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Objective Upper airway malacia highly complicates the treatment of benign laryngotracheal stenosis, and no ideal option is available to date. We here explore the use of extraluminal biodegradable splints in an animal model of long-segment anterior tracheomalacia (TM). We show the efficacy, as well as the tissue tolerance, of a custom-made biodegradable extraluminal device surgically inserted around the trachea. Study Design Preclinical animal study. Methods Anterior TM was induced in rabbits through an anterior neck approach by removing eight consecutive anterior tracheal rings without damaging the underlying mucosa. Malacia was corrected during the same surgery by pexy sutures, suspending the tracheal mucosa to an experimental biodegradable device. Symptoms, survival, and tissue reaction were compared to healthy and sham surgery controls. Results The model induced death by respiratory failure within minutes. Ten animals received the experimental treatment, and those who survived the perioperative period remained asymptomatic with a maximum follow-up of 221 days. Histological studies at programmed euthanasia showed complete degradation of the prosthesis, with significant remnant fibrosis around the trachea. However, the tracheal stiffness of test segments was comparatively less than that of control segments. Conclusion Extraluminal biodegradable splints rescued animals with a condition otherwise incompatible with life. It was well tolerated, leaving peritracheal fibrosis that was not as stiff as normal trachea. The external tracheal stiffening was sufficient for the test animals to live through the phase of severe acute hypercollapsibility. This represents a valid option to help pediatric patients with laryngotracheal stenosis and associated cartilaginous airway malacia. Level of Evidence NA. Laryngoscope, 2017

OBJECTIVES The aim was to determine 3-dimensional (3D) geometrical deformation of the aortic root (AoR) following the David procedure in order to evaluate local haemodynamical conditions of individual AoR elements. METHODS In the experimental set-up, the David procedure was performed on 10 domestic pigs. Data were compared with the measurements obtained in 10 native AoRs. In each AoR, six high-resolution ultrasonometric crystals (200 Hz) were implanted, being positioned at each commissure and at the AoR base. 3D geometrical deformation of the AoR, torsion and tilt angle was determined. Computed fluid dynamics (CFD) simulation analysis was used to evaluate local pressure, flow and shear stress. RESULTS In David AoRs, the tilt angle was maximal at a peak ejection of 25.9 ± 1.49° and minimal at the end of isovolemic contraction at 23.5 ± 0.80°. David root rotation was maximal at a peak ejection of 27.93 ± 1.54° and minimal at the end of the isovolemic contraction at 25.7 ± 1.32°. In the native AoR, the opposite was observed. Here, the tilt and rotation angle were maximal at the end of isovolemic contraction (17.25 ± 0.68° and 19.71 ± 0.73°) and decreased to its minimal values at peak ejections (14.1 ± 0.62° and 16.33 ± 0.47°). In David AoR, high pressure (>140 mmHg) combined with low-to-moderate shear stress (0-40 Pa) was found at the leaflet body from the beginning of isovolemic contraction till the opening of the aortic valve. Similar high pressure (>140 mmHg) and shear stress (0-40 Pa) were found in the period from aortic valve closure till the beginning of the isovolemic contraction. In native AoRs, high pressure (>95 mmHg) was conjoined with low-to-moderate shear stress (0-30 Pa) at the leaflets and was registered at the end of isovolemic contraction. CONCLUSIONS The David AoR is haemodynamically less favourable when compared with the native AoR. During almost two-thirds of the time period of the cardiac cycle, AoR elements are exposed to high pressure and low shear stress. In contrast, in native AoRs, similar conditions were present only during the short period of isovolemic contraction.

