Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Although total body perfusion with extracorporeal life support (ECLS) can be maintained for weeks, individual organ perfusion beyond 12 hours has yet to be achieved clinically. Normothermic ex situ heart perfusion (ESHP) offers the potential for prolonged cardiac preservation. We developed an ESHP system to study the effect of perfusate variables on organ preservation, with the ultimate goal of extending organ perfusion for ≥ 24 hours. Forty porcine hearts were perfused for a target of 12 hours. Hearts that maintained electromechanical activity and had a <3× increase in vascular resistance were considered successful preservations. Perfusion variables, metabolic byproducts, and histopathology were monitored and sampled to identify factors associated with preservation failure. Twenty-two of 40 hearts were successfully preserved at 12 hours. Successful 12-hour experiments demonstrated lower potassium (4.3±0.8 vs. 5.0±1.2 mmol/L, p=0.018) and lactate (3.5±2.8 vs. 4.5±2.9 mmol/L, p=0.139) levels, and histopathology revealed less tissue damage (p=0.003) and less weight gain (p=0.072). Results of these early experiments suggest prolonged ESHP is feasible, and that elevated lactate and potassium levels are associated with organ failure. Further studies are necessary to identify the ideal perfusate for normothermic ESHP.

Objectives: To assess the variation in timing of left atrial decompression and its association with clinical outcomes in pediatric patients supported with venoarterial extracorporeal membrane oxygenation across a multicenter cohort. Design: Multicenter retrospective study. Setting: Eleven pediatric hospitals within the United States. Patients: Patients less than 18 years on venoarterial extracorporeal membrane oxygenation who underwent left atrial decompression from 2004 to 2016. Interventions: None. Measurements and Main Results: A total of 137 patients (median age, 4.7 yr) were included. Cardiomyopathy was the most common diagnosis (47%). Cardiac arrest (39%) and low cardiac output (50%) were the most common extracorporeal membrane oxygenation indications. Median time to left atrial decompression was 6.2 hours (interquartile range, 3.8–17.2 hr) with the optimal cut-point of greater than or equal to 18 hours for late decompression determined by receiver operating characteristic curve. In univariate analysis, late decompression was associated with longer extracorporeal membrane oxygenation duration (median 8.5 vs 5 d; p = 0.02). In multivariable analysis taking into account clinical confounder and center effects, late decompression remained significantly associated with prolonged extracorporeal membrane oxygenation duration (adjusted odds ratio, 4.4; p = 0.002). Late decompression was also associated with longer duration of mechanical ventilation (adjusted odds ratio, 4.8; p = 0.002). Timing of decompression was not associated with in-hospital survival (p = 0.36) or overall survival (p = 0.42) with median follow-up of 3.2 years. Conclusions: In this multicenter study of pediatric patients receiving venoarterial extracorporeal membrane oxygenation, late left atrial decompression (≥ 18 hr) was associated with longer duration of extracorporeal membrane oxygenation support and mechanical ventilation. Although no survival benefit was demonstrated, the known morbidities associated with prolonged extracorporeal membrane oxygenation use may justify a recommendation for early left atrial decompression.

End-stage lung disease (ESLD) causes progressive hypercapnia, dyspnea, and impacts quality of life. Many extracorporeal support (ECS) configurations for CO2 removal resolve symptoms but limit ambulation. An ovine model of pumpless ECS using subclavian vessels was developed to allow for ambulatory support. Vascular grafts were anastomosed to the left subclavian vessels in four healthy sheep. A low-resistance membrane oxygenator was attached in an arteriovenous (AV) configuration. Device function was evaluated in each animal while awake and spontaneously breathing, and while mechanically ventilated with hypercapnia induced. Sweep gas (FiO2=0.21) to the device was increased from 0-15 L/min and arterial and post-device blood gases, as well as post-device air, were sampled. Hemodynamics remained stable with average AV shunt flows of 1.34±0.14 L/min.. In awake animals, CO2 removal was 3.4±1.0 mL/kg/min at maximum sweep gas flow. Respiratory rate decreased from 60±25 at baseline to 30±11 breaths per minute. In animals with induced hypercapnia, PaCO2 increased to 73.9±15.1. At maximum sweep gas flow, CO2 removal was 3.4±0.4 mL/kg/min and PaCO2 decreased to 49.1±6.7 mmHg. Subclavian AV access is effective in lowering PaCO2 and respiratory rate, and is potentially an effective ambulatory destination therapy for ESLD patients.

