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Hyperammonemia is the pathological accumulation of ammonia in the blood, which can occur in many different clinical settings. Most commonly in adults, hyperammonemia occurs secondary to hepatic dysfunction; however, it is also known to be associated with other pathologies, surgeries, and medications. Although less common, hyperammonemia has been described as a rare, but consistent complication of solid organ transplantation. Lung transplantation is increasingly recognized as a unique risk factor for the development of this condition, which can pose grave health risks—including long-term neurological sequelae and even death. Recent clinical findings have suggested that patients receiving lung transplantations may experience postoperative hyperammonemia at rates as high as 4.1%. A wide array of etiologies has been attributed to this condition. A growing number of case studies and investigations suggest disseminated opportunistic infection with Ureaplasma or Mycoplasma species may drive this metabolic disturbance in lung transplant recipients. Regardless of the etiology, hyperammonemia presents a severe clinical problem with reported mortality rates as high as 75%. Typical treatment regimens are multimodal and focus on 3 main avenues of management: (1) the reduction of impact on the brain through the use of neuroprotective medications and decreasing cerebral edema, (2) augmentation of mechanisms for the elimination of ammonia from the blood via hemodialysis, and (3) the diminishment of processes producing predominantly using antibiotics. The aim of this review is to detail the pathophysiology of hyperammonemia in the setting of orthotopic lung transplantation and discuss methods of identifying and managing patients with this condition.

We previously showed that a vector:lipid delivery system, comprised of a plasmid DNA vector and cationic lipid (lipoplex), when injected into the cerebrospinal fluid (CSF) of rats can deliver reporter genes in vivo efficiently and with widespread expression to the Central Nervous System (CNS). To further characterize this delivery system, we now present experiments that demonstrate the in vivo time-to-peak expression of the reporter gene, firefly luciferase. We infused a formulated lipoplex containing the lipid MLRI [dissymmetric myristoyl (14:0) and lauroyl (12:1) rosenthal inhibitor–substituted compound formed from the tetraalkylammonium glycerol–based DORI] and pNDluc, a luciferase vector, into CSF in the cisterna magna (CM) of the rat. Luciferase activity was followed over time by bioluminescence imaging after injection of luciferin. Our results show that luciferase activity in the CNS of rats is widespread, peaks 72 hours after injection into CM and can be detected in vivo for at least 7–10 days after peak expression. We further show that in contrast to injection into CSF, enzyme activity is not widely distributed after injection of the vector into brain parenchyma, emphasizing the importance of CSF delivery to achieve widespread vector distribution. Finally, we confirm the distribution of firefly luciferase in brain by immunohistochemical staining from an animal that was euthanized at the peak of enzyme expression.

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