Health Canada advisory impacts on the prevalence of oral codeine use in the Pediatric Canadian population: comparative study across provinces.

Health Canada (HC) has, since 2013, issued safety alerts restricting the use of codeine-containing drugs among breastfeeding women and children/adolescents under 18 years of age. These products are linked to breathing problems among ultra-rapid CYP2D6 metabolizers and early use of opioid can lead to future opioid misuse. Using a multi-province population-based cohort study, we estimate the impact of federal safety alerts on annual rates of codeine use in the Canadian pediatric population. We analyzed data from 8,156,948 children/adolescents in five Canadian provinces between 1996 and 2021, using a common protocol. Children/adolescents were categorized as: ≤ 12 years (children) or > 12 years (adolescents). We defined codeine exposure by ≥ 1 prescription filled for codeine alone or combined with other medications. For both age categories, we obtained province-specific codeine prescription filling rates per calendar year by dividing the number of children/adolescents with ≥ 1 codeine prescription filled by the number of person-time. Annual rates of codeine use per 1000 persons vary by province from 3.0 (Quebec) to 10.1 (Manitoba) in children, and from 5.5 to 51.3 in adolescents. After the 2013 HC advisory, exposure decreased in all provinces (adjusted level change from - 0.6 to - 18.4%) in children and from - 2.1 to - 17.9% in adolescents after the 2016 advisory. Annual rates declined over time in all provinces, following HC safety alerts specific to each of the two age categories.

Coronary Artery Tortuosity and Spontaneous Coronary Artery Dissection: Association With Echocardiography and Global Longitudinal Strain, Fibromuscular Dysplasia, and Outcomes.

BACKGROUND: The etiology and significance of coronary artery tortuosity (TCA) among patients with spontaneous coronary artery dissection (SCAD) are unknown. The aim of this prospective imaging cohort study was to report echocardiographic findings and evaluate whether TCA correlates with cardiac anatomy and function among patients with SCAD. Comorbidities including fibromuscular dysplasia (FMD) and outcomes were also assessed. METHODS: TCA was determined on coronary angiography performed during the diagnosis of SCAD, and cardiac structure and function were evaluated using prospective comprehensive echocardiography. RESULTS: Among 116 patients with SCAD, the mean age at echocardiography was 50.8 ± 8.8 years, a median of 10.9 months after SCAD. Sixty-two patients (53.4%) had FMD, 41 (35.3%) had histories of hypertension, and 17 (14.8%) were hypertensive during echocardiography. Most patients (n = 78 [69%]) had normal left ventricular geometry with normal median ejection fraction (61%; interquartile range, 56% to 64%) and normal global longitudinal strain (-22.2%; interquartile range, -24.0% to -19.9%). Fifteen patients (13.4%) had diastolic dysfunction that was associated with hypertension at the time of echocardiography. Patients with TCA (n = 96 [82.8%]) were older (mean age, 52.1 ± 8.0 vs 44.7 ± 9.9 years; P < .001) with a higher prevalence of FMD (59.4% vs 25%, P = .007) but a similar prevalence of hypertension (35% vs 35%, P > .99) compared with patients without TCA. Across the age range (31.5 to 66.9 years), each decade of age was associated with an approximately 0.89-unit increase in coronary tortuosity score (P < .0001). Echocardiographic parameters were not significantly different between the two groups. Median follow-up duration was 4.4 years (95% CI, 3.8 to 5.2 years). The Kaplan-Meier 3-year SCAD recurrence rate was 9.4% (95% CI, 3.7% to 14.8%). There were no deaths. CONCLUSIONS: The majority of patients with SCAD had normal or near normal echocardiographic results, including global longitudinal strain, with no differences according to TCA. However, patients with SCAD with TCA were older, with a higher prevalence of FMD.

Metastatic Melanoma Invading the Minor Duodenal Papilla in a Patient With Pancreas Divisum Causing Acute Recurrent Pancreatitis: A Case Report.

