title: Protection of isolated cardiomyocytes against reoxygenation-induced hypercontracture by SIN-1C.
abstract: Previous studies have shown that SIN-1C (N-morpholinoiminoacetonitrile) can protect ischemic-reperfused myocardium. The aim of the present study was to analyse on the cellular level the mechanism by which SIN-1C may exert this effect. To simulate ischemia-reperfusion, isolated adult rat cardiomyocytes were incubated at pH 6.4 under anoxia and reoxygenated at pH 7.4 in presence or absence of SIN-1C. Reoxygenation was started when intracellular Ca2+ (measured with fura-2) had increased to > or = 10(-5) mol/L and pHi (BCECF) decreased to 6.6. Development of hypercontracture was determined microscopically. In the control group reoxygenation provoked oscillations of cytosolic Ca2+ (60.9 +/- 9.6 min-1 at 5 min of reoxygenation) accompanied by development of hypercontracture (to 77.2 +/- 3.8% of end-ischemic cell length). When SIN-1C was added upon reoxygenation, Ca2+ oscillations were markedly reduced (27.0 +/- 4.5 min-1, p < 0.001) and hypercontracture virtually abolished (90.6 +/- 2.0% of end-ischemic cell length, p < 0.001). SIN-1C did not influence the recovery of pHi during reoxygenation. The results indicate that SIN-1C protects cardiomyocytes against reoxygenation-induced hypercontracture by its ability to suppress oscillations of intracellular Ca2+ during the early phase of reoxygenation.
authors.affiliation: Physiologisches Institut Justus-Liebig-Universität, Giessen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Siegmund
authors.forename: C
authors.initials: C
authors.lastname: Balser
authors.forename: Y V
authors.initials: YV
authors.lastname: Ladilov
authors.forename: H M
authors.initials: HM
authors.lastname: Piper
mesh_terms: D000097:Acetonitriles / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D000097:Acetonitriles; D009025:Morpholines; C093946:SIN 1C; D002118:Calcium