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Isoflurane applied during ischemia enhances intracellular calcium accumulation in ventricular myocytes in part by reactive oxygen species

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Abstract:

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 ([Ca2+]i) overload during ischemia. We therefore investigated isoflurane's effects on intracellular Ca2+ 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 Ca2+ homeostasis during ischemia in both groups, the intracellular ROS scavenger, N‐mercaptopropionylglycine (MPG), was added to the superfusion buffer. The fluorescent ratiometric Ca2+ dye fura-2 was employed to determine [Ca2+]i. Results: 

Resting and peak [Ca2+]i increased in the ischemia and the ischemia + iso group. However, Ca2+ 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 Ca2+ transient decline but did not further diminish the amplitude of the transient during ischemia. Conclusion: 

Isoflurane when applied during ischemia appears to worsen [Ca2+]i overload, which is caused by impeding Ca2+ clearance. As MPG mitigated the increase in [Ca2+]i, isoflurane seems to enhance ROS-mediated effects on intracellular Ca2+ handling in cellular ischemia.

Keywords: Intracellular calcium handling; ischemic calcium overload; isoflurane; myocardial ischemia; radical oxygen species; ventricular myocytes

Document Type: Research Article

DOI: https://doi.org/10.1111/j.0001-5172.2004.00410.x

Affiliations: Department of Anesthesia Research, Mayo Clinic, Rochester, MN

Publication date: 2004-07-01

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