The contribution of Na+/H+ exchange to ischemia-reperfusion injury after hypothermic cardioplegic arrest.
BACKGROUND
Na+/H+ exchange has been reported to be one of the key mechanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood.


METHODS
Sodium-propionate-induced cell swelling, an indicator of the function of the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Langendorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recovery of cardiac function after hypothermic ischemia. This was done using FR168888, an inhibitor of Na+/H+ exchange.


RESULTS
In the in vitro study, rat lymphocytes were observed to swell at 17 degrees, 22 degrees, and 27 degrees C, indicating that the Na+/H+ exchanger remains functional even under hypothermic conditions. FR168888 was found to significantly inhibit Na+/H+ exchange-induced cell swelling, even at 17 degrees C. In the in vivo study, pretreatment with FR168888 was found to prevent the deterioration of ventricular function, even after 5 hours of hypothermic cardioplegic arrest. This was associated with a decrease in the reperfusion-induced elevation in resting tension.


CONCLUSIONS
These results suggest that Na+/H+ exchange in the heart still occurs, even under hypothermic conditions, and contributes to reperfusion injury, even after hypothermic cardioplegic arrest.
Yamauchi
T
T
Department of Organ Transplantation, Osaka University Medical School, Japan.
Ichikawa
H
H
Sawa
Y
Y
Fukushima
N
N
Kagisaki
K
K
Maeda
K
K
Matsuda
H
H
Shirakura
R
R
D000818:Animals; D048429:Cell Size / Q000502:physiology; D006324:Heart Arrest, Induced; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013696:Temperature
D011422:Propionates; D017923:Sodium-Hydrogen Exchangers; C514135:sodium propionate; C029658:propionic acid