Metastasis to the gastrointestinal (GI) tract should always be a consideration when melanoma, particularly metastatic disease, is diagnosed. While metastasis to the small intestine is common, given its rich blood supply, metastasis to the pancreatic ducts is extremely rare. In patients with pancreatic divisum, disease spread to the minor papilla can greatly increase the chance of developing pancreatitis due to the potential for increased pancreatic intraductal pressure. We present one unique case of metastatic melanoma to the minor duodenal papilla causing pancreatitis.

Unusual Instance of Primary Diffuse Large B-cell Lymphoma of the Colon.

Diffuse large B-cell lymphoma (DLBCL) commonly affects the gastrointestinal (GI) tract, although primary DLBCL rarely occurs in the colon. Primary colorectal lymphoma is a surprisingly rare diagnosis, accounting for a minute percentage of GI lymphomas and colorectal malignancies. We present an interesting case of an immunocompromised young adult female who was diagnosed with DLBCL confined to a cecum polyp after she underwent a colonoscopy for a GI bleed. The lymphoma presented endoscopically as a semi-sessile polyp in the cecum that was successfully removed. The patient was treated with appropriate therapy of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

Massive Lower Gastrointestinal Hemorrhage as a Complication of Severe Campylobacter Enteritis.

Campylobacter enteritis is typically caused by Campylobacter jejuni or Campylobacter coli and is a major cause of diarrheal illness worldwide. Patients with Campylobacter gastroenteritis can be asymptomatic, but commonly present with a wide range of clinical symptoms including abdominal pain, diarrhea, vomiting, and occasionally self-resolving hematochezia. Although hematochezia can occur, acute massive lower gastrointestinal (GI) bleeding is a rare complication of Campylobacter gastroenteritis and should be considered as a possible differential diagnosis in the presentation of lower GI bleeds. We describe a unique case of a 48-year-old male who presented with massive lower GI bleeding requiring multiple transfusions and admission to the medical intensive unit; the patient was ultimately diagnosed with severe Campylobacter gastroenteritis.

Locomotor Muscle Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction.

[Figure: see text].

A Primary Care Approach to Constipation in Adults with Intellectual and Developmental Disabilities.

Constipation is a condition that is very prevalent and is reported in up to 40 percent of individuals with intellectual and developmental disabilities (IDD). Constipation in this patient population is most commonly secondary to neuromuscular abnormalities, immobility, suboptimal diet, and medication side effects. History taking is frequently limited in adults with IDD due to communication barriers, often leading to a missed diagnosis of constipation. Inadequately treated constipation may lead to adverse effects including behavioral disturbances, fecal impaction, intestinal obstruction, and even death from intestinal perforation and sepsis. As a result, a high index of suspicion must exist for this patient population. Treatment in these patients requires an individualized approach, to reduce the constipation and its associated health complications.

A Prolonged Neurological Presentation of Legionnaire's Disease.

Legionnaire's disease is an uncommon pneumonic disease that can carry a mortality rate up to 20%. It commonly presents as an atypical lower respiratory illness. However, it is important to be mindful of the various extra-pulmonic presentations of the infection. Here, we present a case of a 51-year-old female who presented to the emergency department with lethargy, slurred speech, and confusion. Legionella has been reported to present with neurological symptoms but it is not a common occurrence in each hospitalization. These neurological symptoms often lead to an extensive workup and the complexity of the diagnostic workup can significantly influence patient outcome. However, it is crucial that physicians follow a systemic approach to establish a diagnosis in an expedited manner. This case emphasizes the importance of key objective evidence of legionella that can help guide a physician's diagnostic approach.

Kaolin Clay Anemia.

Iron deficiency anemia is a common diagnosis encountered in the nutrition, primary care, and gastroenterology fields. Iron deficiency anemia most often leads to evaluation for various malabsorption disorders and colonoscopy to exclude colon cancer as an etiology. We present a case of iron deficiency anemia that was caused by geophagia. After the culprit dietary habit was stopped, the patient's iron deficiency anemia subsequently resolved.

