Premium
Isoflurane applied during ischemia enhances intracellular calcium accumulation in ventricular myocytes in part by reactive oxygen species
Author(s) -
Dworschak M.,
Breukelmann D.,
Han J. D.
Publication year - 2004
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.0001-5172.2004.00410.x
Subject(s) - isoflurane , ischemia , medicine , reactive oxygen species , calcium , intracellular , myocyte , calcium in biology , anesthesia , pharmacology , chemistry , biochemistry
Background: Isoflurane applied before myocardial ischemia has a beneficial preconditioning effect which involves generation of reactive oxygen species (ROS); ROS, however, have been implicated in critical cytosolic calcium ([Ca 2+ ] i ) overload during ischemia. We therefore investigated isoflurane's effects on intracellular Ca 2+ handling in ischemic ventricular myocytes and the association with ROS. Methods: Simulated ischemia was induced in electrically stimulated rat ventricular myocytes for 30 min (ischemia). Isoflurane‐treated cells were additionally exposed to 1MAC of isoflurane (ischemia + iso). To determine the contribution of ROS to Ca 2+ homeostasis during ischemia in both groups, the intracellular ROS scavenger, N‐mercaptopropionylglycine (MPG), was added to the superfusion buffer. The fluorescent ratiometric Ca 2+ dye fura‐2 was employed to determine [Ca 2+ ] i . Results: Resting and peak [Ca 2+ ] i increased in the ischemia and the ischemia + iso group. However, Ca 2+ accumulation was most prominent in isoflurane‐treated cardiomyocytes ( P < 0.05) and could be mitigated by MPG in both groups ( P < 0.001). Isoflurane also decreased the rate constant of the Ca 2+ transient decline but did not further diminish the amplitude of the transient during ischemia. Conclusion: Isoflurane when applied during ischemia appears to worsen [Ca 2+ ] i overload, which is caused by impeding Ca 2+ clearance. As MPG mitigated the increase in [Ca 2+ ] i , isoflurane seems to enhance ROS‐mediated effects on intracellular Ca 2+ handling in cellular ischemia.