Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia.
BACKGROUND
Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown.


METHODS
Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR).


RESULTS
Left ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size.


CONCLUSIONS
NHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.
Toyoda
Y
Y
Division of Cardiothoracic Surgery and Biometrics Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA.
Khan
S
S
Chen
W
W
Parker
R A
RA
Levitsky
S
S
McCully
J D
JD
D000818:Animals; D002314:Cardioplegic Solutions; D003326:Coronary Circulation; D006146:Guanidines / Q000494:pharmacology; D006324:Heart Arrest, Induced; D006439:Hemodynamics; D066298:In Vitro Techniques; D008274:Magnesium; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D011188:Potassium; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology*; D013450:Sulfones / Q000494:pharmacology; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D002314:Cardioplegic Solutions; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C093373:cariporide; D008274:Magnesium; D011188:Potassium