Purpose: Previous studies using FLASH radiotherapy (RT) in mice showed a marked increase of the differential effect between normal tissue and tumors. To stimulate clinical transfer, we evaluated whether this effect could also occur in higher mammals. Experimental Design: Pig skin was used to investigate a potential difference in toxicity between irradiation delivered at an ultrahigh dose rate called “FLASH-RT” and irradiation delivered at a conventional dose rate called “Conv-RT.” A clinical, phase I, single-dose escalation trial (25–41 Gy) was performed in 6 cat patients with locally advanced T2/T3N0M0 squamous cell carcinoma of the nasal planum to determine the maximal tolerated dose and progression-free survival (PFS) of single-dose FLASH-RT. Results: Using, respectively, depilation and fibronecrosis as acute and late endpoints, a protective effect of FLASH-RT was observed (≥20% dose-equivalent difference vs. Conv-RT). Three cats experienced no acute toxicity, whereas 3 exhibited moderate/mild transient mucositis, and all cats had depilation. With a median follow-up of 13.5 months, the PFS at 16 months was 84%. Conclusions: Our results confirmed the potential advantage of FLASH-RT and provide a strong rationale for further evaluating FLASH-RT in human patients. See related commentary by Harrington, p. 3

In extreme situations such as hyperacute rejection of heart transplant or major heart trauma, heart explantation and extracorporeal membrane oxygenation (ECMO) hemodynamic support might be the only means for survival. In our previous model of acardia, pulmonary artery (PA) was clamped and did not receive any anterograde blood flow. A model of anterograde PA perfusion might be necessary to avoid ischemic pulmonary damage in prolonged ECMO in acardia. The aim of this study was to describe the surgical technique and to determine the feasibility of an anterograde lung perfusion in acardia through the anastomosis of the right internal mammary artery (RIMA) to the PA. A venoarterial cardiopulmonary bypass was established in three pigs (72 ± 2.6 kg) by the transjugular insertion to the caval axis of a double-staged cannula with carotid artery return. Heart was excised and ECMO was established as previously reported. Right internal mammary artery was harvested and after measurement of its output (93.3 ± 5.8 ml/min, representing 2.17% ± 0.15% of total pump flow), it was anastomosed to PA. Right internal mammary artery anastomosis to PA is a feasible, safe, and easy to perform maneuver assuring an anterograde lung perfusion in acardia.

Fibrin glue products and collagen patches are frequently used as a sealing product, preventing surgical side bleedings. This is especially true in the field of cardiovascular surgery, where increasing numbers of patients are being operated with antiplatelet and anticoagulation therapy. The aim of this report was, in an in vitro hemodynamic setting, to examine the sealant properties of the TachoSil (Nycomed Pharma, Linz, Austria) patch. Burst pressure and normal force of 15 TachoSil sealed defects were measured. This was determined in a closed hydraulic system. Mean burst pressure load for a 5-mm defect was 69+/-11.4 mmHg; for a 7-mm defect was 63+/-16 mmHg; and, 62+/-16 mmHg for the defect with a diameter of 10 mm (P>0.05). The mean calculated normal force was as follows: 0.91+/-0.15 N for the 5 mm defect, 6.5+/-1.6 N for the 7 mm, and 8.1+/-0.75 N for the 10 mm defect. The TachoSil patch has the capability to seal small defects. However, at the larger defects the seal character was significantly reduced. These results suggest that the device may be a good alternative for hemostasis for small defects. The capacity to curtail or stop hemorrhage at the larger defects is unlikely.

Background High-molecular-weight, low-substituted hydroxyethyl starch (HES) may not affect blood coagulation more than low-molecular-weight, low-substituted HES. The authors assessed in vivo the effect of a lowered C2/C6 ratio on pharmacokinetic characteristics and the impact on blood coagulation of high-molecular-weight, low-substituted HES. Methods A prospective, randomized, parallel study in 30 pigs compared HES 650/0.42/2.8 with HES 650/0.42/5.6. Before, during, and after infusion of 30 ml/kg body weight HES, blood samples were collected over 630 min to measure HES concentrations and plasmatic coagulation and to assess blood coagulation in whole blood by Thrombelastography (TEG; Haemoscope Corporation, Niles, IL). Pharmacokinetic parameters were estimated using a two-compartment model. Results The elimination constant was 0.009 +/- 0.001 min(-1) for HES 650/0.42/2.8 and 0.007 +/- 0.001 min(-1) for HES 650/0.42/5.6 (P < 0.001); the area under the plasma concentration-time curve was 1,374 +/- 340 min x g/l for HES 650/0.42/2.8 and 1,697 +/- 411 min x g/l for HES 650/0.42/5.6 (P = 0.026). The measured plasma HES concentrations were not different between HES 650/0.42/2.8 and HES 650/0.42/5.6. Both HES solutions equally affected blood coagulation: Thrombelastographic coagulation index decreased similarly at the end of infusion of HES 650/0.42/2.8 and at the end of infusion of HES 650/0.42/5.6 (P = 0.293). Also, activated partial thromboplastin and prothrombin times increased similarly for HES 650/0.42/2.8 and HES 650/0.42/5.6 (P = 0.831). Conclusion Reducing the C2/C6 ratio in high-molecular, low-substituted HES solutions results in a slightly faster HES elimination. However, the blood coagulation compromising effect was unaffected.

