title: The effect of isoflurane during reoxygenation on the sarcoplasmic reticulum and cellular injury in isolated ventricular myocytes.
abstract: In contrast to pretreatment with isoflurane its benefit when applied during reperfusion in rat hearts was only modest. As cellular injury during reoxygenation is greatly determined by sarcoplasmic reticulum (SR) calcium [Ca2+] handling we investigated the effect of isoflurane after simulated ischemia in rat ventricular myocytes. Hypoxic metabolic inhibition was induced by exposure to an acidic medium (pH: 6.3) containing deoxyglucose. Ambient pO2 was reduced to <15 mm Hg. After 30 min, cells were reoxygenated for 30 min with a glucose containing medium (pH: 7.4) in air (Air) or in the presence of isoflurane (Iso), or two SR blockers, i.e. either 3 microM ryanodine (Rya) or 10 microM of cyclopiazonic acid (CPA). During inhibition, diastolic cytosolic calcium ([Ca2+]i) increased and systolic cell shortening decreased. [Ca2+]i further increased in all groups towards the end of reoxygenation. However, [Ca2+]i in the Iso and the Rya group climbed twice as high as in the Air and the CPA group (P < 0.05). Hypercontracture occurred in 23% and 18% in the Iso and the Rya and in 10% and 9% in the Air and the CPA group, respectively (P < 0.05). Cell relengthening and shortening was impaired in Iso, Rya, and CPA treated cells (P < 0.05 vs. Air). Isoflurane given solely during reoxygenation appears to augment cellular injury. Its action seems to be blockade of SR Ca2+ release and Ca2+ efflux. SR Ca2+ overload induces spontaneous Ca2+ oscillations that cause hypercontracture. However, [Ca2+]i does not independently govern cellular systolic and diastolic dysfunction.
authors.affiliation: Department of Anaesthesiology and General Intensive Care, Division of Cardiothoracic and Vascular Anaesthesia and Intensive Care, University Hospital Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. martin.dworschak@meduniwien.ac.at
authors.forename: Martin
authors.initials: M
authors.lastname: Dworschak
authors.forename: Dirk
authors.initials: D
authors.lastname: Breukelmann
authors.forename: James D
authors.initials: JD
authors.lastname: Hannon
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology; D007211:Indoles / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects*
chemical_list: D018685:Anesthetics, Inhalation; D007211:Indoles; D012433:Ryanodine; D007530:Isoflurane; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid