Background: The association between B- type natriuretic peptide ( BNP) and coronary artery disease is not fully understood. Objective: To assess whether ischaemia per se is a stimulus for BNP secretion. Setting: University tertiary hospital, Spain ( Virgen de la Arrixaca). Design: Prospective interventional study. Patients: 11 patients ( 55 ( 9) years, left ventricular ejection fraction ( LVEF) 45% ( 7%) with a non- complicated anterior myocardial infarction ( MI) and isolated stenosis of the left anterior descending ( LAD) coronary artery, successfully treated by primary angioplasty. Interventions: 11.0 ( 0.9) days after MI, the LAD was occluded ( 20 min) for intracoronary infusion of progenitor cells. Blood samples were obtained from the femoral artery ( peripheral circulation ( PC)) and the coronary sinus ( coronary circulation ( CC)) immediately before and after coronary occlusion. Main outcome measures: BNP ( pg/ ml) was measured and ischaemia biomarkers were monitored. Results: During coronary occlusion, all patients experienced transitory chest pain and ST- segment dynamic changes. After coronary occlusion, lactic acid levels rose in CC ( 1.42 ( 0.63) - 1.78 ( 0.68) ng/ ml, p = 0.003). Myoglobin and cardiac troponin T did not differ in CC or PC at 24 h. No differences were found in LVEF (+ 0.18% ( 2.4)%, p = 0.86) and motion score index ( - 0.02 ( 0.06), p = 0.37). Before occlusion, BNP levels did not differ significantly in CC versus PC ( 253 ( 56) vs 179 ( 34), p = 0.093). After occlusion, BNP showed a significant increase in CC ( vs 332 ( 61), p = 0.004), but no change occurred in PC ( vs 177 ( 23), p = 0.93), and circulating BNP levels were higher in CC versus PC ( p = 0.008). Conclusions: In response to acute ischaemia, BNP levels immediately increase in coronary sinus but not at the peripheral level. BNP release in the coronary effluent may exert local beneficial effects.