No abstract

An implantable pediatric artificial lung (PAL) may serve as a bridge to lung transplantation for children with end-stage lung failure (ESLF); however, an animal model of pediatric lung failure is needed to evaluate a PAL’s efficacy before it can enter clinical trials. The objective of this study was to assess ligation of the right pulmonary artery (rPA) as a model for pediatric ESLF. Seven 20-30kg lambs underwent rPA ligation and were recovered and monitored for up to 4 days. Intraoperatively, rPA ligation significantly increased physiologic deadspace fraction (Vd/Vt: baseline=48.6±5.7%, rPA ligation=60.1±5.2%, p=0.012), mean pulmonary arterial pressure (mPPA: baseline=17.4±2.2mmHg, rPA ligation=28.5±5.2mmHg, p<0.001), and arterial partial pressure of carbon dioxide (PaCO2: baseline=40.4±9.3mmHg, rPA ligation=57.3±12.7mmHg, p=0.026). Of the 7 lambs, 3 were unable to be weaned from mechanical ventilation post-operatively, 3 were successfully weaned but suffered cardiorespiratory failure within 4 days, and 1 survived all 4 days. All 4 animals that were successfully weaned from mechanical ventilation had persistent pulmonary hypertension (mPPA=28.6±2.2mmHg) and remained tachypneic (respiratory rate=63±21min−1). Three of the 4 recovered lambs required supplemental oxygen. We conclude that rPA ligation creates the physiologic derangements commonly seen in pediatric end-stage lung failure and may be suitable for testing and implanting a PAL.

Prolonged normothermic ex-vivo heart perfusion (NEVHP) could transform cardiac transplantation. To help identify perfusate components that might enable long-term perfusion, we evaluated the effects of cross-circulated whole blood and cross-circulated plasma from a live paracorporeal animal on donor porcine hearts preserved via NEVHP. Standard perfusion (n=40) utilized red blood cell/plasma perfusate and Langendorf technique for a goal of 12 hours. Cross-circulation groups used a similar circuit with the addition of cross-circulated venous whole blood (XC-Blood; n=6) or cross-circulated filtered plasma (XC-Plasma; n=7) between a live paracorporeal pig under anesthesia and the perfusate reservoir. Data included oxygen metabolism, vascular resistance, lactate production, left ventricular function, myocardial electrical impedance, and histopathologic injury score. All cross-circulation hearts were successfully perfused for 12 hours, compared to 22 of 40 standard perfusion hearts (55%; p=0.002). Both cross-circulation groups demonstrated higher oxygen consumption and vascular resistance than standard hearts from hours 3–12. No significant differences were seen between XC-Blood and XC-Plasma hearts in any variable, including left ventricular dP/dT after 12 hours (1478±700mmHg/s vs. 872±500; p=0.17). We conclude that cross circulation of whole blood or plasma from a live animal improves preservation of function of perfused hearts, and cross-circulated plasma performs similarly to cross-circulated whole blood.

It has been suggested that pulsatile blood flow is superior to continuous flow in cardiopulmonary bypass (CPB). However, adoption of pulsatile flow (PF) technology has been limited due to practically and complexity of creating a consistent physiologic pulse. A pediatric pulsatile rotary ventricular pump (PRVP) was designed to address this problem. We evaluated the PRVP in an animal model, and determined its ability to generate PF during CPB. The PRVP (modified peristaltic pump, with tapering of the outlet of the pump chamber) was tested in 4 piglets (10-12kg). Cannulation was performed with right atrial and aortic cannulae, and pressure sensors were inserted into the femoral arteries. Pressure curves were obtained at different levels of flow and compared with both the animal's baseline physiologic function and a continuous flow (CF) roller pump. Pressure and flow waveforms demonstrated significant pulsatility in the PRVP setup compared to CF at all tested conditions. Measurement of hemodynamic energy data, including the percent pulsatile energy and the surplus hydraulic energy, also revealed a significant increase in pulsatility with the PRVP (p <0.001). PRVP creates physiologically significant PF, similar to the pulsatility of a native heart, and has the potential to be easily implemented in pediatric CPB.