FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in rats.
The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent 30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg(-1), 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 +/- 16 and 149 +/- 23 pg mg(-1) protein, respectively), compared with that of the saline-treated group (258 +/- 27 pg mg(-1) protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83+0.19 unit g(-1) weight of tissue in the saline-treated group to 0.36 +/- 0.09 and 0.33 +/- 0.06 unit g(-1) weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg(-1), respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 +/- 1.5,13.5 +/- 1.9% at 1.0 and 3.2 mg kg(-1)), compared with 22.2+2.7% in the saline-treated group. These results suggestthat IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.
Ohara
F
F
Department of Cardiovascular Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co, Ltd, Osaka, Japan. fumihiro_ohara@po.fujisawa.co.jp
Ohkubo
K
K
Maeda
K
K
Seki
J
J
Goto
T
T
D000818:Animals; D003864:Depression, Chemical; D004195:Disease Models, Animal; D006146:Guanidines / Q000627:therapeutic use*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors*; D013876:Thiophenes / Q000627:therapeutic use*
C449400:FR 183998; D006146:Guanidines; D016209:Interleukin-8; D017923:Sodium-Hydrogen Exchangers; D013876:Thiophenes; D009195:Peroxidase