flexiVent Assessment of the Efficacy of Mitochondrial Transplantation for Lung Ischemia Reperfusion Injury
Congratulations to Dr. James McCully’s team at Harvard Medical School for their recent publication “Mitochondrial Transplantation Enhances Murine Lung Viability and Recovery after Ischemia Reperfusion Injury”, published in Lung Cellular and Molecular Physiology!
First authors, Dr. Kamila Moskowitzova and Dr. Arzoo Orfany, present a powerful demonstration of the efficacy of syngeneic mitochondrial transplantation, via vascular or nebulization delivery, for the amelioration of ischemia reperfusion-induced acute lung injury. Reported endpoints include histological assessments of lung injury, BAL cell and cytokine analysis, and the assessment of lung mechanics with the flexiVent.
The authors use the flexiVent to control delivery of nebulized mitochondria and to make a comprehensive evaluation of respiratory mechanics using complimentary techniques including: Pressure-Volume loops, Snapshot and Quickprime perturbations, and assessments of peak-inspiratory pressures and inspiratory capacities.
Taking advantage of the nebulization template in the flexiVent software, 3×108 mitochondria is delivered to intubated subjects using the Aeroneb nebulizer. Nebulization occurs over 10 second intervals, spaced 1 minute apart for a total of 40 seconds, synchronizing with inspiration to improve delivery efficiency. Using PET-μCT imaging, it is easy to see the lung specific deposition of the mitochondria without re-distribution to other organs, see Figure 1.
Figure 1: PET-μCT imaging of 18F-Rhodamine 6G labeled mitochondria delivered to the lungs of Wistar male rats via nebulization with the flexiVent.
24 hrs following induction of ischemia reperfusion injury and mitochondria/control delivery, significant improvements in lung mechanics correlate with the mitochondrial transplantation. Figure 2 presents PV loops from all groups, with improved static compliance and increased hysteresis in the mitochondria transplanted groups (both nebulized and vascular delivery), over the vehicle controls. Figure 3 demonstrates the amelioration lung injury, as assessed with the Constant Phase model (QuickPrime maneuver) in the form of increased Newtonian Resistance and Tissue Damping.
Figure 2: Pressure-volume loops in mice 24 hrs following ischemia reperfusion injury or sham treatment, with vehicle or mitochondrial transplantation via vascular delivery (Vehicle V & Mito V) or nebulized delivery (Mito Neb or Vehicle Neb).
Figure 3: Newtonian Resistance and Tissue damping (G) in mice 24 hrs following ischemia reperfusion injury or sham treatment, with vehicle or mitochondrial transplantation via vascular delivery (Vehicle V & Mito V) or nebulized delivery (Mito Neb or Vehicle Neb).
This study provides compelling evidence for the efficacy of mitochondrial transplantation for lung ischemia reperfusion injury and a great example of how the flexiVent is used to provide comprehensive assessments of lung injury.