Inhibitory effect of a hydrophilic αtocopherol analogue, MDL 74, 405, on generation of free radicals in stunned myocardium in dogs

Xian Liang Tang, Paul B. Mccay, Jian Zhong Sun, Craig J. Hartley, Margo Schleman, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

A previous study has demonstrated that the hydrophilic (αtocopherol analogue, MDL 74, 405, attenuates postischemic myocardial dysfunction ("stunning" in dogs. The present study was undertaken to determine directly whether the salutary effect of this drug on myocardial stunning results from inhibition of the generation of oxygen-derived free radicals. Open-chest dogs undergoing a 15-min coronary artery occlusion and 3 h of reperfusion received an intravenous infusion of either saline (controls, n = 7) or MDL 74, 405 (n = 6) starting 30 min before coronary occlusion and ending 60 min after reflow at a dose of 0.3 mg/kg/h. To measure free radical production, all dogs received an intravenous infusion of the spin trap αphenyl N-tert-butyl nitrone (PBN) and local coronary venous plasma was analyzed by electron paramagnetic resonance (EPR). In control dogs, the myocardial production of PBN adducts exhibited an initial burst immediately after the onset of reflow and remained elevated until 10 min after reperfusion. Dogs treated with MDL 74, 405 demonstrated a marked decrease in PBN adduct production. This effect of MDL 74, 405 could not be attributed to nonspecific factors such as differences in ischemic zone size, collateral flow, arterial pressure, heart rate, coronary flow or other hemodynamic variables. These results demonstrate that the hydrophilic vitamin E analogue, MDL 74, 405, inhibits free radical generation after myocardial ischemia-reperfusion in vivo. This finding provides direct evidence that the salutary effects of MDL 74, 405 on myocardial stunning are due to attenuation of oxidative stress.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalFree Radical Research
Volume22
Issue number4
DOIs
StatePublished - 1995
Externally publishedYes

Fingerprint

Myocardial Stunning
Tocopherols
Free Radicals
Dogs
Coronary Occlusion
Intravenous Infusions
Reperfusion
Myocardial Reperfusion
Oxidative stress
Electron Spin Resonance Spectroscopy
Hemodynamics
Vitamin E
Myocardial Ischemia
Paramagnetic resonance
MDL 73404
Coronary Vessels
Arterial Pressure
Oxidative Stress
Thorax
Heart Rate

Keywords

  • Free radical generation
  • Hydrophilic αtocopherol analogue
  • Myocardial stunning
  • Open-chest dogs

ASJC Scopus subject areas

  • Biochemistry

Cite this

Inhibitory effect of a hydrophilic αtocopherol analogue, MDL 74, 405, on generation of free radicals in stunned myocardium in dogs. / Tang, Xian Liang; Mccay, Paul B.; Sun, Jian Zhong; Hartley, Craig J.; Schleman, Margo; Bolli, Roberto.

In: Free Radical Research, Vol. 22, No. 4, 1995, p. 293-302.

Research output: Contribution to journalArticle

Tang, Xian Liang ; Mccay, Paul B. ; Sun, Jian Zhong ; Hartley, Craig J. ; Schleman, Margo ; Bolli, Roberto. / Inhibitory effect of a hydrophilic αtocopherol analogue, MDL 74, 405, on generation of free radicals in stunned myocardium in dogs. In: Free Radical Research. 1995 ; Vol. 22, No. 4. pp. 293-302.
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