期刊
BASIC RESEARCH IN CARDIOLOGY
卷 96, 期 5, 页码 454-462出版社
DR DIETRICH STEINKOPFF VERLAG
DOI: 10.1007/s003950170027
关键词
ischaemia/reperfusion injury; cardioprotection; endothelin; neutrophils; pig
It has previously been shown that endothelin (ET) receptor antagonists limit myocardial ischaemia/reperfusion (I/R) injury. The mech anism behind this effect is still unclear. The aim of this study was to elucidate the possible relationship between cardioprotection by an ETA receptor antagonist and inhibition of neutrophil accumulation or activation in the myocardium determined as myeloperoxidase (MPO) activity during I/R. Anaesthetised pigs were subjected to 45 min ischaemia by ligation of the left anterior descending coronary artery (LAD) followed by 4 h of reperfusion. Infiltration of MPO-containing cells, presumably neutrophils, into the ischaemic area was confirmed with an immunohistochemical technique using antibodies against porcine MPO. Vehicle (n = 7) or the selective ETA receptor antagonist LU 135252 (LU; n = 7) were given into the LAD during the last 10 min of ischaemia and the first 5 min of reperfusion. There were no significant differences in LAD flow, mean arterial pressure, heart rate, or rate pressure product between the groups during I/R. The area at risk was similar in the two groups. LU reduced the final infarct size to 40 +/- 6 % of the area at risk compared to 80 +/- 6 % in the vehicle group (P < 0.001). Endothelin-like immunoreactivity increased 2-fold in the ischaemic area in the vehicle group (P < 0.01), but not in the group given LU. MPO activity was higher (2.5x) in the ischaemic than in the non-ischaemic myocardium of the vehicle group. The MPO activity in the ischaemic myocardium was significantly lower in the group given LU (7.0 +/- 1.2 units g(-1)) than in the vehicle group (14.2 +/- 1.9 units g(-1); P < 0.01). There was a significant correlation between the infarct size and MPO activity (P < 0.01, r = 0.68). In conclusion, local administration of the selective ETA receptor antagonist LU during the last period of ischaemia and early reperfusion reduces the extent of myocardial necrosis and MPO activity. This suggests that LU may exert its cardioprotective effect by inhibiting neutrophil-mediated injury.
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