[Protective effects of SH-compounds on ischemia reperfusion induced arrhythmias in the isolated rat heart].
Protective effects of cysteine (Cys), N-acetylcysteine (NAC), cysteamine (MEA), cystamine (CSSC) and aminopropylmethylisothiourea (APMT) on ischemia/reperfusion induced arrhythmias were studied in isolated Langendorff perfused rat hearts. The arrhythmias were caused by ligation of the anterior descending branch of the left coronary artery for 10 min and reperfused for 5 min. The drugs were dissolved in saline (NS) and perfused through a peristaltic pump system at 0.1, 0.6 or 3.6 mumol/min (n = 10), starting from 10 min before ligation up to 5 min after reperfusion. The control hearts were perfused with NS. The results showed that Cys, NAC and MEA pursued at 0.6-3.6 mumol/min significantly reduced the incidence of ventricular fibrillation (VF), which were 80-90% in control and 0-20% in 3 treated groups, with P less than 0.01-0.001. The duration of ventricular tachycardia (VT) + VF was 3.0 +/- 1.6 min in control and were 0.2 +/- 0.2, 0.2 +/- 0.1 and 1.2 +/- 2.1 min in Cys, NAC and MEA groups, respectively (with P less than 0.01-0.001). Coronary flow (CF) were remarkably reduced to about 50% during ligation in NS, but remained at normal levels in three treated groups. There were no significant protective effects on arrhythmias in CSSC and APMT perfused hearts. CF of CSSC and APMT groups were even less than those of control. The structure-activity analysis suggested that the SH group may play a crucial role in the protective effect of SH compounds on ischemia/reperfusion induced arrhythmias. The mechanism of protection was briefly discussed in this paper.
Tang
L D
LD
Department of Pharmacology, Academy of Military Medical Sciences, Beijing, China.
Tang
Z M
ZM
D000111:Acetylcysteine / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000517:prevention & control*; D003326:Coronary Circulation / Q000187:drug effects; D003543:Cysteamine / Q000627:therapeutic use*; D003545:Cysteine / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000494:pharmacology*; D017259:Dimaprit / Q000031:analogs & derivatives*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000627:therapeutic use*
D004095:Dihydropyridines; C071424:2,6-dimethyl-4-furyl-1,4-dihydropyridine-5-dicarboxylate; D003543:Cysteamine; C032887:3-aminopropyl-N'-methylisothiourea; D013890:Thiourea; D003545:Cysteine; D000111:Acetylcysteine; D017259:Dimaprit