PurposeThe objective of this study was to demonstrate the safety and performance of a unique extracorporeal carbon dioxide removal system (Hemolung, ALung Technologies, Pittsburgh, PA) which incorporates active mixing to improve gas exchange efficiency, reduce exposure of blood to the circuit, and provide partial respiratory support at dialysis-like settings.MethodsAn animal study was conducted using eight domestic crossbred sheep, 6–18 months of age and 49–115 kg in weight. The sheep were sedated and intubated, and a 15.5-Fr dual lumen catheter was inserted into the right jugular vein. The catheter was connected to the extracorporeal circuit primed with heparinized saline, and flow immediately initiated. The animals were then awakened and encouraged to stand. The animals were supported in a stanchion and monitored around the clock. Anticoagulation was maintained with heparin to achieve an aPTT of 46–70 s.ResultsMeasurements included blood flow rate through the device, carbon dioxide exchange rate, pump speed and sweep gas flow rate. Safety and biocompatibility measurements included but were not limited to plasma-free hemoglobin, hematocrit, white blood cell count, platelet count and fibrinogen. The Hemolung removed clinically significant amounts of carbon dioxide, more than 50 ml/min, at low blood flows of 350–450 ml/min, with minimal adverse effects.ConclusionsThe results of 8-day trials in awake and standing sheep supported by the Hemolung demonstrated that this device can consistently achieve clinically relevant levels of carbon dioxide removal without failure and without significant risk of adverse reactions.

There has been growing interest in the mechanobiological function of the aortic valve interstitial cell (AVIC), due to its role in valve tissue homeostasis and remodeling. In a recent study we determined the relation between diastolic loading of the AV leaflet and the resulting AVIC deformation, which was found to be substantial. However, due to the rapid loading time of the AV leaflets during closure (~0.05 s), time-dependent effects may play a role in AVIC deformation during physiological function. In the present study, we explored AVIC viscoelastic behavior using the micropipette aspiration technique. We then modeled the resulting time-length data over the 100 sec test period using a standard linear solid (SLS) model which included Boltzmann superposition. To quantify the degree of creep and stress relaxation during physiological timescales, simulations of micropipette aspiration were preformed with a valve loading time of 0.05 s and a full valve closure time of 0.3 s. The 0.05 s loading simulations suggest that, during valve closure, AVICs act elastically. During diastole, simulations revealed creep (4.65%) and stress relaxation (4.39%) over the 0.3 s physiological timescale. Simulations also indicated that if Boltzmann superposition was not used in parameter estimation, as in much of the micropipette literature, creep and stress relaxation predicted values were nearly doubled (7.92% and 7.35%, respectively). We conclude that while AVIC viscoelastic effects are negligible during valve closure, they likely contribute to the deformation time-history of AVIC deformation during diastole.

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Long term tissue-level durability of the aortic valve (AV) is maintained by the cell populations residing both in the interstitium and on the epithelium. Due to the dynamic environment in which the AV interstitial cells (AVICs) function, recent work has examined the mechano-dependent, biosynthetic and contractile response of these cells [1–4]. Many idealized assumptions have been made about mechanical properties [1, 4], ECM connectivity [2], and deformations that the AVICs undergo during diastole [3]. These assumptions include that the AVICs are elastic, homogenous materials that deformation in an affine sense with the tissue.