Improved functional recovery of ischemic rat hearts due to singlet oxygen scavengers histidine and carnosine

John W. Lee, Hiroshi Miyawaki, Elizabeth V. Bobst, Jeff D. Hester, Muhammad Ashraf, Albert M. Bobst

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

There is increasing evidence that reactive oxygen species (ROS) contribute to post-ischemic reperfusion injury, but determination of the specific ROS involved has proven elusive. In the present study electron paramagnetic resonance (EPR) spectroscopy was used in vitro to measure the relative quenching of singlet oxygen (1O2) by histidine and carnosine (β-alanyl-L-histidine) utilizing the hindered secondary amine 2,2,6,6-tetramethyl-4-piperidone HCl (4-oxo-TEMP). The relative effect of histidine and carnosine on functional recovery of isolated perfused rat hearts was also studied. Functional recovery was measured by left ventricular developed pressure (LVDP), first derivative of left ventricular pressure (dP/dt), heart rate (HR) and coronary flow (CF). EPR measurements and Stern-Volmer plots showed that 400 μM carnosine quenched 1O2 twice as effectively as equimolar histidine in vitro. Moreover, 10 mM histidine improved functional recovery of isolated rat hearts significantly more than 1 mM histidine. Furthermore, 1 mM carnosine improved functional recovery significantly more than equimolar histidine and as effectively as 10 mM histidine. Experiments with 1 mM mannitol, a known hydroxyl radical scavenger, did not show an improvement in functional recovery relative to control hearts, thereby decreasing the likelihood that hydroxyl radicals are the major damaging species. On the other hand, the correlation between improved functional recovery of isolated rat hearts with histidine and carnosine and their relative 1O2 quenching effectiveness in vitro provides indirect evidence for 1O2 as ROS participating in reperfusion injury.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of molecular and cellular cardiology
Volume31
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Keywords

  • Carnosine
  • EPR
  • Histidine
  • Ischemia-reperfusion injury
  • Singlet oxygen

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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