Urinary excretion of biopyrrins, oxidative metabolites of bilirubin, increases after spasm provocation tests in patients with coronary spastic angina

Background: Bilirubin apparently functions as an antioxidant in vivo by reacting with reactive oxygen species, and, as a result, becomes oxidized. The urinary excretion of oxidative metabolites of bilirubin, biopyrrins, could be a biological marker for in vivo production of reactive oxygen species. The purpose of this study was to examine the extent of oxidative stress in patients with possible ischemic heart diseases (n=44) by measuring urinary biopyrrins by enzyme-linked immunosorbent assay before and after the spasm provocation test (SPT). Methods: Spot urine samples were collected five times; 1 day before, in the morning just before, immediately after, 6 h after, and 1 day after the SPT. Nineteen patients were positive to SPT judged from the specific changes in electrocardiogram for myocardial ischemia following intracoronary injections of ergonovine. Results: The baseline data such as age, sex, number of risk factors and concentrations of serum bilirubin, and the measured hemodynamic parameters of heart rate, blood pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction were not different between the positive and negative groups. The baseline concentrations of biopyrrins during the control period were not significantly different between the two groups. However, they increased significantly after the SPT, thereby the magnitude of increases immediately after and 6 h after the SPT were significantly (P<0.001 and P<0.01, respectively) greater in the positive group than in the negative. Conclusion: The present findings strongly suggest that coronary arterial occlusion augments production of biopyrrins, which indicates exposure to oxidative stress in patients with ischemic heart diseases.