Endothelial control of lower limb blood flow in chronic heart failure.

Abstract

Background-Limitation of the blood supply to skeletal muscle in chronic heart failure may contribute to the symptoms of fatigue and diminished exercise capacity. The pathophysiology underlying this abnormality is not known. The purpose of this study was to assess the effect of endothelium dependent and independent vasodilator agents on blood flow in the leg of patients with heart failure. Methods and results-Blood flow in the leg was measured in patients with heart failure (n = 20) and compared with that in patients with ischaemic heart disease and normal left ventricular function (n = 16) and patients with chest pain and normal coronary arteries (n = 8). External iliac artery blood flow was measured using intravascular Doppler ultrasound and quantitative angiography. Flow was recorded at rest and in response to bolus doses of the endothelium independent vasodilator, papaverine. Endothelium dependent responses were measured by infusion of acetylcholine and substance P. Mean (SEM) baseline blood flow was reduced at rest (2-9 (0-4) v 4 5 (0.3) mVs, P < 0 001) and vascular resistance was raised (37.4 (3.6) v 27'1 (3.0) units, P < 0.05) in patients with heart failure compared with that in controls. The peak blood flow response to papaverine (8 mg), acetylcholine (10-7-10-5 moIl), and substance P (5 pmollmin) was reduced in heart failure, with greater impairment of the response to acetylcholine than substance P. There was a correlation between baseline blood flow in the heart failure group and diuretic dose (r = -0-62, P = 0 003), New York Heart Association classification (r = -0 65, P = 0.002), and left ventricular ejection fraction (r = 0-80, P = 0.0004). Conclusions-There is reduced blood flow and raised vascular resistance at rest in the legs of patients with heart failure. The degree of impaired blood flow in the leg correlates with the severity of heart failure. There is impairment of the response to both endothelium dependent and independent vasodilators. Abnormal function of the vascular myocyte in heart failure may explain these results as would structural abnormalities of the resistance vessels. (Heart 1996;75:469-476)

The intramuscular contribution to the slow oxygen uptake kinetics during exercise in chronic heart failure is related to the severity of the condition

“…This, in turn, would necessitate a greater substrate-level phosphorylation during the protracted exercise transient (27) and contribute to increased intramuscular accumulation of fatigue-related metabolites such as ADP, inorganic phosphate, and hydrogen ions. The CHF syndrome induces many changes in the control of regional skeletal muscle blood flow that could predispose to a limitation in O 2 flux on transition to and during exercise (30,33,43,54,63,65). In the present study, a shear stress-induced release of vasodilatory substances (e.g., nitric oxide, acetylcholine, adenosine, bradykinin, prostaglandins, and interstitial K ϩ ) (39) during bout 1 may have facilitated a better microvascular matching of O 2 delivery to utilization in bout 2 (47), the resulting increase in oxygenation being associated with speeded V O 2 kinetics.…”

Contribution of Nitric Oxide to Reactive Hyperemia

“…37,38 A 0.018-in Doppler flow wire (Cardiometrics, Inc) was introduced through the catheter and positioned 1 cm beyond the catheter tip to obtain an adequate flow velocity signal. Thus, the drug infusions were given downstream of the flow wire.…”

The TNF-α/Sphingosine-1-Phosphate Signaling Axis Drives Myogenic Responsiveness in Heart Failure

“…TPR is, indeed, elevated in HF patients [3,5], albeit at the expense of tissue perfusion (which is inversely proportional to vascular resistance). At early stages of HF, this reduction in tissue perfusion, although counterintuitive based on its potential to compromise organ viability, is well tolerated on the organ level.…”

“…This has widespread clinical consequences [11] including: (i) compromised cerebral blood flow [12], possibly explaining the HF-associated decrements in higher order brain function (i.e. memory loss, reduced executive function, psychomotor slowing) [13,14], (ii) reduced kidney perfusion [15] resulting in decreased serum sodium and increased serum creatinine [16,17,18] and (iii) inhibited skeletal muscle blood flow [3,5] leading to altered skeletal muscle structure and function [19]. Importantly, these findings establish impaired organ perfusion as a possible link between HF-associated TPR increases and poor outcome and mortality in HF patients.…”