CARDIOPROTECTIVE POTENCY OF THE RADICAL SCAVENGER S-2-(3 AMINOPROPYLAMINO) ETHYLPHOSPHOROTHIOIC ACID IN THE POSTISCHEMIC 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 dr 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. The administration of WR-2721 (0.5 mmol/kg body weight) led in situ to an accelerated restoration of contractile activity in the post-ligated left ventricular area reflected by the post-ischaemic recovery of SSLC (64 +/- 10% of pre-ischaemic values compared with 27 +/- 6% in control animals 60 min following reperfusion; p < 0.02). The present data confirm an effective reduction in the exposure of the reperfused heart to endogenously released free radicals by WR-2721, a partial preservation of high-energy phosphates and an improvement in post-ischaemic contractility and encourage further investigation of such favourable action in injured myocardium.