Reduced cardiac extraction of norepinephrine and epinephrine in patients with heart failure--correlation with left ventricular function.

To assess whether the impairment of neuronal norepinephrine (NE) uptake is involved in the increased NE release observed in the failing heart, we examined the cardiac extractions of NE and epinephrine (E) and their correlation with left ventricular function in 16 patients with anterior transmural old myocardial infarction (OMI) and 18 patients with dilated cardiomyopathy (DCM). The plasma NE and E levels were both increased in OMI and DCM, particularly in the coronary sinus, as compared with those in 16 control subjects (Control). The cardiac NE and E extractions were significantly reduced in OMI (P < 0.001) and in DCM (P < 0.001) as compared with those in the Control (NE: -38 +/- 36% in OMI, -33 +/- 28% in DCM, and 14 +/- 18% in Control; E: 30 +/- 12% in OMI, 32 +/- 17% in DCM, and 54 +/- 8% in Control). However, there was no reduction in the NE and E extraction in the leg in OMI and DCM. Cardiac NE and E extractions both showed significant correlation with the left ventricular ejection fraction (r = 0.685, P < 0.001 and r = 0.609, P < 0.001, respectively). We conclude that, in patients with heart failure, NE release from the heart is increased partially due to the reduction of the cardiac neuronal uptake of NE which is proportional to the severity of left ventricular dysfunction.