704-4 EDRF-mediated Increases in Conduit Artery Distensibility are Impaired in Chronic Heart Failure

Chronic heart failure (CHF) is associated with reduced EDRF activity in resistance arteries. A similar effect in conduit arteries would reduce their distensibility and increase the load on the compromised heart. We measured pulse wave velocity (PWV), inversely related to distensibility, in the right common iliac artery (RCIA) during acetylcholine (ACh, endothelium-dependent dilator) and adenosine (Ado, endothelium-independent dilator) infusion in 6 patients with CHF (NYHA grades 2–3, EF < 40%, age 50 ± 16 [SD] years, 4 men) and 9 normal subjects (N) (age 49 ± 6 years, 4 men). CHF was due to dilated cardiomyopathy (with normal blood pressure, cholesterol, glucose, and coronary angiograms). PWV, measured from the pressure pulse delay between 2 transducers 5 cm apart, was measured during infusions proximal (P) and distal (D)to the RCIA segment studied. We corrected for BP and other downstream effects by subtracting D from P effects. At baseline, PWV was similar in the two groups (CHF 8.7 ± 1.1; N 9.1 ± 1.5 ms-1). ACh (10-7, 10-6, 10-5mol/L) induced dose-dependent reductions in PWV (-5, -15, -25%) in normals but no change (+ 2, +2, -3%) in CHF (p = 0.0013). Ado (2 × 10-7, 2 × 10-6,2 × 10-5mol/L) induced similar dose-related reductions in PWV in N (-5, -12, -24%) and in CHF (-1, -12, -14%, NS). These data indicate that conduit artery distensibility is increased by ACh-stimulated EDRF activity in normal subjects but not in patients with CHF. This suggests that physiological EDRF-mediated increases in distensibility, as occur during exercise, may be impaired in CHF despite normal resting distensibility