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

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 (beta-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 microM 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.
AuthorsJ W Lee, H Miyawaki, E V Bobst, J D Hester, M Ashraf, A M Bobst
JournalJournal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 31 Issue 1 Pg. 113-21 (Jan 1999) ISSN: 0022-2828 [Print] ENGLAND
PMID10072720 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Cyclic N-Oxides
  • Fluorescent Dyes
  • Reactive Oxygen Species
  • Rose Bengal
  • Nitric Oxide
  • Ethanol
  • Mannitol
  • Histidine
  • Carnosine
  • Sodium Azide
  • TEMPO
Topics
  • Animals
  • Carnosine (therapeutic use)
  • Coronary Vessels (drug effects)
  • Cyclic N-Oxides (analysis)
  • Dose-Response Relationship, Drug
  • Ethanol (pharmacology)
  • Fluorescent Dyes (analysis)
  • Heart Rate (drug effects)
  • Histidine (therapeutic use)
  • Magnetic Resonance Spectroscopy
  • Male
  • Mannitol (pharmacology)
  • Myocardium (chemistry)
  • Nitric Oxide (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (metabolism)
  • Recovery of Function
  • Reperfusion Injury (therapy)
  • Rose Bengal (analysis)
  • Sodium Azide (pharmacology)
  • Time Factors
  • Ventricular Function, Left (drug effects)

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