Effects of endothelin-1 and endothelin-A receptor antagonist on recovery after hypothermic cardioplegic ischemia in neonatal lamb hearts

T. Hiramatsu, J. Forbess, T. Miura, S. J. Roth, M. A. Cioffi, J. E. Mayer

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Background: Prior studies suggest an important role for coronary endothelium in ischemia/reperfusion (I/R) injury. Decreased endothelial release of the vasodilator nitric oxide occurs after I/R, but the role of the endothelium-derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown. Methods and Results: We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10°C cardioplegic ischemia and examined the effects of ET- 1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts. ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of reperfusion in 8 control hearts were constant (2.2±1.2 fmol/L, 2.2±1.3 fmol/L, and 2.5±1.0 fmol/L, respectively). In group 2 (n=6), 10 μmol/L of BE-18257B was given just before reperfusion. In group 3 (n=8), 10 pmol/L ET-1 was given just before the start of reperfusion. At 30 minutes of reperfusion, the ET-A antagonist hearts had significantly greater recovery of LV systolic (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt), coronary blood flow (CBF), and MV̇O2 compared with controls (P<.05). The ET-1 hearts showed significantly reduced recovery of LV systolic (positive maximum and volume- normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF, and myocardial oxygen consumption compared with controls (P<.05). Conclusions: These results, combined with prior studies, suggest that I/R causes reduced production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the vasoconstriction that is caused by the continued presence of ET-1. This imbalance may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic agents in reducing the injury that results from I/R.

Original languageEnglish (US)
Pages (from-to)II400-II404
JournalCirculation
Volume92
Issue number9 SUPPL.
StatePublished - Jan 1 1995

Keywords

  • endothelin
  • ischemia
  • reperfusion

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Hiramatsu, T., Forbess, J., Miura, T., Roth, S. J., Cioffi, M. A., & Mayer, J. E. (1995). Effects of endothelin-1 and endothelin-A receptor antagonist on recovery after hypothermic cardioplegic ischemia in neonatal lamb hearts. Circulation, 92(9 SUPPL.), II400-II404.