EFFECT OF NA-REPERFUSED RAT HEARTS( REDUCTION AND MONENSIN ON ION CONTENT AND CONTRACTILE RESPONSE IN NORMOXIC AND ISCHEMIC)

The possibility was explored whether the functional properties of Na+/ Ca2+ exchange are altered after ischaemia, thereby contributing to the elevated intracellular (i) Ca2+ levels in ischaemic reperfused hearts . The intracellular Na+, K+ and Ca2+ contents in rat Langendorff heart preparations were determined by atomic absorption spectrometry under normoxic conditions, after ischaemia (30 min) and after ischaemia (30 min) plus reperfusion (30 min). In addition, the influence of modulati ng the Na+ gradient (Na-0(+)/Na-i(+)) across the sarcolemma was studie d with respect to cardiac contractility and intracellular ion content. This was done by either decreasing extracellular (0) Na+ or by increa sing Na-i(+) with monensin, both in normoxic and reperfused hearts. Bo th Na-0(+) reduction and monensin led to an increase in contractility and coronary flow, an effect which was nearly abolished in reperfused hearts. Under normoxic conditions the intracellular ion contents amoun ted to Na+=12.4+/-0.4, K+=99.0+/-3.1 and Ca2+=0.64+/-0.02 mmol/kg cell (means+/-SEM, n=7). In normoxic hearts, lowering Na-0(+) reduced and monensin increased Na-i(+), thereby both leading to a decrease in Nagradient; no effect on total Ca-i(2+) content was observed. Na-i(+) in creased twofold after ischaemia as compared to the normoxic situation, an effect which was aggravated (4 fold increase) in reperfused hearts . The opposite effects were observed for K-i(+) with a 25% decrease af ter ischaemia and a 40% decrease in reperfused hearts. Only after isch aemia plus reperfusion was Ca-i(2+) increased (6 fold). In reperfused hearts, lowering Na-0(+) again reduced and monensin increased Na-i(+), whereas a further rise in Ca-i(2+) was now observed depending on the Na+ gradient across the sarcolemma: the larger the drop in Na+ gradien t, the more pronounced the increase in Ca-i(2+) in the reperfused hear t. We conclude that the Ca-i(2+) increase in reperfused hearts can be modulated by changing the Na+ gradient across the sarcolemma. This sug gests that inhibited or reversed Na+/Ca2+ exchange is predominantly re sponsible for the rise in Ca-i(2+) in ischaemic hearts that are subjec ted to reperfusion.