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 injury by provoking hypercontracture of cardiomyocytes (acute reperfusion injury). Previous studies indicated that halothane can protect ischemic-reperfused myocardium. The aim of the present study was to analyze on the cellular level the mechanism by which halothane may protect against reoxygenation-induced hypercontracture.


RESULTS
To simulate ischemia-reperfusion, isolated adult rat cardiomyocytes were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in the presence or absence of 0.4 mmol/L halothane. Reoxygenation was started when intracellular Ca2+ (measured with fura 2) had increased to > or = 10(-5) mol/L and pHi (BCECF) had decreased to 6.5. Development of hypercontracture was determined microscopically. In the control group, reoxygenation provoked oscillations of cytosolic Ca2+ (72+/-9 per minute at fourth minute of reoxygenation) accompanied by development of hypercontracture (to 65+/-3% of end-ischemic cell length). When halothane was added on reoxygenation, Ca2+ oscillations were markedly reduced (4+/-2 per minute, P<.001) and hypercontracture was virtually abolished (90+/-4% of end-ischemic cell length, P<.001). Halothane did not influence the recovery of pHi during reoxygenation. Similar effects on Ca2+ oscillations and hypercontracture were observed when ryanodine (3 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ release, or cyclopiazonic acid (10 micromol/L), an inhibitor of the sarcoplasmic reticulum Ca2+ pump, were applied instead of halothane.


CONCLUSIONS
Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture by preventing oscillations of intracellular Ca2+ during the early phase of reoxygenation.
Siegmund
B
B
Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany.
Schlack
W
W
Ladilov
Y V
YV
Balser
C
C
Piper
H M
HM
D018685:Anesthetics, Inhalation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006221:Halothane / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D018685:Anesthetics, Inhalation; D002118:Calcium; D006221:Halothane