THE ROLE OF NA-H+ EXCHANGE OCCURRING DURING HYPOXIA IN THE GENESIS OFREOXYGENATION-INDUCED MYOCARDIAL EDEMA()

To investigate the role of Na+-H+ exchange occurring during hypoxia in the genesis of reoxygenation-induced myocardial oedema, isolated perf used rat hearts were submitted to 40 min of hypoxia and 90 min of reox ygenation, The influence of three factors on myocardial water content was analysed according to a 2 x 2 x 2 factorial design; the hearts wer e perfused at either pH = 7.4 or pH = 7.0, with either HCO3- buffer or HCO3--free HEPES buffer, and in half of the experiments the hypoxic b uffer contained HOE642 6. 7 mu mol/l. In an additional group, 160 min of normoxia resulted in no lactate dehydrogenase (LDH) release and in a 35.8% increase in myocardial water, independently of pH and of the p resence of HCO, in the buffer, In hearts perfused at pH = 7.4, reoxyge nation induced LDH release which was reduced (P < 0.05) by HOE642 by 2 0.1%, by HCO3--free perfusion by 57.5%, and by the combination of both by 91.2%. Reoxygenation also induced severe myocardial oedema (26.3% increase (P < 0.05) respect to normoxia), HOE642 reduced (P < 0.05) re oxygenation oedema by 15.7%, HCO3--free perfusion by 8.9%, and the com bination of both by 24.6%. The effects of HCO3--free perfusion could b e mimicked in HCO3- perfused hearts by blocking Na+-HCO3- cotransport with 4-4'-dibenzanidostilbene-2,2'-disulphonic acid (DIDS). The benefi cial and additive effects of HOE642 and of HCO3--free perfusion on oed ema were not a mere consequence of their protective effects against th e oxygen paradox, since they were observed in groups perfused at pH = 7.0, a condition which virtually prevented LDH release without prevent ing oedema (19.0% increase in myocardial water), Thus, reoxygenation-i nduced myocardial oedema may occur in the absence of necrosis, and is largely determined by Na+ gain during hypoxia via Na+-H+ exchange and Na+-HCO3- cotransport. (C) 1997 Academic Press Limited.