Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Regular Articles
Protective Effects of Fluvoxamine against Ischemia/Reperfusion Injury in Isolated, Perfused Guinea-Pig Hearts
Tatsuya MutoHaruki UsudaAya YamamuraKoji YoshidaAi OhashiKumiko Mitsui-SaitohJunichi SakaiYumi SugimotoHideki MizutaniTsunemasa NonogakiYoshihiro Hotta
Author information
JOURNAL FREE ACCESS FULL-TEXT HTML

2014 Volume 37 Issue 5 Pages 731-739

Details
Abstract

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 (5×10−8 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.

Content from these authors
© 2014 The Pharmaceutical Society of Japan
Previous article Next article
feedback
Top