Cardioprotective potency of the radical scavenger S-2-(3 aminopropylamino) ethylphosphorothioic acid in the post-ischaemic rat heart.
S-2-(3 aminopropylamino) ethylphosphorothioic acid (WR-2721) shown to surpass radical scavenging thiols in their radioprotective efficacy in cancer-type diseases has been tested for its protective potential in the reperfused heart. We investigated the radical scavenger properties of the compound in a radical generating system in vitro as well as in isolated rat hearts subjected to 30 min ischaemia and 30 min reperfusion with the electron-paramagnetic resonance spin trap technique. The action on high-energy phosphates is observed by means of phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy while its influence on left ventricular systolic segmental length change (SSLC) during 60 min reperfusion following 60 min regional ischaemia was assessed with a fibreoptic system in anaesthetized open-chest rats. WR-2721 (0.1 mM) reduced the vascular concentration of radical adduct in isolated hearts by up to 78% (275 +/- 84% of pre-ischaemic baseline values vs 1260 +/- 413%, p < 0.05) between 5 and 12.5 min reperfusion. This was accompanied by a reduction of the left ventricular end diastolic pressure to pre-ischaemic values at 30 min of reperfusion (9 +/- 6 mmHg vs 42 +/- 8 mmHg in the absence of WR-2721, p < 0.02). An accelerated recovery of creatine phosphate levels (78 +/- 5% of pre-ischaemia values vs 41 +/- 5% within 60 min reperfusion: p < 0.05) was observed under similar conditions with NMR-spectroscopy, although the post-ischaemic tissue content of adenosine triphosphate was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Pissarek
M
M
Research Institute of Molecular Pharmacology, Berlin, Germany.
Jänichen
F
F
Blasig
I E
IE
Haseloff
R
R
Keller
T
T
Tapp
E
E
Krause
E G
EG
D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D004734:Energy Metabolism / Q000187:drug effects; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D010758:Phosphorus; D051381:Rats; D017208:Rats, Wistar
D016166:Free Radical Scavengers; D010758:Phosphorus; D004999:Amifostine