Vascular Function and the Role of Oxidative Stress in Heart Failure, Heart Transplant, and Beyond

Witman, Melissa A. H.; Fjeldstad, Anette S.; McDaniel, John; Ives, Stephen J.; Zhao, Jia; Barrett-O’Keefe, Zachary; Nativi, J.N.; Stehlik, Josef; Wray, D. Walter; Richardson, Russell S.

doi:10.1161/hypertensionaha.112.193318

Cited by 32 publications

(47 citation statements)

References 64 publications

(68 reference statements)

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“…Our group has recently demonstrated that patients with HFrEF have reduced FMD, but not post occlusion RH, compared with healthy age-matched controls. 7 These data suggest that, in contrast to our current findings in HFpEF, conduit artery impairments alone contribute to the vascular dysfunction in HFrEF. This discrepancy between disease-related changes in the conduit and microvascular segments of the peripheral circulation may partially explain why many of the therapeutic approaches that have proven so successful in patients with HFrEF are somewhat less efficacious in the patient group with HFpEF.…”

Section: The Distinct Vascular Pathology Of Hfpefcontrasting

confidence: 96%

“…Although vascular dysfunction, assessed by FMD, has been well documented in patients with HFrEF, [4][5][6][7] and is an independent risk factor for an increased risk of clinical events and poor prognosis in this cohort, 4 much less is known about vascular function in the HFpEF population. In the current study, we observed a reduction in brachial artery FMD in patients with HFpEF compared with controls (figure 1), which initially seemed to indicate impaired conduit vascular function in this patient group.…”

Section: Conduit Vessel Vascular Function In Hfpefmentioning

confidence: 87%

“…[4][5][6][7] In contrast, very few studies have sought to evaluate vascular function in patients with HFpEF, and in the studies that have been undertaken, the results are equivocal. Using a MRI approach, Hundley et al 8 reported that flowmediated dilation (FMD) of the superficial femoral artery was similar between patients with HFpEF and age-matched controls.…”

Section: Introductionmentioning

confidence: 99%

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Evidence of microvascular dysfunction in heart failure with preserved ejection fraction

Lee

Barrett-O’Keefe

Garten

et al. 2015

Heart

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104

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Objective While vascular dysfunction is well-defined in HF patients with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of HF patients with preserved ejection fraction (HFpEF) are not well characterized. Thus, we sought test the hypothesis that HFpEF patients would demonstrate reduced vascular function, at both the conduit artery and microvascular levels, compared to controls. Methods We examined both conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperemia (RH) following 5 min of ischemia in 24 Class II–IV HFpEF patients and 24 healthy controls matched for age, sex, and brachial artery diameter. Results FMD was reduced in HFpEF patients compared to controls (HFpEF: 3.1 ± 0.7%; Controls: 5.1 ± 0.5%; P = 0.03). However, shear rate at time of peak brachial artery dilation was lower in HFpEF patients compared to controls (HFpEF: 42,070 ± 4,018 s−1; Controls: 69,018 ± 9,509 s−1; P = 0.01), and when brachial artery FMD was normalized for the shear stimulus, cumulative area-under-the-curve (AUC) at peak dilation, the between-group differences were eliminated (HFpEF: 0.11 ± 0.03 %/AUC; Controls: 0.09 ± 0.01 %/AUC; P = 0.58). RH, assessed as AUC, was lower in HFpEF patients (HFpEF: 454 ± 35 mL; Controls: 660 ± 63 mL; P < 0.01). Conclusions Collectively, these data suggest that maladaptations at the microvascular level contribute to the pathophysiology of HFpEF, while conduit artery vascular function is not diminished beyond that which occurs with healthy aging.

