Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts

作者：Muto Tatsuya; Usuda Haruki; Yamamura Aya; Yoshida Koji; Ohashi Ai; Mitsui Saitoh Kumiko; Sakai Junichi; Sugimoto Yumi; Mizutani Hideki; Nonogaki Tsunemasa; Hotta Yoshihiro^*

来源：Biological & Pharmaceutical Bulletin, 2014, 37(5): 731-739.

DOI：10.1248/bpb.b13-00552

• fluvoxamine
• left ventricular developed pressure
• P-31-NMR
• mitochondrial permeability transition pore (MPTP)
• ischemia-reperfusion injury
• apoptosis

Serotonin (5-hydroxytryptamine; 5-HT) is known to be activated during ischemia-reperfusion and triggers contractile dysfunction and pathological apoptosis. Here, the beneficial effects of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine was demonstrated on ischemia-reperfusion injury in guinea-pig hearts perfused using the Langendorff technique. The recovery (%) of left ventricular developed pressure (LVDP) by fluvoxamine (5x10(-8) M) was 95.4% (control: 32%), which was consistent with the inhibition of mitochondrial Ca2+([Ca2+](m)) uptake induced by changes in the Ca2+ content and acidification of the perfusate, and similar to reperfusion following global ischemia in Langendorff-perfused hearts. Fluvoxamine inhibited the increase in [Ca2+](m) induced by changes in the Ca2+ content of the perfusate in perfused preparations of mitochondria, which was similar to the results obtained with the mitochondrial permeability transition pore (MPTP) opener atractyroside. The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive cells were significantly less in fluvoxamine-treated hearts than in control hearts, with decreases in caspase-3 activity. These results suggest that SSRI inhibits opening of the MPTP by preventing [Ca2+](m) overload-induced apoptosis related to the endogenous accumulation of 5-HT in ischemia-reperfusion hearts.

• 出版日期2014-5