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 suggest that IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats.