EFFECTS OF SPECIFIC SODIUM HYDROGEN EXCHANGE INHIBITOR DURING CARDIOPLEGIC ARREST/

Background. The accumulation of intracellular sodium during myocardial ischemia couples an inappropriate calcium influx and depressed cardia c recovery during subsequent reperfusion. The effects of the selective sodium/hydrogen exchange inhibitor HOE 694 are evaluated during myoca rdial ischemia and reperfusion. Methods. Ten isolated rat hearts were subjected to a 2-minute infusion of St. Thomas' cardioplegia +/- 1 mu mol/L HOE 694 followed by 50 minutes' normothermic (37 degrees C) glob al ischemia. Intracellular sodium accumulation was continuously measur ed using triple quantum filtered Na-23 nuclear magnetic resonance spec troscopy without chemical shift reagents. Hemodynamic variables were a ssessed before and after ischemia, Results. The addition of 1 mu mol/L HOE 694 to St. Thomas' cardioplegic solution (n = 5) attenuated the a ccumulation of intracellular sodium after 50 minutes' ischemia (160.5% +/- 9.1% versus 203.4% +/- 10.9% [mean +/- standard error] HOE 694 ve rsus control, respectively; p = 0.014) and after the initial reperfusi on period (first 30 minutes) (258.7% +/- 10.2% versus 335.9% +/- 10.3% ; p = 0.008). HOE 694-treated hearts showed significantly improved pos tischemic recovery of left ventricular developed pressure (53.5% +/- 8 .4% versus 26.4% +/- 6.6%; p = 0.036) and rate-pressure product (40.2% +/- 6.9% versus 13.2% +/- 5%; p = 0.014). Postischemic recovery of co ronary flow was not significantly different between the two groups (68 .6% +/- 5.9% versus 55.5% +/- 4.6%, HOE 694 versus control, respective ly; p = 0.11). Conclusions. The addition of 1 mu mol/L HOE 694 to card ioplegic solution attenuates the increase of intracellular sodium duri ng myocardial ischemia and early reperfusion. This is coupled with an improved recovery of contractile function, possibly as a result of dec reased sodium and calcium overload of ischemic myocardium.