Positive inotropic effect of acetylcysteine in cardiomyopathic Syrian hamsters.
Several laboratories have provided indirect evidence that the myocardium of the cardiomyopathic Syrian hamster (CMH) is chronically ischemic on the basis of microvascular spasm. We previously reported evidence supporting a defect in the ryanodine-sensitive sarcoplasmic reticulum calcium release channel (SRCRC) in CMH. A relation between alterations in SRCRC and chronic ischemia has not yet been explored. A potential mechanism could be the effects of changes in redox state on thiol groups. Thiol reagents have previously been shown to regulate calcium release from SRCRC. Accordingly, we studied the inotropic effects of the sulfhydryl donors, acetylcysteine (AC), cysteine, and cystine in CMH. AC was a positive inotrope in isolated papillary muscles prepared from CMH, but not F1B controls (F1B) (p < 0.01). No significant differences were noted in inotropic responses to cysteine or cystine. AC blunted the response of CMH > F1B control papillary muscle preparations to stimulation frequency (p < 0.01). The actual tension generated (in mg/mm2) by CMH was no longer different than F1B with addition of AC (10(-3) M), ryanodine (10(-8) M), or verapamil (5 x 10(-7) M). These findings are consistent with a defect in SRCRC in CMH. This defect may be primary or may provide a novel mechanism for hibernating myocardium owing to chronic ischemia.
Finkel
M S
MS
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania.
Shen
L
L
Oddis
C V
CV
Romeo
R C
RC
Salama
G
G
D000111:Acetylcysteine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D003545:Cysteine / Q000494:pharmacology; D003553:Cystine / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D012433:Ryanodine; D003553:Cystine; D014700:Verapamil; D003545:Cysteine; D000111:Acetylcysteine