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  • Title: Na+/H+ exchange inhibition with cardioplegia reduces cytosolic [Ca2+] and myocardial damage after cold ischemia.
    Author: Camara AK, An J, Chen Q, Novalija E, Varadarajan SG, Schelling P, Stowe DF.
    Journal: J Cardiovasc Pharmacol; 2003 May; 41(5):686-98. PubMed ID: 12717098.
    Abstract:
    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, 17 degrees C) 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 microM), 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 (*P </= 0.05 vs KR; dagger P </= 0.05 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.
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