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, 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.
Camara
Amadou K S
AK
Anesthesiology Research Laboratories, Department of Anesthesiology, Cardiovascular Research Center, The Medical College of Wisconsin, Veterans Affairs Medical Center, Milwaukee, Wisconsin, USA.
An
Jianzhong
J
Chen
Qun
Q
Novalija
Enis
E
Varadarajan
Srinivasan G
SG
Schelling
Pierre
P
Stowe
David F
DF
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D006146:Guanidines / Q000627:therapeutic use*; D006168:Guinea Pigs; D006324:Heart Arrest, Induced; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000378:metabolism; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013450:Sulfones / Q000627:therapeutic use*; D017725:Ventricular Pressure / Q000187:drug effects
D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C118397:eniporide; D002118:Calcium