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: B Siegmund, C Balser, Y V Ladilov, H M Piper
• Journal: Basic research in cardiology (Basic Res Cardiol) Vol. 93 Suppl 3 Pg. 17-20 ( 1998) ISSN: 0300-8428 [Print] Germany
• PMID: 9879438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetonitriles
• Morpholines
• SIN 1C
• Calcium

Topics

• Acetonitriles (pharmacology)
• Animals
• Calcium (metabolism)
• Male
• Morpholines (pharmacology)
• Myocardial Contraction (drug effects)
• Myocardial Reperfusion Injury (prevention & control)
• Rats
• Rats, Wistar
• Sarcoplasmic Reticulum (metabolism)