Cicletanine and reperfusion injury: Is there any correlation between arrhythmias, 6-keto-PGFthromboxane B2 and myocardial ion shifts (Na2+K2+Ca2+and MG2+) induced by ischemia/reperfusion in isolated rat heart

A. Tósaki, Anne Hellegouarch, Pierre Braquel

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11 Citations (Scopus)

Abstract

We studied the effects of cicletanine, an anti-hypertensive drug, on reperfusion arrhythmas in relation to 6-keto-PGFthromboxane B, (TXB2), 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-PGFand TXB2 concentrations were determined by radioimmunoassay (RIA) from coronary effluents, and myocardial Na+ K+Ca2+and Mg2+ contents were measured by atomic absorption spectrophotometry fron 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), signilicantly increased endogenous 6 keto-PGF production before ischemia and during reperfusion, whereas higher doses of cicletanine (30 or 100 mg 1 as well as chronic application of the drug failed to increase production of 6-keto-PGF in the myocardium. TXB, 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. Ca 1.4 ± 0.1 and Mg 12.5 ± 0.3 mmol kg dry weight) in nonischenlic hearts. Thirty-minute ischemia resulted in it a two-and fourtold accumulation of myocardial Na+ and Ca2+ a 50 decrease in both K and Mg2+. After 10-min reperfusion myocardial ion contents were similar to the values of 30 min ischemia, and all hearts showed fibrillation in the unteated group. Both acute and chronic administration of cicletanine protected the heart against reperfusion arrhythmias and ion shifts (30 and 100 mg I. or mg kg day). Although the data we report do not show any correlation between the antiarrhythmic effect of cicletanine and 6-keto-PGFrelease, they do indicate a close correlation between antiarrhythmic activity of the drug and myocardial ion shifts induced by ischemia and reperfusion. Our results indicate that cletanine is able to modify the ischemia- and reperfusion induced deleterious ion shifts and consequently to protect the heart against life-threatening arrhythmia.

Original languageEnglish
Pages (from-to)551-559
Number of pages9
JournalJournal of Cardiovascular Pharmacology
Volume17
Issue number4
Publication statusPublished - 1991

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Reperfusion Injury
Reperfusion
Cardiac Arrhythmias
Ischemia
Ions
Pharmaceutical Preparations
Atomic Spectrophotometry
Myocardial Reperfusion
Anti-Arrhythmia Agents
Inbred SHR Rats
cicletanine
Antihypertensive Agents
Radioimmunoassay
Myocardium
Buffers
Perfusion
Weights and Measures

Keywords

  • 6-keto-PGF
  • Arrhythmia
  • Cicletanine
  • Myocardial Na
  • Rat heart
  • Reperfusion
  • Thromboxane B

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

@article{902bf43c35b64cd9ade4be176014b8eb,
title = "Cicletanine and reperfusion injury: Is there any correlation between arrhythmias, 6-keto-PGF1αthromboxane B2 and myocardial ion shifts (Na2+K2+Ca2+and MG2+) induced by ischemia/reperfusion in isolated rat heart",
abstract = "We studied the effects of cicletanine, an anti-hypertensive drug, on reperfusion arrhythmas in relation to 6-keto-PGF1αthromboxane B, (TXB2), 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-PGF1αand TXB2 concentrations were determined by radioimmunoassay (RIA) from coronary effluents, and myocardial Na+ K+Ca2+and Mg2+ contents were measured by atomic absorption spectrophotometry fron 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), signilicantly increased endogenous 6 keto-PGF1α production before ischemia and during reperfusion, whereas higher doses of cicletanine (30 or 100 mg 1 as well as chronic application of the drug failed to increase production of 6-keto-PGF1α in the myocardium. TXB, 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. Ca 1.4 ± 0.1 and Mg 12.5 ± 0.3 mmol kg dry weight) in nonischenlic hearts. Thirty-minute ischemia resulted in it a two-and fourtold accumulation of myocardial Na+ and Ca2+ a 50 decrease in both K and Mg2+. After 10-min reperfusion myocardial ion contents were similar to the values of 30 min ischemia, and all hearts showed fibrillation in the unteated group. Both acute and chronic administration of cicletanine protected the heart against reperfusion arrhythmias and ion shifts (30 and 100 mg I. or mg kg day). Although the data we report do not show any correlation between the antiarrhythmic effect of cicletanine and 6-keto-PGF1αrelease, they do indicate a close correlation between antiarrhythmic activity of the drug and myocardial ion shifts induced by ischemia and reperfusion. Our results indicate that cletanine is able to modify the ischemia- and reperfusion induced deleterious ion shifts and consequently to protect the heart against life-threatening arrhythmia.",
keywords = "6-keto-PGF, Arrhythmia, Cicletanine, Myocardial Na, Rat heart, Reperfusion, Thromboxane B",
author = "A. T{\'o}saki and Anne Hellegouarch and Pierre Braquel",
year = "1991",
language = "English",
volume = "17",
pages = "551--559",
journal = "Journal of Cardiovascular Pharmacology",
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publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - Cicletanine and reperfusion injury

