Cicletanine and reperfusion injury: is there any correlation between arrhythmias, 6-keto-PGF1 alpha, thromboxane B2, and myocardial ion shifts (Na+, K+, Ca2+, and Mg2+) induced by ischemia/reperfusion in isolated rat heart.
We studied the effects of cicletanine, an anti-hypertensive drug, on reperfusion arrhythmias in relation to 6-keto-PGF1 alpha, thromboxane B2 (TXB2), and ion shifts (Na+, K+, Ca2+, and Mg2+) induced by ischemia and reperfusion in hearts isolated from spontaneously hypertensive rats. Hearts were subjected to 30-min global ischemia followed by 10-min reperfusion. 6-keto-PGF1 alpha and TXB2 concentrations were determined by radioimmunoassay (RIA) from coronary effluents, and myocardial Na+, K+, Ca2+, and Mg2+ contents were measured by atomic absorption spectrophotometry from myocardial tissue. Two basic protocols were used: (a) acute administration when 3, 10, 30, or 100 mg/L cicletanine was included in the perfusion buffer; and (b) chronic application, in which rats received cicletanine 3, 10, 30, or 100 mg/kg/day orally for 14 days. Acute administration of the drug in low concentrations (3 or 10 mg/L), significantly increased endogenous 6-keto-PGF1 alpha production before ischemia and during reperfusion, whereas higher doses of cicletanine (30 or 100 mg/L) as well as chronic application of the drug failed to increase production of 6-keto-PGF1 alpha in the myocardium. TXB2 production was not influenced by either acute or chronic treatment with the drug. Neither treatment changed myocardial ion contents in comparison with control values (Na+ = 45 +/- 4, K+ = 252 +/- 7, Ca2+ = 1.4 +/- 0.1, and Mg2+ = 12.5 +/- 0.3 mmol/kg dry weight) in nonischemic hearts. Thirty-minute ischemia resulted in a two- and fourfold accumulation of myocardial Na+ and Ca2+ and a 50% decrease in both K+ and Mg2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Tosaki
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A
Institut Henri Beaufour, Les Ulis, France.
Hellegouarch
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Braquet
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P
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents; D001834:Body Water / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism* / Q000503:physiopathology; D004232:Diuretics / Q000494:pharmacology*; D004562:Electrocardiography; D066298:In Vitro Techniques; D008274:Magnesium / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D011725:Pyridines; D051381:Rats; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*
D000889:Anti-Arrhythmia Agents; D004232:Diuretics; D011725:Pyridines; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D012964:Sodium; C038068:cicletanine; D008274:Magnesium; D011188:Potassium; D002118:Calcium