Protection of isolated cardiomyocytes against reoxygenation-induced hypercontracture by SIN-1C

• Published in: Basic research in cardiology Vol. 93 Suppl 3; pp. 17 - s020
• Main Authors: Siegmund, B, Balser, C, Ladilov, Y V, Piper, H M
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1998
• Subjects: Acetonitriles - pharmacology; Animals; Calcium - metabolism; Male; Morpholines - pharmacology; Myocardial Contraction - drug effects; Myocardial Reperfusion Injury - prevention & control; Rats; Rats, Wistar; Sarcoplasmic Reticulum - metabolism
• ISSN: 0300-8428; 1435-1803
• DOI: 10.1007/s003950050198

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.