OBJECTIVETo evaluate the change of endothelin-1 (ET-1) in the mini-swine model of acute myocardial infarction (AMI) and reperfusion and the effect of Tongxinluo (TXL) on it, and to explore the possible mechanism of no-reflow.

METHODSForty mini-swines were randomized into 5 groups: the model group, the small,middle and large dose of TXL groups and the sham-operated group, 8 in each group. The AMI reperfusion model was established by coronary ligation for 3 hrs followed with relaxation for 1 hr. Plasma ET-1 content before and after AMI, and after reperfusion was determined respectively by radioimmunoassay. The ET-1 mRNA expression in myocardial tissue of normal, ischemic and no-reflow area were respectively quantified by reverse transcription-polymerase chain reaction.

RESULTS(1) Compared with before AMI, levels of plasma ET-1 at the time points of 5 min and 3 hrs after AMI, 5 min and 1 hrs after reperfusion in the model group were significantly raised, showing an increasing tendency (all P < 0.01). But the increment in the middle and large dose of TXL groups were all lower than that in the model group (P < 0.05). (2) In the model and the TXL groups, levels of ET-1 in myocardial tissue of ischemic and no-reflow area were significantly higher than those in the normal area, and the increment in no-reflow area was higher than that in ischemic area (all P < 0.01). Compared with the model group, significant lowering of ET-1 in ischemic area was only shown in the middle and large dose of TXL groups (P < 0.01). (3) In the model and the TXL groups, ET-1 mRNA expression in ischemic area was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01).

CONCLUSIONThe endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells. was significantly higher (all P < 0.01), while it in no-reflow area was significantly lower than that in the normal area respectively (all P < 0.01). The raised ET-1 mRNA expression in the middle and large dose TXL groups was significantly lowered when compared with that in the model group (P < 0.01). Conclusion The endothelium injury might be one of the important mechanisms for no-reflow phenomenon. TXL might reduce the no-reflow by protecting endothelium cells.