Effect of cicletanine on reperfusion-induced arrhythmias and myocardial ion contents: a comparison with furosemide.
We studied the effects of cicletanine, a furopyridine antihypertensive drug, and furosemide, a loop diuretic, on ventricular arrhythmias, such as sustained ventricular fibrillation (VF) and ventricular tachycardia (VT), and myocardial ion content in Langendorff rat hearts subjected to 30 min global ischaemia then 10 min reperfusion. Myocardial Na+, K+, Ca2+ and Mg2+ concentrations were measured by washout technique and atomic absorption spectrophotometry before and after ischaemia and reperfusion. Drugs were either perfused (acute treatment) or orally gavaged daily to the rats for 14 days before isolation of their hearts (chronic treatment). Under in vitro conditions 10(-5), 3 x 10(-5), 10(-4) or 3 x 10(-4) M of cicletanine reduced the incidence of sustained VF and VT from the control values of 91% and 100% to 83% and 100%, 50% (P less than 0.05) and 67%, 33% (P less than 0.01) and 50% (P less than 0.05), 25% (P less than 0.01) and 41% (P less than 0.05), respectively. Chronic treatment with 3, 10, 30 or 100 mg.kg-1.day-1 of cicletanine also resulted in a dose-dependent anti-arrhythmic effect. Neither acute (10(-5), 3 x 10(-5) and 10(-4) M) nor chronic furosemide treatment (3, 10 and 30 mg.kg-1.day-1) influenced the incidence of arrhythmias. Acute treatment with cicletanine or furosemide did not change myocardial ion concentrations, in non-ischaemic hearts, while chronic treatment with 30 mg.kg-1.day-1 furosemide significantly reduced myocardial Na+, K+ and Mg2+ content and increased Ca2+ concentration. Both acute and chronic cicletanine treatments attenuated ischaemia/reperfusion-induced myocardial Na+ and Ca2+ gains and K+ loss, while furosemide did not.(ABSTRACT TRUNCATED AT 250 WORDS)
Koltai
M
M
Institut Henri Beaufour, Paris, France.
Tosaki
A
A
Berthet
P
P
Tarrade
T
T
Esanu
A
A
Braquet
P
P
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D001834:Body Water; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004573:Electrolytes / Q000032:analysis*; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects*; D009206:Myocardium / Q000737:chemistry*; D011725:Pyridines; D051381:Rats; D011921:Rats, Inbred WKY
D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D004573:Electrolytes; D011725:Pyridines; D005665:Furosemide; C038068:cicletanine