Inhalational anesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies.
BACKGROUND
The authors hypothesized that inhalational anesthetics induced cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of inositol 1,4,5-trisphosphate (IP3) receptors, with isoflurane having greater potency than sevoflurane or desflurane.


METHODS
The authors treated DT40 chicken B lymphocytes with total IP3 receptor knockout or their corresponding wild-type control cells with equipotent exposure to isoflurane, sevoflurane, and desflurane. The authors then determined the degree of cell damage by counting the percentage of annexin V- or propidium iodide-positively stained cells or measuring caspase-3 activity. They also studied the changes of calcium concentrations in the endoplasmic reticulum, cytosol, and mitochondria evoked by equipotent concentrations of isoflurane, sevoflurane, and desflurane in both types of DT40 cells.


RESULTS
Prolonged use of 2 minimal alveolar concentration sevoflurane or desflurane (24 h) induced significant cell damage only in DT40 wild-type and not in IP3 receptor total knockout cells, but with significantly less potency than isoflurane. In accord, all three inhalational anesthetics induced significant decrease of calcium concentrations in the endoplasmic reticulum, accompanied by a subsequent significant increase in the cytosol and mitochondrial calcium concentrations only in DT40 wild-type and not in IP3 receptor total knockout cells. Isoflurane treatment showed significantly greater potency of effect than sevoflurane or desflurane.


CONCLUSIONS
Inhalational anesthetics may induce cell damage by causing abnormal calcium release from the endoplasmic reticulum via excessive activation of IP3 receptors. Isoflurane has greater potency than sevoflurane or desflurane to cause calcium release from the endoplasmic reticulum and to induce cell damage.
Yang
Hui
H
Department of Anesthesiology and Critical Care, University of Pennsylvania, PA, USA.
Liang
Ge
G
Hawkins
Brian J
BJ
Madesh
Muniswamy
M
Pierwola
Andrew
A
Wei
Huafeng
H
D018685:Anesthetics, Inhalation / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000648:ultrastructure*; D006706:Homeostasis / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008738:Methyl Ethers / Q000633:toxicity*; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D015220:Calcium Channels; D008738:Methyl Ethers; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane; D053148:Caspase 3; D002118:Calcium