Drs. Piantadosi, Welty-Wolf, Carraway). Animal models have been developed to study acute lung injury due to oxygen toxicity and sepsis. Methods of assessment include gas exchange (blood gases and multiple inert gas elimination), mechanics, lung morphometry, and measurement of pulmonary inflammatory responses and activation of the coagulation system. In addition, mechanisms or systemic organ injury, particularly those involving mitochondria, are being investigated.
Clinically, mitochondrial damage correlates with MODS and higher mortality. In sepsis mitochondria are damaged early and selectively, especially mtDNA. Damage mediated by ROS/RNS generated by the immune response promotes apoptosis. MtDNA transcription in vital organs is suppressed while nuclear genes are activated for mitochondrial proteins such as Tfam, Pol-γ.
Postlipopolysaccharide Oxidative Damage of Mitochondrial DNAHagir B. Suliman, Martha S. Carraway and Claude A. Piantadosi. American Journal of Respiratory and Critical Care Medicine Vol 167. pp. 570-579,