A differing role of oxidative stress in the regulation of central and peripheral hemodynamics during exercise in heart failure

Abstract

This study sought to characterize the role of free radicals in regulating central and peripheral hemodynamics at rest and during exercise in patients with heart failure (HF). We examined cardiovascular responses to dynamic handgrip exercise (4, 8, and 12 kg at 1 Hz) following consumption of either a placebo or acute oral antioxidant cocktail (AOC) consisting of vitamin C, E, and α-lipoic acid in a balanced, crossover design. Central and peripheral hemodynamics, mean arterial pressure, cardiac index, systemic vascular resistance (SVR), brachial artery blood flow, and peripheral (arm) vascular resistance (PVR) were determined in 10 HF patients and 10 age-matched controls. Blood assays evaluated markers of oxidative stress and efficacy of the AOC. When compared with controls, patients with HF exhibited greater oxidative stress, measured by malondialdehyde (+36%), and evidence of endogenous antioxidant compensation, measured by greater superoxide dismutase activity (+83%). The AOC increased plasma ascorbate (+50%) in both the HF patients and controls, but significant systemic hemodynamic effects were only evident in the patients with HF, both at rest and throughout exercise. Specifically, the AOC reduced mean arterial pressure (-5%) and SVR (-12%) and increased cardiac index (+7%) at each workload. In contrast, peripherally, brachial artery blood flow and PVR (arm) were unchanged by the AOC. In conclusion, these data imply that SVR in patients with HF is, at least in part, mediated by oxidative stress. However, this finding does not appear to be the direct result of muscle-specific changes in PVR.

Heart failure and movement-induced hemodynamics: Partitioning the impact of central and peripheral dysfunction

“…Considering that PLM specifically isolates the group III mechanoreceptors, thought to be sensitized in HF, the similar MAP response to the initiation of continuous PLM, was somewhat surprising. However, this finding actually further supports previous work by Middlekauf et al [25] and our own group [26] that was unable to reveal any evidence of an exaggerated exercise pressor reflex during passive arm exercise and active handgrip exercise, respectively, in patients with HFrEF. It is acknowledged that the lower baseline MAP and the lack of an exaggerated exercise pressor reflex could be attributed to the patient's pharmacological therapies, but this approach was chosen to minimize risk and study these patients with their disease pharmacologically controlled.…”

The Mechanoreflex and Hemodynamic Response to Passive Leg Movement in Heart Failure

“…During exercise, patients with HF often exhibit reduced muscle blood flow and convective O 2 transport (3,10,27,38), as well as exaggerated renal vasoconstriction (19), implicating exaggerated total peripheral resistance (TPR) as a contributor to the EPR in HF (39). Recent work performed by our group, revealed that during knee extensor exercise patients with HF exhibit reduced femoral blood flow (3), which following partial blockade of lower limb muscle afferents was somewhat restored to the level of controls.…”

Peripheral vascular function, oxygen delivery and utilization: the impact of oxidative stress in aging and heart failure with reduced ejection fraction

“…Following AO consumption, we documented a marked increase in circulating AO capacity, but the consequence of this intervention on vascular function was less clear, as administration of the AO did not alter the FMD or reactive hyperemia (RH, an index of microvascular function) responses compared with placebo in the HFrEF patients. This was followed up by a study employing HG exercise to more broadly examine the impact of oral AO consumption on arterial blood pressure and indices of both central (i.e., CO and systemic vascular resistance [SVR]) and peripheral (arm blood flow and vascular resistance) hemodynamics in HFrEF patients and age-matched controls [71]. Although AO ingestion significantly increased plasma ascorbate concentration and endogenous AO activity (catalase) in both the patients and controls, only in the patients with HF did this intervention result in a significant hemodynamic response.…”

“…However, this did not appear to be the result of limb or skeletal muscle-specific changes in PVR. Together, these studies [47, 71] have identified a somewhat varied response to AO consumption in HFrEF, which likely reflects the complex and heterogeneous manner in which oxidative stress may impact the circulatory system in this patient group. Whether this AO intervention could prove efficacious in rescuing the decrement in vascular function identified using the PLM model has not been examined, but is certainly a worthy of future investigation.…”