Background Hydroxyethyl starches (HES) with lower impact on blood coagulation but longer intravascular persistence are of clinical interest. The current study aimed to investigate in vivo the isolated effect of molecular weight on blood coagulation during progressive acute normovolemic hemodilution. Methods Twenty-four pigs were normovolemically hemodiluted up to a total exchange of 50 ml . kg . body weight of HES 650/0.42 or HES 130/0.42. Serial blood sampling was performed to measure HES plasma concentration and to assess blood coagulation. Concentration-effect relations were analyzed by linear regression, followed by the Student t test on regression parameters. Results Blood coagulation was increasingly compromised toward hypocoagulability by acute normovolemic hemodilution with both treatments (P < 0.01). Significantly greater impact on activated partial thromboplastin time (P = 0.04) and significantly stronger decrease of maximal amplitude (P = 0.04), angle alpha (P = 0.02), and coagulation index (P = 0.02) was seen after acute normovolemic hemodilution with HES 650/0.42 as compared with HES 130/0.42. Except for factor VIII (P = 0.04), no significant differences between both treatments were observed when relating antihemostatic effects to HES plasma concentrations (P > 0.05). A significantly lesser decrease of hemoglobin concentration has been found with HES 650/0.42 as compared with HES 130/0.42 (P < 0.01) in relation to HES plasma concentrations. Conclusion High-molecular-weight HES (650/0.42) shows a moderately greater antihemostatic effect than low-molecular-weight HES (130/0.42) during acute normovolemic hemodilution. However, similar effects on hemostasis were observed with both treatments when observed antihemostatic effects were related to measured HES plasma concentrations. In addition, HES 650/0.42 may have a lower efficacy in immediately restoring plasma volume.

OBJECTIVES: The reconstruction of the right ventricular outflow tract (RVOT) with valved conduits remains a challenge. The reoperation rate at 5 years can be as high as 25% and depends on age, type of conduit, conduit diameter and principal heart malformation. The aim of this study is to provide a bench model with computer fluid dynamics to analyse the haemodynamics of the RVOT, pulmonary artery, its bifurcation, and left and right pulmonary arteries that in the future may serve as a tool for analysis and prediction of outcome following RVOT reconstruction. METHODS: Pressure, flow and diameter at the RVOT, pulmonary artery, bifurcation of the pulmonary artery, and left and right pulmonary arteries were measured in five normal pigs with a mean weight of 24.6 ± 0.89 kg. Data obtained were used for a 3D computer fluiddynamics simulation of flow conditions, focusing on the pressure, flow and shear stress profile of the pulmonary trunk to the level of the left and right pulmonary arteries. RESULTS: Three inlet steady flow profiles were obtained at 0.2, 0.29 and 0.36 m/s that correspond to the flow rates of 1.5, 2.0 and 2.5 l/min flow at the RVOT. The flow velocity profile was constant at the RVOT down to the bifurcation and decreased at the left and right pulmonary arteries. In all three inlet velocity profiles, low sheer stress and low-velocity areas were detected along the left wall of the pulmonary artery, at the pulmonary artery bifurcation and at the ostia of both pulmonary arteries. CONCLUSIONS: This computed fluid real-time model provides us with a realistic picture of fluid dynamics in the pulmonary tract area. Deep shear stress areas correspond to a turbulent flow profile that is a predictive factor for the development of vessel wall arteriosclerosis. We believe that this bench model may be a useful tool for further evaluation of RVOT pathology following surgical reconstructions.

