/(L/min), respectively. Both devices had similar platelet consumption and hemolysis. Results indicate that the MedArray device has lower O(2) transfer efficiency, similar biocompatibility, and lower resistance than the Medtronic 0600 oxygenator. Optimization of the MedArray fiber bundle and housing design is necessary to improve O(2) transfer efficiency while maintaining lower device resistance than the Medtronic oxygenator.

Effect of varying nitric oxide release to prevent platelet consumption and preserve platelet function in an in vivo model of extracorporeal circulation.

The gold standard for anticoagulation during extracorporeal circulation (ECC) remains systemic heparinization and the concomitant risk of bleeding in an already critically ill patient could lead to death. Normal endothelium is a unique surface that prevents thrombosis by the release of antiplatelet and antithrombin agents. Nitric oxide (NO) is one of the most potent, reversible antiplatelet agents released from the endothelium. Nitric oxide released from within a polymer matrix has been proven effective for preventing platelet activation and adhesion onto extracorporeal circuits. However, the critical NO release (NO flux) threshold for thrombus prevention during ECC has not yet been determined. Using a 4-hour arteriovenous (AV) rabbit model of ECC, we sought to find this threshold value for ECC circuits, using an improved NO-releasing coating (Norel-b). Four groups of animals were tested at variable NO flux levels. Hourly blood samples were obtained for measurement of arterial blood gases, platelet counts, fibrinogen levels and platelet function (via aggregometry). A custom-built AV circuit was constructed with 36 cm of poly(vinyl)chloride (PVC) tubing, a 14 gauge (GA) angiocatheter for arterial access and a modified 10 French (Fr) thoracic catheter for venous access. The Norel-b coating reduced platelet activation and thrombus formation, and preserved platelet function - in all circuits that exhibited an NO flux of 13.65 x 10(10) mol x cm(-2) x min(-1). These results were significant when compared with the controls. With the Norel-b coating, the NO flux from the extracorporeal circuit surface can be precisely controlled by the composition of the polymer coating used, and such coatings are shown to prevent platelet consumption and thrombus formation while preserving platelet function in the animal.

Thirty-day in-parallel artificial lung testing in sheep.

BACKGROUND: Thirty-day testing of the MC3 Biolung (MC3 Inc, Ann Arbor, MI) total artificial lung (TAL) was performed to prepare for future clinical testing. METHODS: TAL inlet and outlet grafts were sewn to the pulmonary artery and left atrium of 8 sheep (35.6 +/- 1.6 kg), and the TAL was attached the next day. Hemodynamic and sheep blood gas data were measured every 1 to 4 hours. TAL blood gases were measured twice daily, and organ function was assessed three times per week. The TAL was replaced if its resistance increased 300% or if the oxygen content difference across the TAL decreased 25% versus baseline. After 30 days, the sheep were euthanized and necropsied. RESULTS: Five sheep survived 30 days. Three sheep were euthanized before 30 days due to bleeding, mechanical graft failure, or gastric distress. Survivors had normal, stable hemodynamics and blood gases. Average device use was 9.5 +/- 2.1 days. TAL oxygen transfer was 108 +/- 9.2 mL/min with 51% +/- 6.3% of cardiac output flowing to the TAL. TAL resistance and flow were 1.3 +/- 0.3 mm Hg x min/L and 2.4 +/- 0.2 L/min at baseline versus 2.6 +/- 0.9 mm Hg x min/L and 2.0 +/- 0.2 L/min for the remaining 30 days. Platelet and white blood cell counts increased 88% and 84% from baseline, respectively, after 10 days and were stable thereafter. Ischemic lesions in the kidney were seen in most sheep at necropsy, but organ function was normal. CONCLUSIONS: Thirty-day respiratory support was feasible with the Biolung, but improvements in biocompatibility and anticoagulation regimen are warranted to reduce the thrombogenicity of the device.

An in vitro method for assessing biomaterial-associated platelet activation.

The development of a nonthrombogenic artificial surface for use with indwelling sensors or catheters remains an elusive goal despite decades of ongoing research. In vivo studies are both labor intensive and costly, and are therefore an inefficient way to rapidly screen possible surface materials. The following in vitro model used glass, polyvinyl chloride (PVC), and polypropylene test tubes incubated with 111In-labeled rabbit platelets and illustrated that, despite equivalent platelet count and function, platelet adhesion was greatest on glass (n = 13), with PVC (n = 17) at 67 +/- 8% and polypropylene (n = 13) at 43 +/- 5% when compared with glass. Extrapolating this method by coating test tubes with new, nonthrombogenic materials is a quick and reliable way to screen material before embarking upon more lengthy in vivo animal studies.