The Significance of "Contractile Reserve" in the Echocardiographic Assessment of Athletic Heart Syndrome.

The clinical distinction between athlete's heart and structural heart disease in the echocardiography laboratory is often challenging. We present a case where athletic heart syndrome was promptly differentiated from pathology with a simple maneuver during echocardiography.

α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction.

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (-15 ± 7%) compared with controls (-36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (-12 ± 4, -10 ± 4, and -9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (-8 ± 5, -10 ± 3, and -14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

Incidence and variables associated with short and long-term mortality in patients with systemic lupus erythematosus and sepsis admitted in intensive care units.

Background Infections are common among patients with systemic lupus erythematosus (SLE), and are associated with increased morbidity and mortality. Objectives To determine whether SLE is an independent risk factor for short- and long-term mortality in patients admitted to an intensive care unit (ICU) with sepsis, and to identify the characteristics of SLE patients admitted to an ICU with sepsis. Methods A retrospective age- and sex-matched cohort study, based on data of the SEPSIS-ISR (Sepsis Israel) Registry, an ongoing study that collects data on all patients admitted with sepsis to the ICUs. The primary outcome was to determine whether SLE is an independent risk factor for 30-day and 3-year mortality. Secondary outcomes were 30-day and 3-year survival rates, and the identification of variables associated with mortality within the group of patients with SLE. Results In total, 29 SLE and 87 non-SLE patients (median age 55 years; 79.3% females) were included. The primary sites of infection as well as pathogen distributions were similar between the two groups. The most common infections among the SLE and non-SLE patients were pneumonia (48.3 vs. 31%, p = 0.09), urinary tract infection (20.7 vs. 14.9%, p = 0.56) and peritonitis (13.8 vs. 16.1%, p = 0.77). Severe sepsis and septic shock were diagnosed in 79.3 versus 80.5% ( p = 0.89) and 55.2 versus 33.3% ( p = 0.04) of the SLE and non-SLE patients, respectively. The 30-day and 3-year survival rates did not differ between SLE and non-SLE patients, and were 69 versus 67.8% ( p = 0.79) and 41.4 versus 47.1% ( p = 0.69), respectively. In multivariate Cox regression analysis, age (hazard ratio (HR) = 1.02; 95% confidence interval (CI) 1.00-1.05) and cardiovascular involvement during sepsis (HR = 3.32; 95% CI 1.4-7.86) were significant independent risk factors for 30-day mortality. Multiorgan dysfunction during sepsis admission was associated with increased 3-year mortality (HR = 1.37; 95% CI 1.07-1.75). Conclusions SLE is not an independent risk factor for 30-day or 3-year mortality following ICU admission with sepsis. Increased late mortality was associated with congestive heart failure within the SLE patients alone. None of the SLE-related variables were statistically different between the living and deceased SLE patients.

Metaboreceptor activation in heart failure with reduced ejection fraction: Linking cardiac and peripheral vascular haemodynamics.