T2 - Is there any correlation between arrhythmias, 6-keto-PGF1αthromboxane B2 and myocardial ion shifts (Na2+K2+Ca2+and MG2+) induced by ischemia/reperfusion in isolated rat heart

AU - Tósaki, A.

AU - Hellegouarch, Anne

AU - Braquel, Pierre

PY - 1991

Y1 - 1991

N2 - We studied the effects of cicletanine, an anti-hypertensive drug, on reperfusion arrhythmas in relation to 6-keto-PGF1αthromboxane B, (TXB2), 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-PGF1αand TXB2 concentrations were determined by radioimmunoassay (RIA) from coronary effluents, and myocardial Na+ K+Ca2+and Mg2+ contents were measured by atomic absorption spectrophotometry fron 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), signilicantly increased endogenous 6 keto-PGF1α production before ischemia and during reperfusion, whereas higher doses of cicletanine (30 or 100 mg 1 as well as chronic application of the drug failed to increase production of 6-keto-PGF1α in the myocardium. TXB, 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. Ca 1.4 ± 0.1 and Mg 12.5 ± 0.3 mmol kg dry weight) in nonischenlic hearts. Thirty-minute ischemia resulted in it a two-and fourtold accumulation of myocardial Na+ and Ca2+ a 50 decrease in both K and Mg2+. After 10-min reperfusion myocardial ion contents were similar to the values of 30 min ischemia, and all hearts showed fibrillation in the unteated group. Both acute and chronic administration of cicletanine protected the heart against reperfusion arrhythmias and ion shifts (30 and 100 mg I. or mg kg day). Although the data we report do not show any correlation between the antiarrhythmic effect of cicletanine and 6-keto-PGF1αrelease, they do indicate a close correlation between antiarrhythmic activity of the drug and myocardial ion shifts induced by ischemia and reperfusion. Our results indicate that cletanine is able to modify the ischemia- and reperfusion induced deleterious ion shifts and consequently to protect the heart against life-threatening arrhythmia.

AB - We studied the effects of cicletanine, an anti-hypertensive drug, on reperfusion arrhythmas in relation to 6-keto-PGF1αthromboxane B, (TXB2), 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-PGF1αand TXB2 concentrations were determined by radioimmunoassay (RIA) from coronary effluents, and myocardial Na+ K+Ca2+and Mg2+ contents were measured by atomic absorption spectrophotometry fron 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), signilicantly increased endogenous 6 keto-PGF1α production before ischemia and during reperfusion, whereas higher doses of cicletanine (30 or 100 mg 1 as well as chronic application of the drug failed to increase production of 6-keto-PGF1α in the myocardium. TXB, 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. Ca 1.4 ± 0.1 and Mg 12.5 ± 0.3 mmol kg dry weight) in nonischenlic hearts. Thirty-minute ischemia resulted in it a two-and fourtold accumulation of myocardial Na+ and Ca2+ a 50 decrease in both K and Mg2+. After 10-min reperfusion myocardial ion contents were similar to the values of 30 min ischemia, and all hearts showed fibrillation in the unteated group. Both acute and chronic administration of cicletanine protected the heart against reperfusion arrhythmias and ion shifts (30 and 100 mg I. or mg kg day). Although the data we report do not show any correlation between the antiarrhythmic effect of cicletanine and 6-keto-PGF1αrelease, they do indicate a close correlation between antiarrhythmic activity of the drug and myocardial ion shifts induced by ischemia and reperfusion. Our results indicate that cletanine is able to modify the ischemia- and reperfusion induced deleterious ion shifts and consequently to protect the heart against life-threatening arrhythmia.

KW - 6-keto-PGF

KW - Arrhythmia

KW - Cicletanine

KW - Myocardial Na

KW - Rat heart

KW - Reperfusion

KW - Thromboxane B

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