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Section: The Distinct Vascular Pathology Of Hfpefcontrasting

confidence: 96%

Section: Conduit Vessel Vascular Function In Hfpefmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

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Evidence of microvascular dysfunction in heart failure with preserved ejection fraction

Lee

Barrett-O’Keefe

Garten

et al. 2015

Heart

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104

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“…However, it should be noted that the single PLM model, which greatly reduces the stimulation of the group III mechanoreceptors as evidenced by the lack of a HR response in either subject group, also revealed that the FBF response in the HFrEF was still greatly attenuated. In combination, these data are consistent with the fact that impaired endothelium-dependent vasodilation has long been associated with many cardiovascular diseases, including HF [30, 31], but extends these findings to movement-induced hyperemia, uncomplicated by changes in metabolism. Utilization of the single PLM removed the influence of the persistent mechanical stimulus associated with continuous movement of the leg.…”

Section: Discussionsupporting

confidence: 84%

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

Witman

Ives

Trinity

et al. 2015

International Journal of Cardiology

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BACKGROUND The complex pathophysiology of heart failure (HF) creates a challenging paradigm to differentiate the role of central and peripheral hemodynamic dysfunction during conventional exercise. Adopting a novel reductionist approach with potential clinical relevance, we studied the central and peripheral contributors to both continuous and single passive leg movement (PLM)–induced hyperemia in 14 HF patients with reduced ejection fraction (HFrEF) and 13 controls. METHODS Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), and femoral artery blood flow (FBF) were recorded during PLM. RESULTS The FBF response (area under the curve; AUC) to 60 seconds of continuous PLM was attenuated in the HFrEF (25 ± 15 ml AUC) compared to controls (199 ± 34 ml AUC) as were peak changes from baseline for FBF, leg vascular conductance (LVC), CO, and HR. During single PLM, increases in CO and HR were smaller and no longer different between groups, supporting the use of this modality to assess groups with disparate central hemodynamics. Interestingly, single PLM-induced hyperemia, likely predominantly driven by flow-mediated vasodilation due to minimal vessel deformation, was essentially nonexistent in the HFrEF (−9 ± 10 ml AUC) in contrast to the controls (43 ± 25 ml AUC). CONCLUSIONS These data fail to support a HFrEF-associated exaggeration in the mechanoreceptor driven component of the exercise pressor response. In fact, by exhibiting limited central hemodynamic responses compared to the controls, the observed attenuation in movement-induced FBF in HFrEF appears largely due to peripheral vascular dysfunction, particularly flow-mediated vasodilation.

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“…Previously it has been documented that an acute antioxidant cocktail (AOC) of known efficacy 33, 34 is capable of improving vascular function, as assessed by FMD, in the elderly population 33 and heart transplant recipients with history of heart failure 35 , populations with increased CVD risk and a definitive incident, respectively. The AOC-induced improvement in redox balance 36 likely attenuates free radical mediated reductions in nitric oxide bioavailability, thus increasing endothelial dependent flow mediated dilation 33–35 .…”

Section: Introductionmentioning

confidence: 99%

Vascular Dysfunction and Chronic Obstructive Pulmonary Disease

et al. 2014

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Chronic obstructive pulmonary disease is characterized by low pulmonary function, inflammation, free-radical production, vascular dysfunction and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with chronic obstructive pulmonary disease (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double blind, randomized, placebo controlled, crossover design, patients with chronic obstructive pulmonary disease and controls ingested placebo or the antioxidant cocktail (Vitamin-C, Vitamin-E, α-lipoic acid) after which brachial artery flow mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (Vitamin-C and superoxide dismutase activity) and higher levels of oxidative stress (Thiobarbituic acid reactive species) in comparison to controls. The patients also displayed lower basal flow mediated dilation (p<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 vs. 4.7±0.6 %, p<0.05, placebo vs. antioxidant cocktail), but not controls (6.7±0.6 vs. 6.9±0.7 %, p>0.05, placebo vs. antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in the patients (14±1 vs. 11±1 m·s−1, p<0.05, placebo vs. antioxidant cocktail), while not affecting controls (11±2 vs. 10±1 m·s−1, p>0.05, placebo vs. antioxidant). Patients with chronic obstructive pulmonary disease exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically-mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.

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Vascular Function and the Role of Oxidative Stress in Heart Failure, Heart Transplant, and Beyond

Cited by 32 publications

References 64 publications

Evidence of microvascular dysfunction in heart failure with preserved ejection fraction

Evidence of microvascular dysfunction in heart failure with preserved ejection fraction

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

Vascular Dysfunction and Chronic Obstructive Pulmonary Disease

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