Effects of Na+/H+ exchange inhibitors on myocardial derangements induced by hydrogen peroxide in the isolated perfused rat heart

• Published in: Japanese Journal of Pharmacology 1998, Vol.76 (suppl.2), p.279-279
• Main Authors: Hara, Akiyoshi, Arakawa, Johji, Hashizume, Hiroko, Abiko, Yasushi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)41227-4

Reactive oxygen species, including hydrogen peroxide (H_2 O_2 ), have been demonstrated to contribute to production of the isehemia-reperfusion damage in the heart. Recently, Na^+ /H^+ exchange inhibitors, such as 5-(N,N-dimetyl)amioride (DMA) and KB-R9032 (KBR), are shown to protect the myocardium from the isehemia-reperfusion damage. The present study was carried out to determine whether DMA and KBR attenuate the H_2 O_2 -induced mechanical and metabolic derangements in the isolated rat heart, which was perfused aerobically at a constant flow rate and driven electrically. H_2 O_2 (600μM) decreased the left ventricular developed pressure and increased the left ventricular end diastolic pressure in the heart (i.e., mechanical dysfunction), and decreased the tissue levels of high-energy phosphates (ATP and ADP) (i.e., metabolic change), and increased the tissue level of malondialdehyde (i.e., lipid peroxidation). These mechanical and metabolic alterations induced by H_2 O_2 were attenuated by DMA (15μM) and KBR (5μM). Nevertheless, neither DMA nor KBR modified the tissue malondialdehyde level, which was increased by H_2 O_2 . These results suggest that inhibition of the Na^+ /H^+ exchange system is effective in attenuating the H_2 O_2 -induced mechanical and metabolic derangements in the heart.