Coating of cardiopulmonary bypass circuits may be a solution to prevent adverse effects induced by contact of blood elements with foreign surfaces. Using an animal model, we investigated the Trillium™ coating of cardiopulmonary bypass circuits (a new process involving polyethylene oxide, sulphonate groups and heparin) at low systemic heparinization, focusing on haemolysis and clot formation. Cardiopulmonary bypass was initiated through jugulo-carotid acess with ACT maintained around 180 sec. Treated circuits (Trillium group) were evaluated in 3 calves (mean weight of 66.0±8.7 kg), vs. untreated circuits in 3 control calves (mean weight of 60.7±7.5 kg). Blood samples were drawn at regular intervals for biochemical, hematological and blood gas analyses. After 6 consecutive hours, the animals were weaned from CPB and were awakened. The circuits were analyzed for clot deposits. After 7 days the animals were sacrificed and an autopsy was carried out. Red cell and white cell counts did not change over the 6 hours. Platelet counts dropped to 75.9±7.3% of the baseline value in the Trillium group after 6 hours whereas counts dropped to 57.2±26.0 in the control group (p

Une membrane biorésorbable, composée de polysaccharides (hyaluronate de sodium et carboxymethylcellulose), a déjà été employée avec succès dans la prévention des adhérences péritonéales. Son efficacité dans la prévention des adhérences péricardiques est testée. Deux groupes de six porcs chacun (poids moyen 72 +/- 8kg) ont été choisis pour l'expérience. Dans le groupe "membrane", après l'excision d'une partie du péricarde, la région du ventricule gauche exposée est divisée en deux aires: l'aire A où six points de Prolène sont suturés et l'aire B laissée intacte. La membrane est appliquée sur ces deux aires ainsi que sur les régions adjacentes recouvertes de péricarde (aire C). Dans le groupe "contrôle", la même intervention est effectuée, mais sans membrane. Les animaux sont sacrifiés un mois plus tard. Le status adhérentiel des différentes aires ainsi que la visibilité des vaisseaux épicardiques sont évalués au moyen d'échelles de sévérité allant de 0 à 3 pour les adhérences et de 0 à 2 pour la visibilité. La différence entre les 2 groupes est considérée comme significative si p < 0.05. Le score d'adhérence de l'aire A est de 1.7 +/- 0.5 dans le groupe membrane versus 2.5 +/- 0.5 dans le groupe contrôle (p = 0.02) et le score de visibilité est de 1.3 +/- 0.8 versus 2 +/- 0 respectivement (n.s.). Pour l'aire B, le score d'adhérence est de 1 +/- 0 dans le groupe membrane versus 2 +/- 0.6 dans le groupe contrôle (p = 0.03) et le score de visibilité est de 0.7 +/- 0.5 versus 2 +/- 0 respectivement (p = 0.001). Enfin pour l'aire C, le score d'adhérence est de 1 +/- 0 dans les deux groupes et le score de visibilité est de 0.7 +/- 0.4 dans le groupe membrane versus 0.5 +/- 0.5 dans le groupe contrôle (n.s.). Dans ce modèle animal, le rôle de la membrane biorésorbable dans la prévention des adhérences péricardiques se limite aux régions non recouvertes de péricarde et dépourvues de matériel étranger. La présence de corps étranger neutralise son effet.

