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

Abstract

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 ETA receptor antagonist, in 80 patients. All patients were randomly allocated to an intracoronary infusion of saline or BQ-123 (6 μmol/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 ETA 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.