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Background: For children with severe lung disease that cannot wean from ECMO, an implantable artificial lung would permit extubation and support gradual lung recovery from acute disease or provide a bridge to transplantation. We evaluate the function of the novel Pediatric MLung—an efficient, implantable, pumpless artificial lung developed specifically for children—in healthy animal subjects. Methods: Adolescent “mini sheep” weighing 12-20 …

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.

Background: Extracorporeal CPR (ECPR) is used to provide circulatory stability for organ perfusion and oxygen delivery (DO 2 ) after refractory cardiac arrest (CA). Hemodynamic measurements during ECPR may not necessarily indicate adequate perfusion at the microcirculatory level where DO 2 , oxygen consumption (VO 2 ), and oxygen exchange (O 2 ER) are most critical. In this study, we used sidestream dark-field imaging to measure total vessel density (TVD) to evaluate sublingual microcirculatory flow in a swine model of refractory CA and ECPR. Hypothesis: We hypothesize that TVD can provide real-time assessment of tissue perfusion during post-cardiac arrest ECPR that correlates with traditional measures of tissue oxygenation. Methods: Swine (8) were anesthetized and instrumented for hemodynamic monitoring. Ventricular fibrillation (VF) was induced and CPR initiated after 8min. CPR was administered using a combination of manual and mechanical chest compressions. During CPR the femoral vessels were instrumented for delivery of veno-arterial ECPR. ECPR was initiated 45min after arrest to simulate refractory CA. Sublingual TVD was measured at baseline and after 15min, 1, 2, and 3 hours of ECPR. Results: A one-way ANOVA showed significant difference between baseline TVD: 12.2(2.3)mm -1 and at 3 hours into ECPR: 6.4(3.0)mm -1 (p=0.005). TVD was highly correlated with circuit flow but not with Mean Arterial Pressure (MAP) (r=0.903, p=0.036; r=0.063, p=0.920). In addition, TVD was highly correlated with DO 2 , and lactate, (r= 0.897, p=0.039; r=-0.883, p=0.047) and moderately with VO 2 , O 2 ER, and ScvO 2 (r= 0.776, -0.370, 0.558) respectively. Conclusion: TVD appears to provide a reliable real-time assessment of tissue perfusion during post-cardiac arrest ECPR. The relationships between TVD and MAP, and TVD and flow also suggest that optimization of flow may be more important than optimizing pressure to achieve adequate tissue perfusion during ECPR.

Introduction: Prolonged cardiac arrest (CA) eligible for ECPR has pathologic features that are more pronounced than CA durations in which ROSC is typically achieved. One such feature is consumptive coagulopathy resulting in microvascular thrombosis and no-reflow. In this study we examined the impact of no-flow time on CA coagulopathy during prolong CPR in swine Hypothesis: No-flow time amplifies the coagulopathy of prolonged cardiac arrest. Methods: Animals were anesthetized and instrumented for hemodynamic monitoring. After 4 or 8 min of untreated ventricular fibrillation (groups CA-4 and CA-8, n=5/group), goal-directed CPR was initiated and continued for a total arrest time of 45 minutes. Viscoelastic properties of clot formation and fibrinolysis were measured by TEG in whole blood at baseline and at the end of resuscitation protocol. Rate of fibrin activation (Angle alpha), Maximum amplitude (MA), Time to MA (TMA), and reduction of clot after 30 min (CL30) were measured to describe coagulation status. Results: TEG showed reduction in clot strength after the CPR protocol. For groups CA-4 and CA-8, Alpha declined from 71(4) to 55(7) and from 68(5) to 51(9) deg, MA reduced from 75(2) to 58(7) and from 73(3) to 53(11) mm and TMA prolonged from 21(2) to 27(4) and from 20(4) to 25(2) min. CL30 increased from 95(2) to 97(2) and from 96(2) to 100(1) % (all p Conclusion: In this clinically relevant model of prolonged CA with consumptive coagulopathy, the reduction of clot formation and clot strength after 45 minutes of CA and CPR was not significantly different with 4 and 8 min no-flow time. However, clot lysis was more reduced after 8-min no-flow. Further studies are needed to determine the impact of no-flow time on CA coagulopathy at the microvascular level.

Introduction: The interval from cardiac arrest (CA) to initiation of chest compressions (no-flow time) plays an important role in outcome of CA. The purpose of this study was to evaluate impact of no-flow time on the effectiveness of a goal-direct CPR strategy during prolonged cardiac arrest. Hypothesis: The effectiveness of goal-directed CPR declines with increased no-flow time. Methods: Porcine model of CA was utilized with a period of untreated ventricular fibrillation of 4 or 8 min (groups CA-4, CA-8, n=5/group) followed by a goal-directed CPR protocol for up to 40 minutes. Manual and mechanical chest compressions with impedance threshold device were used sequentially to achieve PetCO2 goal >20 mmHg. Epinephrine infusion and boluses were adjusted with the goal of achieving an arterial diastolic blood pressure >35 mmHg. Hemodynamic parameters were collected throughout the protocol, averaged in 5-minute intervals and compared between groups by an unpaired t-test. Results: A higher average DBP was achieved in the CA-4 vs. CA-8 group during CPR (19 ± 11 mmHg vs. 12 ± 9 mmHg: p Conclusion: In this swine model of prolonged VF cardiac arrest, increased no-flow time limits the effectiveness of a goal-directed CPR strategy. Moreover, the response to standard dose of epinephrine was higher after shorter no-flow time.