The impact of isoflurane during simulated ischemia/reoxygenation on intracellular calcium, contractile function, and arrhythmia in ventricular myocytes.
Some of isoflurane's cellular actions, such as interference with intracellular Ca(2+) handling, inhibition of the respiratory chain, and the capability to produce oxygen radicals, could result in impaired cellular function during ischemia/reoxygenation (I/R). We investigated the effects of isoflurane applied during I/R on intracellular Ca(2+), oxygen radical formation, arrhythmic events, and contractile function in rat cardiomyocytes. Single ventricular myocytes were subjected to 30 min of simulated ischemia followed by 30 min of reoxygenation. After baseline measurements, isoflurane-treated cells were exposed to 1 minimum alveolar concentration of isoflurane in air, whereas control cells were exposed to air only. Cytosolic Ca(2+) overload was observed in the isoflurane group (P < 0.05). During ischemia, systolic cell shortening decreased in both groups. In the isoflurane group, arrhythmic events and hypercontracture occurred more often during I/R, and the recovery of contractility during reoxygenation was less marked (P < 0.05). Furthermore, increased oxygen radical generation was detected in isoflurane-treated myocytes during reoxygenation (P < 0.05). Isoflurane given during I/R in this study induced intracellular Ca(2+) accumulation and impaired cell function. These potentially harmful effects were associated with a diminished Ca(2+) clearance and an accelerated oxygen radical production.
Dworschak
Martin
M
*Department of Anesthesia Research, Mayo Clinic, Rochester, Minnesota, †Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, University Hospital Vienna, Austria, and ‡Department of Anaesthesiology and Intensive Care, University of Münster, Germany.
Breukelmann
Dirk
D
Hannon
James D
JD
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D005609:Free Radicals / Q000378:metabolism; D016257:Fura-2; D006352:Heart Ventricles / Q000187:drug effects; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D005456:Fluorescent Dyes; D005609:Free Radicals; D007530:Isoflurane; D002118:Calcium; D016257:Fura-2