Acute endothelin-A receptor antagonism prevents normal reduction of myocardial ischemia on repeated balloon inflations during angioplasty.

BACKGROUND Myocardial ischemia and reperfusion are associated with increased production of endothelin (ET)-1. METHODS AND RESULTS We examined the effects of BQ-123, a selective ET(A) receptor antagonist, in 80 patients. All patients were randomly allocated to an intracoronary infusion of saline or BQ-123 (6 micromol/L over 20 minutes). The reference group consisted of 20 patients undergoing coronary angiography. BQ-123 produced a 10% (P:<0.005) increase in distal coronary artery diameter. The main study group consisted of 30 patients undergoing coronary angioplasty. All patients underwent a minimum of 3 balloon inflations (BIs). Surface and intracoronary electrocardiographic ST-segment shift as well as pain score were recorded at the end of each BI. BQ-123 or saline was given by intracoronary infusion between the second and the third BI in random allocation. In the saline group, intracoronary ST-elevation decreased from 1.26+/-0.55 mV during the first BI to 0.77+/-0.56 mV during the third BI (P:<0.05) and the surface ST elevation decreased from 0.20+/-0.15 to 0.10+/-0.07 mV (P:<0.05). In the BQ-123 group, the respective values were 1.22+/-0.48 mV and 1.13+/-0.62 mV (intracoronary) and 0.17+/-0.18 and 0.17+/-0.21 mV (surface) (both P:=NS). The decrease in pain score was significantly higher in the saline group (F:=5.97, P:=0.004). In 30 patients (collateral circulation group), the angioplasty protocol was repeated with the use of a pressure guide wire. BQ-123 produced a significant (F:=3.30, P:=0.04) decrease in coronary wedge pressure. CONCLUSIONS Acute ET(A) receptor antagonism prevents the normal reduction of myocardial ischemia on repeated BIs during angioplasty. This may be explained by a "steal" effect through coronary collaterals.