A novel electrochemically controlled release method for nitric oxide (NO) (based on electrochemical reduction of nitrite ions) is combined with an amperometric oxygen sensor within a dual lumen catheter configuration for the continuous in vivo sensing of the partial pressure of oxygen (PO2) in blood. The on-demand electrochemical NO generation/release method is shown to be fully compatible with amperometric PO2 sensing. The performance of the sensors is evaluated in rabbit veins and pig arteries for 7 and 21 h, respectively. Overall, the NO releasing sensors measure both venous and arterial PO2 values more accurately with an average deviation of −2 ± 11% and good correlation (R2 = 0.97) with in vitro blood measurements, whereas the corresponding control sensors without NO release show an average deviation of −31 ± 28% and poor correlation (R2 = 0.43) at time points >4 h after implantation in veins and >6 h in arteries. The NO releasing sensors induce less thrombus formation on the catheter surface in both veins and arteries (p < 0.05). This electrochemical NO generation/release method could offer a new and attractive means to improve the biocompatibility and performance of implantable chemical sensors.

Purpose An artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that using a veno-venous extracorporeal life support (VV-ECLS) artificial placenta after ventilatory failure would stabilize premature lambs and maintain normal fetal physiologic parameters for 70h. Methods A near-term neonatal lamb model (130 days; term=145) was used. The right jugular vein (drainage) and umbilical vein (reinfusion) were cannulated with 10–12 Fr cannulas. Lambs were then transitioned to an infant ventilator. After respiratory failure, the endotracheal tube was filled with amniotic fluid, and VV-ECLS total artificial placenta support (TAPS) was initiated. Lambs were maintained on TAPS for 70h. Results Six of seven lambs survived for 70h. Mean ventilation time was 57±22min. During ventilation, mean MAP was 51±14mmHg, compared to 44±14mmHg during TAPS (p=0.001). Mean pH and lactate during ventilation were 7.06±0.15 and 5.7±2.3mmol/L, compared to 7.33±0.07 and 2.0±1.8mmol/L during TAPS (p<0.001 for both). pO2 and pCO2 remained within normal fetal parameters during TAPS, and mean carotid blood flow was 25±7.5mL/kg/min. Necropsy showed a patent ductus arteriosus and no intracranial hemorrhage in all animals. Conclusions The artificial placenta stabilized premature lambs after ventilatory failure and maintained fetal circulation, hemodynamic stability, gas exchange, and cerebral perfusion for 70h.

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long-term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS-DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS-DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4-6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min ± 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min ± 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD-30 (6.8 mL/h ± 1.7). DCD-30 had lower CrCl (0.9 mL/min ± 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.

Artificial lungs have been used in the clinic for multiple decades to supplement patient pulmonary function. Recently, small-scale microfluidic artificial lungs (μAL) have been demonstrated with large surface area to blood volume ratios, biomimetic blood flow paths, and pressure drops compatible with pumpless operation. Initial small-scale microfluidic devices with blood flow rates in the l/min to ml/min range have exhibited excellent gas transfer efficiencies; however, current manufacturing techniques may not be suitable for scaling up to human applications. Here, we present a new manufacturing technology for a microfluidic artificial lung in which the structure is assembled via a continuous "rolling" and bonding procedure from a single, patterned layer of polydimethyl siloxane (PDMS). This method is demonstrated in a small-scale four-layer device, but is expected to easily scale to larger area devices. The presented devices have a biomimetic branching blood flow network, 10m tall artificial capillaries, and a 66 m thick gas transfer membrane. Gas transfer efficiency in blood was evaluated over a range of blood flow rates (0.1-1.25 ml/min) for two different sweep gases (pure O, atmospheric air). The achieved gas transfer data closely follow predicted theoretical values for oxygenation and CO removal, while pressure drop is marginally higher than predicted. This work is the first step in developing a scalable method for creating large area microfluidic artificial lungs. Although designed for microfluidic artificial lungs, the presented technique is expected to result in the first manufacturing method capable of simply and easily creating large area microfluidic devices from PDMS.

Semi-crystalline thermoplastics are an important class of biomaterials with applications in creating extracorporeal and implantable medical devices. In situ release of nitric oxide (NO) from medical devices can enhance their performance via NO’s potent anti-thrombotic, bactericidal, anti-inflammatory, and angiogenic activity. However, NO-releasing semi-crystalline thermoplastic systems are limited and the relationship between polymer crystallinity and NO release profile is unknown. In this paper, the functionalization of poly(ether-block-amide) (PEBA), Nylon 12, and polyurethane tubes, as examples of semi-crystalline polymers, with the NO donor S-nitroso-N-acetylpenicillamine (SNAP) is demonstrated via a polymer swelling method. The degree of crystallinity of the polymer plays a crucial role in both SNAP impregnation and NO release. Nylon 12, which has a relatively high degree of crystallinity, exhibits an unprecedented NO release duration of over 5 months in a low NO level, while PEBA tubing exhibits NO release over days to weeks. As a new biomedical application of NO, the NO-releasing PEBA tubing is examined as a cannula for continuous subcutaneous insulin infusion. The released NO is shown to enhance insulin absorption into the bloodstream probably by suppressing the tissue inflammatory response, and thereby benefit insulin pump therapy for diabetes management.

An extracorporeal artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that a venovenous extracorporeal life support (VV-ECLS) artificial placenta would maintain fetal circulation, hemodynamic stability, and adequate gas exchange for 24 hours. A near-term neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors, average mean arterial pressure was 69 ± 10 mm Hg for the first 4 hours and 36 ± 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 ± 30. Mean VV-ECLS flow was 94 ± 20 ml/kg/min. Using a gas mixture of 50% O(2)/3% CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 ± 0.09, with Po(2) of 35 ± 12 mm Hg and Pco(2) of 48 ± 12 mm Hg. Necropsy revealed a patent ductus arteriosus in all cases, and there was no gross or microscopic intracranial hemorrhage. Complications in failed attempts included technically difficult cannulation and multisystem organ failure. Future studies will enhance stability and address the factors necessary for long-term support.

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Background Centrifugal pumps are increasingly used for temporary mechanical support for the treatment of cardiogenic shock. However, centrifugal pumps can generate excessive negative pressure and are afterload-sensitive. A previously developed modified roller pump mitigates these limitations both in vitro and in preliminary animal experiments. We report the results of intermediate-term testing of our evolving pump technology, known as BioVAD. Methods The BioVAD was implanted in 6 adult male sheep (62.5 ± 3.9 kg), with drainage from the left atrium and reinfusion into the descending aorta. The sheep were monitored for 5 days. Heparin was given during the initial implantation, but no additional anti-coagulation was given. Data collected included hemodynamic status, pump flow and pressures, laboratory values to monitor end-organ function and hemolysis, pathologic specimens to evaluate for thromboembolic events and organ ischemia, and explanted pump evaluation. Results All animals survived the planned experimental duration and there were no pump malfunctions. Mean BioVAD flow was 3.57 ± 0.30 L/min (57.1 cc/kg/min) and mean inlet pressure was -30.51 ± 4.25 mmHg. Laboratory values, including plasma free hemoglobin, creatinine, lactate, and bilirubin levels, remained normal. Three animals had small renal cortical infarcts, but there were no additional thromboembolic events or other abnormalities seen on pathologic examination. No thrombus was identified in the BioVAD blood flow path. Conclusions The BioVAD performed well for five days in this animal model of temporary left ventricular assistance. Its potential advantages over centrifugal pumps may make it applicable for short-term mechanical circulatory support.