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Ann Thorac Surg 1995;60:377-381
© 1995 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Inhibition of Na⁺/H⁺ Exchanger Attenuates Neutrophil-Mediated Reperfusion Injury

First Department of Surgery, Osaka University Medical School, Osaka, Japan

Accepted for publication March 31, 1995.

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.

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