Effect of cicletanine on reperfusion-induced arrhythmias and ion shifts in isolated rat hearts.
Isolated hearts from normotensive (NT) and spontaneously hypertensive (SH) rats, subjected to normothermic global ischemia, were used to study whether cicletanine (a new antihypertensive drug) treatment exerts an antiarrhythmic effect against reperfusion-induced arrhythmias. The effect of the drug on myocardial ion contents (Na+, K+, Ca2+, and Mg2+) during ischemia and reperfusion was also determined. Using the optimal doses of cicletanine (30 and 100 mg/kg orally for 14 days), the incidence of reperfusion-induced ventricular fibrillation (VF) and ventricular tachycardia (VT) was reduced from their control values of 91 and 100% (after 30 min of ischemia) to 41 (p less than 0.05), 50 (p less than 0.05) and 41 (p less than 0.05), 58% in the NT group, while the corresponding value in the SH group for VF and VT were 17 (p less than 0.001), 33 (p less than 0.01) and 17 (p less than 0.001), 25% (p less than 0.001), respectively. The results obtained indicate that the cardioprotective effect of cicletanine was greater in the SH group than in the NT group. Cicletanine significantly reduced the ischemia- and reperfusion-induced myocardial Na+ and Ca2+ gains and inhibited the loss of myocardial K+ and Mg2+ in both NT and SH groups. The antiarrhythmic effect of cicletanine appears to be correlated with the preservation of myocardial Na+, K+, Ca2+, and Mg2+ contents via an ion transport modulation.
Institut Henri Beaufour, Le Plessis Robinson, France.
A
A
Tosaki
M
M
Koltai
D A
DA
Willoughby
P
P
Braquet
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011725:Pyridines; D051381:Rats; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism
D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D011725:Pyridines; D012964:Sodium; C038068:cicletanine; D008274:Magnesium; D011188:Potassium; D002118:Calcium