Adrenergically mediated coronary vasoconstriction in patients with Syndrome X

Summary

Several studies have shown that coronary vasodilator reserve is impaired in some patients with chest pain and angiographically normal coronary arteries. In a subgroup of these patients, who additionally show ST depression on the electrocardiogram during exercise and are generally labelled as having Syndrome X, the impairment of coronary flow reserve is associated with metabolic and functional signs consistent with an increased sympathetic drive. The aim of the present investigation was to ascertain whether the impairment of coronary vasodilator reserve in patients with Syndrome X is due to adrenergically mediated vasoconstriction of coronary microcirculation. Myocardial blood flow (MBF), at baseline and following intravenous infusion of dipyridamole (0.56 mg/kg over 4 minutes), was measured by means of¹³N-ammonia and dynamic positron emission tomography in 10 females (mean age 52±8 years) with a chest pain history, ST-segment depression during exercise, and angiographically normal coronaries. The first MBF study was performed while the patients were off therapy; a repeat MBF study was performed following 1 week of treatment with the alpha-1 blocker doxazosin (2 mg/day). Off therapy MBF was 1.13±0.25 ml/min/g at baseline and increased to 2.35±0.66 ml/min/g following dipyridamole. Coronary vasodilator reserve (dipyridamole/baseline MBF) was 2.18±0.56. During treatment with doxazosin, baseline MBF was not different from the control value (1.25±0.50 ml/min/g), while added dipyridamole significantly increased MBF to 3.52±1.20 ml/min/g (p<0.01 vs. off therapy). Coronary vasodilator reserve was significantly increased (2.91±0.92, p<0.01 vs. control value) by doxazosin. This study indicates that alpha-1 adrenoceptors might play a role in the reduction of coronary reserve in patients with Syndrome X. Further clinical studies are needed to ascertain the efficacy of alpha-1 blockers for the treatment of such patients.