Cyclosporin-A reduces leukocyte accumulation and protects against myocardial ischaemia reperfusion injury in rats

Francesco Squadrito, Domenica Altavilla, Giovanni Squadrito, Antonino Saitta, Giuseppe M. Campo, Mariarita Arlotta, Cristina Quartarone, Marcella Ferlito, Achille P. Caputi

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was designed to evaluate the effect of cyclosporin A in a rat model of myocardial ischaemia reperfusion injury (MI/R). Anaesthetized rats were subjected to total occlusion (20 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), serum tumor necrosis factor (TNF-α), cardiac mRNA for TNF-α, cardiac intercellular adhesion molecule-1 (ICAM-1) immunostaining and myocardial contractility (left ventricle dP/dt(max)) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity and myeloperoxidase activity (a marker of leukocyte accumulation) both in the area-at-risk and in the necrotic area, reduced myocardial contractility and induced a marked increase in the serum levels of the TNF-α. Furthermore increased cardiac mRNA for TNF-α was measurable within 10 to 20 min of left main coronary artery occlusion in the area-at-risk and increased levels were generally sustained for 0.5 h. Finally, myocardial ischaemia-reperfusion injury increased ICAM-1 staining in the myocardium. Administration of cyclosporin A (0.25, 0.5 and 1 mg/kg as an i.v. infusion 5 min after coronary artery occlusion) lowered myocardial necrosis and myeloperoxidase activity in the area-at-risk and in the necrotic area, decreased serum CPK activity, increased myocardial contractility, reduced serum levels of TNF-α and the cardiac cytokine mRNA levels, and blunted ICAM-1 immunostaining in the injured myocardium. The data suggest that cyclosporin A suppresses leukocyte accumulation and protects against myocardial ischaemia-reperfusion injury. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalEuropean Journal of Pharmacology
Volume364
Issue number2-3
DOIs
StatePublished - Jan 8 1999

Keywords

  • Cyclosporin A
  • Myocardial ischemia
  • TNF-α (tumor necrosis factor-α)

ASJC Scopus subject areas

  • Pharmacology

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