Cardioprotective effects of the calcineurin inhibitor FK506 and the PAF receptor antagonist and free radical scavenger, EGb 761, in isolated ischemic/reperfused rat hearts

David D. Haines, I. Bak, P. Ferdinándy, Fadia F. Mahmoud, Saleh A. Al-Harbi, Ingolf E. Blasig, A. Tósaki

Research output: Contribution to journalArticle

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Abstract

Effects of the calcineurin inhibitor FK506, the platelet-activating factor (PAF) antagonist, and free radical scavenger Ginkgo biloba extract, EGb 761, and their combination on reperfusion-induced ventricular fibrillation (VF), ventricular tachycardia (VT), and recovery of cardiac function were studied after 30 min of global ischemia followed by 2 h of reperfusion in isolated rat hearts. In the first series of studies, rats received a daily (oral) dose of 0, 1, 5, 10, 20, or 40 mg/kg/day FK506 for 10 days. FK506 dose-dependently reduced the incidence of reperfusion-induced total (irreversible plus reversible) VF from a value of 92% for untreated animals to 92% (NS), 83% (NS), 67% (NS), 33% (p <0.05), and 25% (p <0.05), for doses of 1-40 mg/kg/day, respectively, with effects on incidence of VT showing the same pattern. FK506, between 20 and 40 mg/kg/day, also resulted in significant recovery of postischemic cardiac function. In the second series of studies, rats were treated with EGb 761 alone or in combination with FK506. Whereas no significant reduction in arrhythmias or improvement in cardiac function resulted from a single intervention of EGb 761 at 25 mg/kg/day, combined treatment of rats with 25 mg/kg/day of EGb 761 and 1 or 5 mg/kg/day of FK506 resulted in a reduction in total and irreversible VF of 92% and 92% to 42% (p <0.05) and 33% (p <0.05), 25% (p <0.05) and 8% (p <0.05), respectively, versus untreated control animals, paralleled by similar effects on the incidence of VT and accompanied by significant improvements in postischemic cardiac function. Our results demonstrate a novel cardioprotective characteristic of FK506 and suggest that combination therapy by using FK506 plus EGb 761 synergistically improves postischemic cardiac function, while reducing the incidence of reperfusion-induced VF and VT, which may expand the clinical utility of FK506 and allow therapy with FK506 at lower doses than are currently useful.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume35
Issue number1
DOIs
Publication statusPublished - 2000

Fingerprint

Free Radical Scavengers
Tacrolimus
Ventricular Fibrillation
Ventricular Tachycardia
Reperfusion
Incidence
Ginkgo biloba extract 761
platelet activating factor receptor
Calcineurin Inhibitors
Platelet Activating Factor
Recovery of Function
Cardiac Arrhythmias
Ischemia

Keywords

  • Arrhythmias
  • Cardiac function
  • EGb 761
  • FK506
  • Isolated heart
  • Rat
  • Reperfusion

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Cardioprotective effects of the calcineurin inhibitor FK506 and the PAF receptor antagonist and free radical scavenger, EGb 761, in isolated ischemic/reperfused rat hearts. / Haines, David D.; Bak, I.; Ferdinándy, P.; Mahmoud, Fadia F.; Al-Harbi, Saleh A.; Blasig, Ingolf E.; Tósaki, A.

In: Journal of Cardiovascular Pharmacology, Vol. 35, No. 1, 2000, p. 37-44.

Research output: Contribution to journalArticle

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