LIDOCAINE DOES NOT PREVENT THE CALCIUM PARADOX IN RAT HEARTS - A LASER MICROPROBE MASS ANALYSIS (LAMMA) STUDY

The calcium paradox stands for the cell damage that occurs when isolat ed hearts are perfused with a Ca2+-free solution followed by perfusion with a Ca2+-containing solution. Although it is generally accepted th at a massive Ca2+ influx during the Ca2+-repletion phase is responsibl e for the cell damage, there is no consensus about what makes the hear t susceptible to the calcium paradox during the Ca2+-depletion phase. It has been suggested that the extent of the calcium paradox is primar ily determined by accumulation of Na+ during Ca2+ depletion and a subs equent accumulation of Ca2+ via reverse Na+-Ca2+ exchange during Ca2repletion. According to another theory, weakening of intercalated disc junctions during Ca2+ depletion and contracture-mediated disruption o f the cell membrane during Ca2+ repletion are responsible for the calc ium paradox. In the present study we further investigated the possible role of Na+ in the development of the calcium paradox. During Ca2+ de pletion, lidocaine was used to inhibit Na+ entry through the Na+ chann els. Isolated rat hearts were perfused with Krebs Henseleit buffer (KH ) containing 1.4 mM Ca2+ for 15 min, followed by 10 min of Ca2+-free p erfusion and 10 min of reperfusion with Ca2+. In the treated group 0.1 mM lidocaine was present throughout the experiment. At the end of eac h experiment, Ca2+ cytochemistry was performed and the intracellular C a2+ content was analyzed by laser microprobe mass analysis (LAMMA). Th e results show that during Ca2+ depletion, the intracellular Ca2+ cont ent did not change significantly. Ca2+ repletion, however, gave rise t o a full calcium paradox irrespective of the presence of lidocaine: ma ssive cell damage and Ca2+ accumulation in the mitochondria. The resul ts provide further evidence that intracellular Na+ accumulation during Ca2+ depletion is not involved in the occurrence of the calcium parad ox.