Studies on the role of sodium/hydrogen exchange system in myocardial ischemia-reperfusion injury.
This study aimed at the exploration of the relationship between Na(+)-H+ exchange system and myocardial ischemia-reperfusion injury (MRI) in an attempt to provide a theoretic basis for the prevention and treatment of MRI. We used the isolated working guinea pig hearts as the experimental model to mimick cardiopulmonary bypass, which included 120 min hypothermic ischemic cardioplegic arrest followed by 60 min normothermic reperfusion. The hearts were divided into 2 groups: the control group receiving St. Thomas' Hospital Solution (STS) and the treated group receiving STS + amiloride, a Na(+)-H+ exchange blocker. The results showed that during reperfusion, [Na+]i and [Ca2+]i overloads, poor recovery of cardiac function, increases in CPK release and OFR generation, reduction of ATP content and serious damage of ultrastructure were seen in group 1; whereas there were no [Na+]i and [Ca2+]i overloads and better recovery of cardiac function accompanied by improved results of biochemical assay and less damage of ultrastructure was found in group 2. Our study indicates that amiloride can inhibit Na(+)-H+ exchange system in cardiac cells during early reperfusion period, which prevents [Na+]i overload produced by Na(+)-H+ exchange, and stops Na(+)-Ca2+ exchange activated by high level of [Na+]i, thus attenuating [Ca2+]i overload caused by Na(+)-Ca2+ exchange and myocardial injury. Therefore, we conclude that Na(+)-H+ exchange blocker, amiloride, can exert significant protective effects on MRI and its use may prove to be a new clinical approach to prevention and cure of MRI.
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Department of Cardiovascular Surgery, Affiliated Hospital, Hainan Medical College, Haikou.
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D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002315:Cardiopulmonary Bypass; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D016623:Ion Pumps; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D011897:Random Allocation; D015222:Sodium Channels / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*
D015220:Calcium Channels; D016623:Ion Pumps; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride