|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1993 : ¥300,000 (Direct Cost : ¥300,000)
Fiscal Year 1992 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1991 : ¥900,000 (Direct Cost : ¥900,000)
Background. Plasma atrial natriuretic peptide concentrations in patients with heart failure have been reparted to be higher than those in normal subjects and to increase as the severity of heart failure progresses. Although endogenous atrial natriuretic peptide is thought to improve the cndition of patients with heart failure by reducing preload and afterload, recent findings have indicated that a high plasma atrial natiruretic peptide level is a prognostic predictor in patients with heatr failure.
Methods and Results. To evaluate the pathophysiologic role of endogenous atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide in the pulmonary circulation, plasma atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels were determined in the main pulmonary artery and pulmonary capilary wedge region on 80 patients with chronic congestive heart failure (New Yord Heart Association functional classed II to IV).
Results. The plasma atrial na
triuretic peptide level decreased significantly from the main pulmonary artery to the pulmonary capillary wedge region, whereas the plasma cGMP level increased signifivantly from the main pulmonary artery to the pulmonary capillary wedge region. In patients with mild chronic heart failure (n=50), the plasma atrial natriuretic peptide level correlated with the cG13EA\ : MP level in the main pulmonary artery (gamma=0.71, p<0.001). The atrial natriuretic peptide extraction level, calcuated as (calculated as (Atrial natriuretic peptide in the main pulmonary artery - Atrial natriuretic peptide in the pulmonary capillary wedge region) X Cardiac output X (1- hematocrit/100) ((ng/min), also correlated with the cyclic gunosine monophosphate purodection level, calculated as (cGMP in the pumonary capillary wedge region-cGMP in the main pulmonary atrey) X Cardiac output X (1-hematocrit/100)(nmol/min.). (gamma=0.78, p<0.001).In contrast, such correlations were not found in patients with severe chronic heart failure(n=30). In those patients, the atrial natriuretic peptide extraction level was significantly higher but there was no sighificant difference in the cGMP precuction level between th two groups (mild and severe chronic heart failure). Therefore, the molar raio of cGMP production to atrial natriuretic peptide extraction in the pulmonary circulation was significantly lower in patients with severe chronic heart failure (88 (〕SY.+-.〔) 16 vs. 480 (〕SY.+-.〔) 41, p<0.001). Moreover the plasma cGMP levels increased significantly from the femoral artery to the femoral vein. Among patients with mild CHF (n=52), the plasma cGMP level correlated with the ANP level, and the calculated ANP extraction level also correlated with the calculated cGMP production in the peripheral circulation (r=0.70, p<0.001). In contrast, these correlations were not found in patients with severe CHF (n=45). Among these patients, the plasma cGMP levels seemed to reach a plateau
Conclusions. These results indicate that down-regulation of atrial natriuretic peptide receptors cupled to guanylate cyclase may occur not only in the pulmonary vascular beds but also peripheral vascular beds of patients with severe chronic heart failure. Less