Ascorbic acid prolongs the viability and stability of isolated perfused lungs: A mechanistic study using 31P and hyperpolarized 13C nuclear magnetic resonance

In vivo pH mapping of injured lungs using hyperpolarized [1‐13C]pyruvate

“…Therefore, the reported pH values represent a weighted average of intracellular and extracellular pH with unknown weighting coefficients. The uptake of pyruvate leads to the production of some additional intracellular bicarbonate and CO 2 via pyruvate dehydrogenase, which will also contribute to the measured pH, although this contribution should be negligible relative to the total bicarbonate and CO 2 signal (26). Previous studies have demonstrated strong agreement between the pH measured using exogenous HP bicarbonate and the extracellular pH measured using a 31 P pH probe, indicating that the pH being measured is predominantly extracellular (13).…”

The use of hyperpolarized carbon-13 magnetic resonance for molecular imaging

“…Most studies to date have evaluated the data using one of two divergent methods: through quantification of signal ratios or by deriving fitting parameters from a kinetic model. Relative quantification typically reports the metabolite signal (area under the curve) normalized by either the delivered HP probe’s signal, or the total carbon metabolite signal [161–164]. The advantage of this method is that it is trivial to perform, but it limits a direct comparison between studies because the normalization does not explicitly account for the delivered probe concentration, transport mechanics, T 1 or RF-induced relaxation or other sources of signal variation.…”

“…A greater than four-fold increase in HP pyruvate-to-lactate ratio was also found during the inflammatory phase of a bleomycin induced lung injury model in perfused rat lungs, which was well correlated with the neutrophil count via histology (figure F) [124]. Another HP [1- 13 C]pyruvate study investigated the mechanism by which ascorbate prolongs the viability of isolated perfused lungs [164]. It was found that ascorbate enhanced viability via interaction with the electron transport chain, as opposed to its more common role as a general antioxidant.…”

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“…1 While ascorbic acid is the main water-soluble antioxidant in human plasma, the study refers its beneficial effects to the ability to interact with electron transport chain rather than to its antioxidant actions. 1 The ischemic reperfusion injury (IRI) during lung transplant results in inhibition of sodium (Na+) potassium-(K+) ATPase and various K+ channels, leading to Na+ influx and persistant cell memberane depolarization. Under physiological conditions, active K+ channels are responsible to antagonize Na+ influx and to establish memberane hyperpolarization.…”

“…3 Reactive oxygen species also inhibit pyruvate dehydrogenase complex in a dose-dependent manner 1 and prime graft inflammasomes. Primed inflammasomes are then triggered in action by the simultaneous drop of K+ levels, leading to increased production of inflammatory cytokines.…”