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

Abstract

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.

Levosimendan does not improve survival time in a rat model of verapamil toxicity

“…There is, however, data that shows it has adverse effects on myocardium. Isoflurane in certain settings can induce a rise in intracellular calcium, especially during hypoxia [11], although this rise in intracellular calcium has not been shown to have lusitopic effects [12]. In combination with levosimendan, this effect may account for the fact the experimental animals expired relatively shortly after the administration of the second dose of levosimendan.…”

The effect of isoflurane during reoxygenation on the sarcoplasmic reticulum and cellular injury in isolated ventricular myocytes

“…(Quaife et al, 1991) Augmented release of oxygen radicals has been observed in the setting we employed in the presence of isoflurane during reoxygenation after simulated ischemia. (Dworschak et al, 2004a) Indirect evidence also suggests that isoflurane during metabolic inhibition enhances myoplasmic Ca 2+ accumulation via liberation of a different kind of oxygen radical species. (Dworschak et al, 2004b) The multifactorial cause of cellular dysfunction and necrosis is supported by the finding that elevated [Ca 2+ ] i results in excessive Ca 2+ dependent myofilament crossbridge cycling, which again could be prevented by butanedione monoxime that inhibits force development.…”

“…However, an enhanced liberation of oxygen radical species may also contribute to these observations. (Dworschak et al, 2004a) …”

Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice

“…The detailed I/R protocol has already been described elsewhere (8). In brief, hypoxic conditions (PO 2 Ͻ 15 mmHg) were achieved by vigorously bubbling the solution with nitrogen and introducing nitrogen under the hood of the perfusion chamber as has been demonstrated by Henderson and Brutsaert (17).…”