Na+/H+ exchange inhibition with cardioplegia reduces cytosolic [Ca2+] and myocardial damage after cold ischemia

Cold cardioplegia protects against reperfusion damage. Blocking Na+/H+ exchange may be as protective as cardioplegia by improving the left ventricular pressure (LVP)-[Ca2+] relationship after cold ischemia. In guinea pig isolated hearts subjected to cold ischemia (4 h, 17degreesC) and reperfusion, the cardioprotective effects of a Krebs-Ringer (KR) solution, a cardioplegia solution, a KR solution containing the Na+/H+ exchange inhibitor eniporide (1 muM), and a cardioplegia solution containing eniporide were compared. Treatments were given before and initially after cold ischemia. Systolic and diastolic [Ca2+] were calculated from indo-1 fluorescence transients recorded at the LV free wall. During ischemia, diastolic [Ca2+] increased in each group but more so in the KR group. Peak systolic and diastolic [Ca2+] on initial reperfusion were highest after KR and smallest after cardioplegia + eniporide. After reperfusion, systolic-diastolic LVP (% of baseline) and infarct size (%), respectively, were KR, 47+/-3%, 37+/-4%; cardioplegia, 71+/-5%*, 20+/-2.2%*; KR + eniporide, 73+/-5%*, 11+/-3%*dagger; and cardioplegia + eniporide 77+/-3%*, 10+/-1.4%*dagger (*Pless than or equal to0.05 vs KR;dagger Pless than or equal to0.05 vs cardioplegia). Ca2+ overload was reduced in each treated group, and most in the cardioplegia + eniporide group, and was associated with the improved function. Inhibition of Na+/H+ exchange was as effective as cardioplegia in restoring function and better than cardioplegia in reducing infarct size after hypothermic ischemia. The combination of cardioplegia and Na+/H+ exchange inhibition did not produce additive protective effects but caused a larger decrease in Ca2+ loading.