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Sir,—It has been well documented that neurohormonal mediators, such as the renin–angiotensin system,1 endothelin,2 and brain natriuretic peptide (BNP),3 are severely activated in patients with congestive heart failure, and that the circulating concentrations of these mediators are good predictors of the severity of congestive heart failure and the prognosis. It has also been demonstrated that both angiotensin II and endothelin-1, like BNP, are locally expressed in cardiac tissue.4-6 It is not clear, however, whether the increase in plasma concentrations of angiotensin II and endothelin-1 is caused by increased expression and spillover from cardiac tissue in patients with heart disease. To address this question, we measured the plasma concentrations of angiotensin II, endothelin-1, and BNP in blood withdrawn from both coronary sinus and ascending aorta in five patients subject to cardiac catheterisation.
All patients were studied in the morning and in a fasting state. Informed consent was obtained from each patient before the study. Coronary sinus blood was sampled using a 6 or 7 F catheter inserted via the right femoral vein. The position of the tip of the catheter was confirmed fluoroscopically and by blood oxygen saturation (mean (SD) 41 (3)%). Arterial blood was withdrawn using a 6 F pigtail catheter positioned in the ascending aorta adjacent to the coronary ostia, which was inserted via the femoral artery. Care was taken to use the same amount of time for drawing arterial blood samples as for the coronary sinus blood sampling. The blood samples were transferred to test tubes containing EDTA that were precooled with ice, and centrifuged immediately after at 1000 g for 10 minutes at 4°C. The plasma was stored at −20°C until analysis. The plasma concentrations of angiotensin II, endothelin-1, and BNP were determined by radioimmunoassay.
Table 1 shows the clinical characteristics, haemodynamic and echocardiographic data, and plasma concentrations of angiotensin II, endothelin-1, and BNP in both coronary sinus and ascending aorta. Patient 1, who had the most severe congestive heart failure among the five patients studied, had the highest plasma concentrations of angiotensin II, endothelin-1, and BNP in both the coronary sinus and ascending aorta. The plasma concentrations of angiotensin II and endothelin-1 in the coronary sinus were lower than or equal to those in the ascending aorta in all patients. In contrast, the plasma concentration of BNP was apparently higher in the coronary sinus than in the ascending aorta in all patients. The differences in BNP concentrations between the coronary sinus and ascending aorta were more prominent in patients with higher BNP concentrations in the ascending aorta with the exception of patient 2, who had remarkable pulmonary hypertension.
These results suggest that, even though all three neurohormonal mediators appear to be good predictors of the severity of heart failure, the circulating concentrations of angiotensin II and endothelin-1 do not predominantly derive from cardiac tissue (unlike BNP, which predominantly derives from myocardium). Further investigation with a larger number of patients is needed to confirm this conclusion.