The Impact of Isoflurane During Simulated Ischemia/Reoxygenation on Intracellular Calcium, Contractile Function, and Arrhythmia in Ventricular Myocytes

In Brief Some of isoflurane’s cellular actions, such as interference with intracellular Ca2+ 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 Ca2+, 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 Ca2+ 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 Ca2+ accumulation and impaired cell function. These potentially harmful effects were associated with a diminished Ca2+ clearance and an accelerated oxygen radical production. IMPLICATIONS: Isoflurane, a volatile anesthetic, administered during ischemia/reoxygenation, aggravated functional impairment in heart muscle cells. These alterations were probably caused by interference with intracellular Ca2+ handling proteins and by generation of oxygen radicals. Cardioprotection by isoflurane when given before ischemia should be reevaluated in situations of continuing ischemia and subsequent reperfusion.