(Circulation. 1997;96:4372-4379.)
© 1997 American Heart Association, Inc.
Articles |
Halothane Protects Cardiomyocytes Against Reoxygenation-Induced Hypercontracture
From the Physiologisches Institut, Justus-Liebig-Universität, Giessen, and Institut für Klinische Anaesthesiologie, Heinrich-Heine-Universität, Düsseldorf (W.S.), Germany.
Correspondence to H. Michael Piper, Physiologisches Institut, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany. E-mail michael.piper{at}physiologie.med.uni-giessen.de
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.
Methods and 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 
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 µmol/L), an inhibitor of the
sarcoplasmic reticulum Ca2+ release, or
cyclopiazonic acid (10 µmol/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.
Key Words: reperfusion • prevention • ischemia • calcium • halothane
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