Inhibition of Na+/H+ exchanger attenuates neutrophil-mediated reperfusion injury.
BACKGROUND
The effect of Na+/H+ exchange inhibition in neutrophil-induced reperfusion injury was investigated using a new amiloride analogue, 5-methyl-N-isobutyl amiloride (MIA).


METHODS
Rat neutrophils were separated using Percoll gradient. Luminol chemiluminescence intensity of isolated neutrophils was depressed by MIA in a dose-dependent manner.


RESULTS
The effect of MIA on neutrophil-induced reperfusion injury was evaluated in Langendorff-perfused rat hearts subjected to 30 minutes of normothermic ischemia. Postischemic left ventricular developed pressure recovery was depressed by the reperfusion with neutrophils (60% +/- 7% to 33% +/- 26%) and was reverted by MIA pretreatment (86% +/- 17%, p < 0.05). MIA also improved percent recovery of coronary flow (51% +/- 2% to 70% +/- 13%), reduced creatine kinase (0.28 +/- 0.1 to 0.085 +/- 0.03 IU.L-1.g-1 dry wt), and lactate dehydrogenase leakage (10.6 +/- 3.8 to 5.16 +/- 1.3 IU.L-1.g-1 dry wt) significantly. The incidence of reperfusion-induced ventricular fibrillation also was reduced by MIA.


CONCLUSIONS
The inhibition of Na+/H+ exchange shows a protective effect against neutrophil-induced reperfusion injury possibly by inhibiting the activation of neutrophils.
Faes
F C
FC
First Department of Surgery, Osaka University Medical School, Japan.
Sawa
Y
Y
Ichikawa
H
H
Shimazaki
Y
Y
Ohashi
T
T
Fukuda
H
H
Shirakura
R
R
Matsuda
H
H
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D008163:Luminescent Measurements; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D018375:Neutrophil Activation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; C056369:5-(N-methyl-N-isobutyl)amiloride