The effect of isoflurane during reoxygenation on the sarcoplasmic reticulum and cellular injury in isolated ventricular myocytes.
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.
Dworschak
Martin
M
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
Breukelmann
Dirk
D
Hannon
James D
JD
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*
D018685:Anesthetics, Inhalation; D007211:Indoles; D012433:Ryanodine; D007530:Isoflurane; D000252:Calcium-Transporting ATPases; D002118:Calcium; C000543:cyclopiazonic acid