| Abstrakt: |
Objective: R 75 231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection by R 75 231 may be explained if it can be shown that endogenous adenosine plays a role in catecholamine cardiotoxicity and if nucleoside transport inhibition is required for the cardioprotective effect of R 75 231. Methods: Several groups of rabbits were infused with catecholamines until death. Changes in survival with time of infusion by coinfusion of aminophylline and/or treatment with R 75 231 and its two stereoenantiomers were assessed. Results: Treatment with R 75 231 postponed the time to reach 50% mortality threefold after challenge with adrenaline or noradrenaline. Draflazine, the (-)-enantiomer of R 75 231, was also effective, whereas the (+)-enantiomer, which is devoid of any effect on the transporter, was not cardioprotective. The cardioprotective effect of R 75 231 was dependent on the extent and duration of ex vivo inhibition of the transporter in blood. Co-infusion of aminophylline with adrenaline significantly accelerated the rate of mortality. Conclusions: Nucleoside transport inhibition is the major, if not the only, determinant for efficacy of R 75 231 and draflazine as cardioprotective agents. Taken together with the evidence for a role of endogenous adenosine, the benefit from nucleoside transport inhibition in this model may be the result of prolonged accumulation of endogenous adenosine.Cardiovascular Research 1993;27:111-115 [ABSTRACT FROM PUBLISHER] |
