Group III/IV muscle afferents impair limb blood in patients with chronic heart failure.

OBJECTIVE: To better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise. METHODS: Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27 ± 3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing µ-opioid receptor-sensitive muscle afferents. RESULTS: Cardiac-output (Q) and femoral blood-flow (QL) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8-13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p<0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10-14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p<0.05). CONCLUSION/PRACTICE/IMPLICATIONS: Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.

Understanding exercise-induced hyperemia: central and peripheral hemodynamic responses to passive limb movement in heart transplant recipients.

To better characterize the contribution of both central and peripheral mechanisms to passive limb movement-induced hyperemia, we studied nine recent (<2 yr) heart transplant (HTx) recipients (56 ± 4 yr) and nine healthy controls (58 ± 5 yr). Measurements of heart rate (HR), stroke volume (SV), cardiac output (CO), and femoral artery blood flow were recorded during passive knee extension. Peripheral vascular function was assessed using brachial artery flow-mediated dilation (FMD). During passive limb movement, the HTx recipients lacked an HR response (0 ± 0 beats/min, Δ0%) but displayed a significant increase in CO (0.4 ± 0.1 l/min, Δ5%) although attenuated compared with controls (1.0 ± 0.2 l/min, Δ18%). Therefore, the rise in CO in the HTx recipients was solely dependent on increased SV (5 ± 1 ml, Δ5%) in contrast with the controls who displayed significant increases in both HR (6 ± 2 beats/min, Δ11%) and SV (5 ± 2 ml, Δ7%). The transient increase in femoral blood volume entering the leg during the first 40 s of passive movement was attenuated in the HTx recipients (24 ± 8 ml) compared with controls (93 ± 7 ml), whereas peripheral vascular function (FMD) appeared similar between HTx recipients (8 ± 2%) and controls (6 ± 1%). These data reveal that the absence of an HR increase in HTx recipients significantly impacts the peripheral vascular response to passive movement in this population and supports the concept that an increase in CO is a major contributor to exercise-induced hyperemia.

Limb-specific differences in flow-mediated dilation: the role of shear rate.

We sought to examine flow-mediated vasodilation (FMD) in both the arm [brachial artery (BA)] and lower leg [popliteal artery (PA)] of 12 young, healthy subjects. Vessel diameter, blood velocity, and calculated shear rate were determined with ultrasound Doppler following a suprasystolic cuff occlusion (5 min) in both the BA and PA and an additional reduced occlusion period (30-120 s) in the BA to more closely equate the shear stimulus observed in the PA. The BA revealed a smaller diameter and larger postischemic cumulative blood velocity [area under curve (AUC)] than the PA, a combination that resulted in an elevated postcuff cumulative shear rate (AUC) in the BA (BA: 25,419 +/- 2,896 s(-1).s, PA 8,089 +/- 1,048 s(-1).s; P < 0.05). Thus, when expressed in traditional terms, there was a tendency for the BA to have a greater FMD than the PA (6.5 +/- 1.0 and 4.5 +/- 0.8%, respectively; P = 0.1). However, when shear rate was experimentally matched (PA: 4.5 +/- 0.8%; BA: -0.4 +/- 0.4%) or mathematically normalized (PA: 6.8 x 10(-4) +/- 1.6 x 10(-4)%Delta/s(-1).s; BA: 2.5 x 10(-4) +/- 0.4 x 10(-4)%Delta/s(-1).s), the PA revealed a greater FMD per unit of shear rate than the BA (P < 0.05). These data highlight the importance of assessing the shear stimulus to which each vessel is exposed and reveal limb-specific differences in flow-mediated dilation.