Effects of Isoflurane Dose, Duration of Anoxia, and Reoxygenation on Isoflurane??s Preservation of Energy Balance in Anoxic Isolated Hepatocytes

Abstract

We investigated how the protection of energy status by isoflurane in isolated hepatocytes varied with isoflurane dose, duration of anoxia, and reoxygenation. Hepatocytes were isolated from fed rats and incubated in Krebs buffer under O2/CO2 or N2/CO2 (95/5) for 30 or 90 min, followed by 5 or 30 min of reoxygenation. From measurements of adenosine tri-, di-, and monophosphate (ATP, ADP, AMP) in the cells, energy charge (= [ATP + 1/2 ADP]/[ATP + ADP + AMP]) was calculated to reflect the balance between ATP supply and demand, and total adenine nucleotide (= ATP + ADP + AMP) to indicate the potential maximum ATP level. During 30 min of anoxia, energy charge and total adenine nucleotide steadily increased with isoflurane dose from 0 to 2 minimum alveolar anesthetic concentration, then decreased from 2 to 3 minimum alveolar anesthetic concentration. In short incubations (30-35 min) at 1 minimum alveolar anesthetic concentration isoflurane, there was a modest decrease in energy charge during anoxia, partially prevented by isoflurane and completely reversed by reoxygenation, and no decrease in total adenine nucleotide. In long incubations (90-120 min), there were large decreases in both energy charge and total adenine nucleotide during anoxia, with partial and no reversal by reoxygenation, respectively. Isoflurane partly prevented decreases in both energy charge and total adenine nucleotide during both anoxia and reoxygenation. We conclude that at doses in the clinical range, isoflurane partially protected isolated hepatocytes against decreases in both energy charge and total adenine nucleotide occurring either during short (reversible) or long (irreversible) anoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic Profiles in Urine Reflect Nephrotoxicity of Sirolimus and Cyclosporine following Rat Kidney Transplantation

“…Also, an additive or even synergistic effect on high-energy metabolism does not seem to be a primary reason for the enhancement of the negative effects of cyclosporine on kidney function by sirolimus in our study. This conclusion is further supported by comparison of the energy charges (table 1) that are considered a more robust measure of differences in high-energy metabolism than concentration of single high-energy metabolites [24, 25]. There was no significant difference between the groups treated with cyclosporine and sirolimus alone and in combination, not even between group 6 (CsA10/Rapa1) and the controls.…”

“…In addition to absolute concentrations of single compounds, data are presented as the ‘energy charge’, which is a more robust way of assessing differences. The energy charge is a relative dimensionless value defined as [ATP + 1/2 ADP]/[ATP + ADP + AMP] [25]. …”

Impact of Organ Preservation Using HTK for Graft Flush and Subsequent Storage in UW in Rat Kidney Transplantation

“…However, during hypoxia, ADP and AMP accumulate at the expense of ATP. The energy state of a cell is most accurately described by calculating the energy charge [14] . As expected, in our study, cold ischemic preservation significantly decreased the energy charge in all preservation protocols.…”

“…All compounds quantified were chromatographically separated to avoid ion suppression by other nucleotides. Data are presented as the 'energy charge', a relative dimensionless value defined as [ATP + 1/2 ADP]/[ATP + ADP + AMP] [14] , which is a more robust way of assessing differences.…”

Comparison between sevoflurane and isoflurane anesthesia in pig hepatic ischemia-reperfusion injury

“…Inhalation anesthetics have been shown to exert protective effects against IRI in various organs, including the heart [5,6,9], brain [7], lung [8], and liver [1][2][3][4]. Possible explanations for these protective effects of inhalation anesthetics [21] and the preservation of ATP levels during ischemia, reduced adhesion of polymorphonuclear neutrophils, increased nitric oxide production, inhibition of free radical production, or a reduction in calcium overloading.…”