Despite an overall improvement in cardiopulmonary bypass (CPB) technology and materials, air emboli still occur. The latest generation membrane oxygenator from Bentley Laboratories, the SpiralGold™, was tested ex vivo for its air handling ability. The study was conducted on four calves. Bolus amounts of air of 10, 15 and 20 cm3 were each injected three times, upstream of the oxygenator and a bubble detector located directly downstream. The amount of bubbles was measured semiquantitatively on a 10 unit scale (U = one semiquantitative unit). The animals were killed 10 days after the CPB. When 10 cm3 of air was injected, no bubbles were detected. With 15 and 20 cm3, respectively, 1 ± 1.5 and 5 ± 3.3 U of bubbles were detected. Despite a total of 135 cm3 of air injected as large bolus amounts, all the animals survived without any obvious neurological deficit secondary to air bubble manipulation. In conclusion, the Spiral Gold™ oxygenator per se can reliably trap an air bolus of up to 10 cm3. This feature should be taken into account when choosing an oxygenator, as it offers an additional barrier to air bubbles in the CPB circuit.

Objectives The aim was to evaluate the impact of the aortic valve reimplantation (David) and of the aortic root (AoR) remodelling (Yacoub) on the AoR haemodynamics. Methods In an experimental setup where the clinical scenario of Yacoub, ( n = 5, domestic pig) and of David ( n = 5, domestic pig) procedure was performed in each AoR, six high-fidelity (200 Hz) sonomicrometric crystals were implanted. Crystals were positioned at three commissures with their projection at the root base. In post-measurement processing 3D deformation of both AoR was determined and used for computed fluid dynamic modelling in order to evaluate pressure, velocity and shear stress profiles. Results In David AoR: high pressure (> 150 mmHg) and low to moderate shear stress (0-30 Pa) were found from the period of isovolemic contraction to the closure of the aortic valve. At mid diastole pressure augmentation (> 120 mmHg) a low shear stress (0-10 Pa) was registered at the leaflets, three commissures, and intervalvular triangles. In Yacoub AoR: high pressure (110-130 mmHg) with moderate low shear stress (0-30 Pa) was only registered at isovolemic contraction. Conclusions The results show that haemodynamic conditions following a David procedure have a less favourable pattern as compared to a Yacoub AoR. In David AoR, high pressure and low shear stress are present during 2/3 of the cardiac cycle, whereas in Yacoub root, these conditions are present only for a short period of isovolemic contraction.

Objectives: Femoral artery cannulation is routinely used in circulatory support scenarios for cardiorespiratory support in patients with acute cardiac and/or pulmonary decompensation. During prolonged perfusion, this may cause acute ischemia of the leg and, in the worst case, even amputation. The aim of this experimental study was to test a newly designed arterial cannula allowing proximal and distal blood flow. Methods: Veno-arterial cardiopulmonary bypass was established in three calves (67.6 ± 5.1 kg). The venous line was secured by cannulation of the external jugular vein. The arterial line of each animal was secured by cannulation of iliac arteries on both legs. On one side, we used a modified SmartCannula (SmartCannula 18Fr 130 mm) and, on the other side, a standard rectilinear BioMedicus cannula system was used, 19 Fr for retrograde and an 8 Fr BioMedicus shunt for anterograde flow toward the leg. An ultrasonic flow probe was used to quantify the perfusion of the distal leg. Results: At 0.5, 1.0, 1.5, and 2.0 l/min, the anterograde leg blood flow increased steadily for each cannula, but remained higher in the self-expanding cannula. That is, the 8 F rectilinear cannula achieved a blood flow of 0.02 ± 0.01, 0.1 ± 0.04, 0.22 ± 0.09, and 0.21 ± 0.02 l/min, respectively, and the 18 F self-expanding cannula achieved 0.06 ± 0.02, 0.15 ± 0.03, 0.24 ± 0.07 and 0.36 ± 0.04 l/min. Conclusion: The modified self-expanding cannula exhibited superior distal arterial flow compared to the routinely used rectilinear shunt system. This has a potential to reduce ischemic events of the inferior extremity in prolonged perfusion.

