The Effect of Exogenous Adenosine on Functional Injury Caused by Hydrogen Peroxide in the Isolated Rat Heart

Abstract

Adenosine is an endogenous cardioprotective substance. The present study examines whether exogenous adenosine attenuates cardiac injury induced by oxida-tive stress. Rat hearts (Langendorff model) were perfused with H₂O₂ (180 μM) for 10 min, then recovered for 60 min (n = 10). In other groups adenosine 55 μM, 110 μM, or 220 μM (n = 10 in each) was given in addition to H₂O₂ throughout perfusion. Control perfusion with Krebs Henseleit only (n=7), adenosine 110 μM throughout perfusion (n = 7), and adenosine 110 μM as an intervention (n = 7) was performed. The hearts were paced at 320 beats/min. Left ventricular systolic (LVSP) and end-diastolic (LVEDP) pressures were measured together with coronary flow (CF), and left ventricular developed pressure (LVDP = LVSP - LVEDP) was calculated. H₂O₂ decreased LVSP from 105 ± 8 to 60 ± 5 mmHg (mean ± SEM) after 10 min infusion (p<0.008). Adenosine did not attenuate the decrease of LVSP. LVEDP increased from 0 to 59 ± 10 mmHg (p<0.004) and 62 ± 11 mmHg 5 and 15 min after end of infusion of H₂O₂, respectively. Neither 55 μM nor 220 μM adenosine inhibited the H₂O₂-induced increase of LVEDP. Adenosine 110 μM attenuated the increase after 15 (15 ± 4 mmHg, p<0.004) and 25 min observation (26 ± 7 mmHg, p<0.012). Adenosine did not attenuate the reduction of LVDP. CF initially increased during infusion of H₂O₂, thereafter decreased. Hearts given adenosine had higher basal CF, and CF did not increase after H₂O₂. Control perfusion with adenosine, given throughout perfusion or as an intervention, increased CF and tended to increase LVSP. In summary, adenosine did not inhibit H202-induced depression of contractility or reduction of CF. One concentration of adenosine (110 μM) attenuated H₂O₂-induced impairment of relaxation. Exogenous adenosine does not have an important influence on functional injury caused by exogenous oxidants.

Key Words:

• Adenosine
• antioxidant
• hydrogen peroxide
• ischaemia-reperfusion
• toxic oxygen metabolites