Ultrastructural evidence of the protective effect of Na+/H+ exchange inhibition on the in vitro damage induced by ischaemia reperfusion in the interventricular septum of the rabbit heart

We investigated the effects of the Na+/H+ antiporter inhibitor, dimethylami loride, on myocardial injury after I h global ischaemia and 30 min. reperfu sion in the isolated arterially perfused interventricular septum of the rab bit heart. After ischaemia and reperfusion challenge, dimethylamiloride sig nificantly increased the recovery of developed tension in a dose-dependent manner, and significantly decreased the maximal increase in resting tension . Ultrastructural analysis of myocytes submitted to the experimental in vit ro model supported functional maintenance of physiologically-like condition s. Where myocardial portions were submitted to ischaemic conditions and rep erfusion, myocyte cell damage reached usual characteristics of infarct-like induced lesions. Intracellular oedema, severe disruption of myofibrils wit h loss of muscle striation and both swelling and fragmentation of mitochond ria were the main characteristics observed. Dimethylamiloride treatment cle arly modifies ultrastructural findings towards the normalization of cell sh ape and structure, only a slight-middle intracellular oedema and contractio n bands were found. On the basis of the present results, we suggest that th e protective effects exhibited by dimethylamiloride on the ischaemic myocar dium are compatible with its Na+/ H+ antiporter inhibition properties, they diminish Na+ accumulation and then either Ca2+ overload or non-exocytotic noradrenaline release during the ischaemia and reperfusion challenge.