Electrical Impedance as a Noninvasive Metric of Quality in Allografts Undergoing Normothermic Ex Vivo Lung Perfusion

Abstract

Ex vivo lung perfusion (EVLP) increases the pool of suitable organs for transplant by facilitating assessment and repair at normothermia, thereby improving identification of quality of marginal organs. However, there exists no current objective approach for assessing total organ edema. We sought to evaluate the use of electrical impedance as a metric to assess total organ edema in lungs undergoing EVLP. Adult porcine lungs (40 kg) underwent normothermic EVLP for 4 hours. To induce varying degrees of lung injury, the allografts were perfused with either Steen, a modified cell culture media, or 0.9% normal saline. Physiologic parameters (peak airway pressure and compliance), pulmonary artery and left atrial blood gases, and extravascular lung water measurements were evaluated over time. Wet-to-dry ratios were evaluated postperfusion. Modified Murray scoring was used to calculate lung injury. Impedance values were associated with lung injury scores ( p = 0.007). Peak airway pressure ( p = 0.01) and PaO 2 /FiO 2 ratios ( p = 0.005) were both significantly associated with reduced impedance. Compliance was not associated with impedance ( p = 0.07). Wet/dry ratios were significantly associated with impedance and Murray Scoring within perfusion groups of Steen, Saline, and Modified Cell Culture ( p = 0.0186, 0.0142, 0.0002, respectively). Electrical impedance offers a noninvasive modality for measuring lung quality as assessed by tissue edema in a porcine model of normothermic EVLP. Further studies evaluating the use of impedance to assess organ edema as a quality marker in human clinical models and abdominal organs undergoing ex vivo perfusion warrant investigation.

Figure 1.

Normothermic EVLP circuit. A: Illustration of the flow of the EVLP circuit. Outflow from the left atria drained into a reservoir and then the centrifugal pump provided consistent cardiac output. Perfusate then flowed through the membrane oxygenator into the heater/cooler, through the leukocyte filter and back into the pulmonary artery. B: Image of porcine lung on the EVLP circuit. C: Illustration depicts the location of the PiCCO catheter in the left atrial cannula. Cold saline was flushed through the pulmonary artery and detected by the a sensor in the outflow of the left atria. D: Image of the PiCCO catheter inserted into the EVLP circuit and the blue sensor that provided the readouts. EVLP, ex vivo lung perfusion.

Figure 2.

Porcine lungs during EVLP. Representative images of the porcine lungs after EVLP with (A) normal saline, (B) modified cell culture media, and (C) Steen perfusates. EVLP, ex vivo lung perfusion.

Figure 3.

Injury and edema assessments and correlations to impedance. A: Linear regression comparing impedance values in Ohms to Murray scoring. B: Linear regression comparing peak airway pressure measured in cm H₂O to impedance measured in Ohms. C: Linear regression comparing compliance measured in dynamic 20 compliance (Cdyn) to impedance measured in Ohms. D: Linear regression comparing impedance with PaO₂/FiO₂ ratios.

Figure 4.

PiCCO assessment of extra vascular lung water. Polynomial regression comparing impedance with extra vascular lung water. Note as the impedance decreases the extra vascular lung water increases.

Figure 5.

Illustration of the overall concept electrical impedance to assess edema. A: Diagram of normal alveoli after perfusion with Steen solution. Note the minimal edema and thus high resistance to electrical current. B: Diagram of alveoli with increased interstitial fluid after perfusion with modified cell culture media. As the amount of fluid increases, the conduction of electrical current across the cells also increases. This is directly related to the decrease in resistance or impedance across these cells. C: Diagram of alveoli with severe damage after perfusion with normal saline solution. This scenario allows for the maximum electrical flow and thus the smallest impedance values.