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, dimethylamiloride, on myocardial injury after 1 h global ischaemia and 30 min. reperfusion in the isolated arterially perfused interventricular septum of the rabbit heart. After ischaemia and reperfusion challenge, dimethylamiloride significantly 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 vitro model supported functional maintenance of physiologically-like conditions. Where myocardial portions were submitted to ischaemic conditions and reperfusion, myocyte cell damage reached usual characteristics of infarct-like induced lesions. Intracellular oedema, severe disruption of myofibrils with loss of muscle striation and both swelling and fragmentation of mitochondria were the main characteristics observed. Dimethylamiloride treatment clearly modifies ultrastructural findings towards the normalization of cell shape and structure, only a slight-middle intracellular oedema and contraction bands were found. On the basis of the present results, we suggest that the protective effects exhibited by dimethylamiloride on the ischaemic myocardium 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.
Salinas
P
P
Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain.
Gil-Loyzaga
P
P
Barrigon
S
S
D000584:Amiloride / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006346:Heart Septum / Q000187:drug effects* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D010477:Perfusion; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D000584:Amiloride