A Model of Pediatric End-Stage Lung Failure in Small Lambs <20 kg.

One in five children with end-stage lung failure (ESLF) die while awaiting lung transplant. No suitable animal model of ESLF exists for the development of artificial lung devices for bridging to transplant. Small lambs weighing 15.7 ± 3.1 kg (n = 5) underwent ligation of the left anterior pulmonary artery (PA) branch, and gradual occlusion of the right main PA over 48 hours. All animals remained hemodynamically stable. Over seven days of disease model conditions, they developed pulmonary hypertension (mean PA pressure 20 ± 5 vs. 33 ± 4 mm Hg), decreased perfusion (SvO2 66 ± 3 vs. 55 ± 8%) with supplemental oxygen requirement, and severe tachypneic response (45 ± 9 vs. 82 ± 23 breaths/min) (all p < 0.05). Severe right heart dysfunction developed (tricuspid annular plane systolic excursion 13 ± 3 vs. 7 ± 2 mm, fractional area change 36 ± 6 vs. 22 ± 10 mm, ejection fraction 51 ± 9 vs. 27 ± 17%, all p < 0.05) with severe tricuspid regurgitation and balloon-shaped dilation of the right ventricle. This model of pediatric ESLF reliably produces pulmonary hypertension, right heart strain, and impaired gas exchange, and will be used to develop a pediatric artificial lung.

Nitric Oxide Attenuates the Inflammatory Effects of Air During Extracorporeal Circulation.

Cardiopulmonary bypass causes a systemic inflammatory response reaction that may contribute to postoperative complications. One cause relates to the air/blood interface from the extracorporeal circuit. The modulatory effects of blending nitric oxide (NO) gas into the ventilation/sweep gas of the membrane lung was studied in a porcine model of air-induced inflammation in which NO gas was added and compared with controls with or without an air/blood interface. Healthy swine were supported on partial bypass under four different test conditions. Group 1: no air exposure, group 2: air alone, group 3: air plus 50 ppm NO, and group 4: air plus 500 ppm NO. The NO gas was blended into the ventilation/sweep site of the membrane lung. The platelets and leucocytes were activated by air alone. Addition of NO to the sweep gas attenuated the inflammatory response created by the air/blood interface in this model.

Ex Vivo Heart Perfusion for 72 Hours Using Plasma Cross Circulation.

Preservation of a donor heart for transplantation is limited to 6-8 hours. Based on our demonstration of 12 hour perfusion with plasma cross circulation, this study aimed to evaluate ex vivo heart perfusion (EVHP) for up to 72 hours using cross plasma circulation (XC-plasma) from a live, awake paracorporeal sheep (PCS). Six ovine hearts were perfused for 72 hours using plasma cross circulation at a rate of 1 L/min with a live, awake PCS. Controls were seven perfused hearts without cross circulation. Experiments were electively ended at 72 hours, and epinephrine (0.1 mg) was delivered to demonstrate hormonal responsiveness. All controls failed at 6-10 hours. All six hearts perfused for 72 hours maintained normal heart function, metabolism, and responsiveness to epinephrine. Blood gases, electrolytes, and lactate levels were normal and stable throughout the study. All hearts appeared suitable for transplantation. We have demonstrated successful normothermic EVHP for 72 hours.

Low-Resistance, Concentric-Gated Pediatric Artificial Lung for End-Stage Lung Failure.

Children with end-stage lung failure awaiting lung transplant would benefit from improvements in artificial lung technology allowing for wearable pulmonary support as a bridge-to-transplant therapy. In this work, we designed, fabricated, and tested the Pediatric MLung-a dual-inlet hollow fiber artificial lung based on concentric gating, which has a rated flow of 1 L/min, and a pressure drop of 25 mm Hg at rated flow. This device and future iterations of the current design are designed to relieve pulmonary arterial hypertension, provide pulmonary support, reduce ventilator-associated injury, and allow for more effective therapy of patients with end-stage lung disease, including bridge-to-transplant treatment.

Splenic development and injury in premature lambs supported by the artificial placenta.

INTRODUCTION: The purpose of this study is to evaluate splenic effects during artificial placenta (AP) support. METHODS: AP lambs (118-121 d, n = 14) were delivered and placed on the AP support for a goal of 10-14 days. Cannulation used right jugular drainage and umbilical vein reinfusion. Early (ETC; 115-120 d; n = 7) and late (LTC; 125-131 d; n = 7) tissue controls were delivered and immediately sacrificed. Spleens were formalin fixed, H&E stained, and graded for injury, response to inflammation, and extramedullary hematopoiesis (EMH). CD68 and CD163 stains were used to assess for macrophage activation and density. Clinical variables were correlated with splenic scores. Groups were compared using Fisher's Exact Test and descriptive statistics. p < 0.05 indicated significance. RESULTS: Mean survival for AP lambs was 12 ±â€¯5 d. There was no necrosis found in any of the groups. Vascular congestion and sinusoidal histiocytosis did not significantly differ between AP and control groups (p = 0.72; p = 0.311). There were significantly more pigmented macrophages (p = 0.008), CD163 (p = <0.001), and CD68 (p = <0.001) stained cells in the AP group. ETC and LTC demonstrated more EMH than AP spleens (p = <0.001). CONCLUSIONS: During AP support, spleens appear to develop normally and exhibit an appropriate inflammatory response. After initiation of AP support, EMH transitions away from the spleen. STUDY TYPE: Research Paper/Therapeutic Potential. LEVEL OF EVIDENCE: N/A.