HALOTHANE PROTECTS CARDIOMYOCYTES AGAINST REOXYGENATION-INDUCED HYPERCONTRACTURE

Background Resupply of oxygen to the myocardium after extended periods of ischemia or hypoxia can rapidly aggravate the already existing inj ury by provoking hypercontracture of cardiomyocytes (acute reperfusion injury). Previous studies indicated that halothane can protect ischem ic-reperfused myocardium. The aim of the present study was to analyze on the cellular level the mechanism by which halothane may protect aga inst reoxygenation-induced hypercontracture. Methods and Results To si mulate ischemia-reperfusion, isolated adult rat cardiomyocytes were in cubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in the prese nce or absence of 0.4 mmol/L halothane. Reoxygenation was started when intracellular Ca2+ (measured with fura 2) had increased to greater th an or equal to 10(-5) mol/L and pH(i) (BCECF) had decreased to 6.5. De velopment of hypercontracture was determined microscopically. In the c ontrol group, reoxygenation provoked oscillations of cytosolic Ca2+ (7 2+/-9 per minute at fourth minute of reoxygenation) accompanied by dev elopment of hypercontracture (to 65+/-3% of end-ischemic cell length). When halothane was added on reoxygenation, Ca2+ oscillations were mar kedly reduced (4+/-2 per minute, P<.001) and hypercontracture was virt ually abolished (90+/-4% of end-ischemic cell length, P<.001). Halotha ne did not influence the recovery of pH(i) during reoxygenation. Simil ar effects on Ca2+ oscillations and hypercontracture wire observed whe n ryanodine (3 mu mol/L), an inhibitor of the sarcoplasmic reticulum C a2+ release, or cyclopiazonic acid (10 mu mol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, were applied instead of halothane. C onclusions Halothane protects cardiomyocytes against reoxygenation-ind uced hypercontracture by preventing oscillations of intracellular Ca2 during the early phase of reoxygenation.