The AB-180 is a new implantable centrifugal pump with a low volume dome (10 ml) and a local heparin delivery system which avoids systemic heparinization. This study focuses on its hemodynamic performance. We analyzed 3 anesthetized calves (71.0 +/- 2.5 kg), equipped with arterial pressure (AP), and Swan-Ganz and left atrial pressure (LAP) catheters. The AB-180 pump was installed through a left thoracotomy, with a transmitral left ventricular (LV) inflow cannula inserted via the left appendage and an outflow tract sutured to the descending aorta. LAP, AP, and blood flow across the pump were recorded for various pump speed and in different preload conditions (right atrial pressure = 4, 7, and 10 mm Hg, respectively). The pump significantly unloaded the left heart cavities and was able to increase the mean AP. For an RAP of 10 mm Hg, running the pump at 4,500 rpm decreased the LAP from 11.0 +/- 0.8 mm Hg to 3.0 +/- 0.8 mm Hg (p < 0.001) and augmented the mean AP from 48.2 +/- 6.4 mm Hg to 80.8 +/- 12.1 mm Hg (p < 0.001). A maximal pump flow of 5.6 +/- 0.2 L/min was obtained under these conditions. In addition to the advantage of its particular design, the AB-180 can be considered as an efficient left ventricular assist device (LVAD). It significantly unloads the left heart cavities and ensures efficient systemic AP and blood flow.

The aim of this report is to address the benefits of the minimal invasive venous drainage in a pediatric cardio surgical scenario. Juvenile bovine experiments (67.4+/-11 kg) were performed. The right atrium was cannulated in a trans-jugular way by using the self-expandable (Smart Stat, 12/20F, 430 mm) venous cannula (Smartcannula LLC, Lausanne, Switzerland) vs. a 14F 250 mm (Polystan Lighthouse) standard pediatric venous cannula. Establishing the cardiopulmonary bypass (CPB), the blood flows were assessed for 20 mmHg, 30 mmHg and 40 mmHg of driving pressure. Venous drainage (flow in l/min) at 20 mmHg, 30 mmHg, and 40 mmHg drainage load was 0.26+/-0.1, 0.35+/-0.2 and 0.28+/-0.08 for the 14F standard vs. 1.31+/-0.22, 1.35+/-0.24 and 1.9+/-0.2 for the Smart Stat 12/20F cannula. The 43 cm self-expanding 12/20F Smartcannula outperforms the 14F standard cannula. The results described herein allow us to conclude that usage of the self-expanding Smartcannula also in the pediatric patients improves the flow and the drainage capacity, avoiding the insufficient and excessive drainage. We believe that similar results may be expected in the clinical settings.

Although gravity drainage has been the standard technique for cardiopulmonary bypass (CPB), the development of min imally invasive techniques for cardiac surgery has renewed interest in using vacuum assisted venous drainage (VAVD) Dideco (Mirandola, Italy) has modified the D903 Avant oxygenator to apply a vacuum to its venous reservoir. The impact of VAVD on blood damage with this device is analyzed. Six calves (mean body weight, 71.3 +/- 4.1 kg) were con nected to CPB by jugular venous and carotid arterial cannu lation, with a flow rate of 4-4.51 L/min for 6 h. They were assigned to gravity drainage (standard D903 Avant oxygen ator, n = 3) or VAVD (modified D903 Avant oxygenator, n = 3). The animals were allowed to survive for 7 days. A standard battery of blood samples was taken before bypass, throughout bypass, and 24 h, 48 h, and 7 days after bypass. Analysis of variance was used for repeated measurements. Thrombocyte and white blood cell counts, corrected by hematocrit and normalized by prebypass values, were not significantly different between groups throughout all study periods. The same holds true for hemolytic parameters (lactate dehydrogenase [LDH] and plasma hemoglobin). Both peaked at 24 hr in the standard and VAVD groups: LDH, 2,845 +/- 974 IU/L vs. 2,537 +/- 476 IU/L (p = 0.65), respectively; and plasma hemoglobin, 115 +/- 31 mg/L vs. 89 +/- 455 mg/L (p = 0.45), respectively. In this experimental setup with prolonged perfusion time, VAVD does not increase trauma to blood cells in comparison with standard gravity drainage.