NEW FINDINGS: What is the central question of this research? Do patients with heart failure with reduced ejection fraction (HFrEF) exhibit a greater dependence on cardiac or peripheral vascular haemodynamics across multiple levels of muscle metaboreflex activation provoked by postexercise circulatory occlusion? What is the main finding and its importance? The metaboreflex-induced pressor response in HFrEF patients is governed almost entirely by the peripheral circulation, which places a substantial haemodynamic load on the failing heart. This maladaptive response exacerbates the disease-related impairment of systolic function that is a hallmark feature of HFrEF and may therefore contribute to exercise intolerance in this patient group. ABSTRACT: We sought to evaluate the muscle metaboreflex in heart failure with reduced ejection fraction (HFrEF) patients, with an emphasis on the interaction between cardiac and peripheral vascular haemodynamics across multiple levels of metaboreceptor activation. In 23 HFrEF patients (63 ± 2 years of age) and 15 healthy control subjects (64 ± 3 years of age), we examined changes in mean arterial pressure, cardiac output, systemic vascular conductance, effective arterial elastance, stroke work and forearm deoxyhaemoglobin concentration during metaboreceptor activation elicited by postexercise circulatory occlusion (PECO) after three levels of static-intermittent handgrip exercise (15, 30 and 45% maximal voluntary contraction). Across workloads, the metaboreflex-induced increase in deoxyhaemoglobin and mean arterial pressure were similar between groups. However, in control subjects, the pressor response was driven by changes (Δ) in cardiac output  (Δ495 ± 155, Δ564 ± 156 and Δ666 ± 217 ml min-1 ), whereas this change was accomplished by intensity-dependent reductions in systemic vascular conductance in patients with HFrEF (Δ-4.9 ± 1.5, Δ-9.1 ± 1.9 and Δ-12.7 ± 1.8 ml min mmHg-1 ). This differential response contributed to the exaggerated increases in effective arterial elastance in HFrEF patients compared with control subjects, coupled with a blunted response in stroke work in the HFrEF patients. Together, these findings indicate a preserved role of the metaboreflex-induced pressor response in HFrEF but suggest that this response is governed by changes in the peripheral circulation. The net effect of this response appears to be maladaptive, as it places a substantial haemodynamic load on the left ventricle that may exacerbate left ventricular systolic dysfunction and contribute to exercise intolerance in this patient population.

Impaired skeletal muscle vasodilation during exercise in heart failure with preserved ejection fraction.

BACKGROUND: Exercise intolerance is a hallmark symptom of heart failure patients with preserved ejection fraction (HFpEF), which may be related to an impaired ability to appropriately increase blood flow to the exercising muscle. METHODS: We evaluated leg blood flow (LBF, ultrasound Doppler), heart rate (HR), stroke volume (SV), cardiac output (CO), and mean arterial blood pressure (MAP, photoplethysmography) during dynamic, single leg knee-extensor (KE) exercise in HFpEF patients (n=21; 68 ± 2 yrs) and healthy controls (n=20; 71 ± 2 yrs). RESULTS: HFpEF patients exhibited a marked attrition during KE exercise, with only 60% able to complete the exercise protocol. In participants who completed all exercise intensities (0-5-10-15 W; HFpEF, n=13; Controls, n=16), LBF was not different at 0 W and 5 W, but was 15-25% lower in HFpEF compared to controls at 10 W and 15 W (P<0.001). Likewise, leg vascular conductance (LVC), an index of vasodilation, was not different at 0 W and 5 W, but was 15-20% lower in HFpEF compared to controls at 10 W and 15 W (P<0.05). In contrast to these peripheral deficits, exercise-induced changes in central variables (HR, SV, CO), as well as MAP, were similar between groups. CONCLUSIONS: These data reveal a marked reduction in LBF and LVC in HFpEF patients during exercise that cannot be attributed to a disease-related alteration in central hemodynamics, suggesting that impaired vasodilation in the exercising skeletal muscle vasculature may play a key role in the exercise intolerance associated with this patient population.

Nitric oxide-mediated vascular function in sepsis using passive leg movement as a novel assessment: a cross-sectional study.

Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.

Is the Current BST ePortfolio fulfilling its Role in the Training of Clinical Medicine SHOs?

While the objective recording of clinical competencies in an electronic portfolio (ePortfolio) has become a key aspect of basic specialist training (BST), it continues to divide opinion. We surveyed medical trainees and their supervisors in the Dublin region examining their views of the ePortfolio and workplace-based assessments (WPBAs). Responses were received from 27 of 149 (18.1%) SHOs and 24 of 307 (7.9%) consultants. Our results highlight significant dissatisfaction amongst trainees with 20 (74.1%) stating that the ePortfolio is not an effective educational tool. Consultants had more mixed views. While 16 (66.7%) reported that feedback sessions were useful for trainee development, only 4 (16.7%) found the ePortfolio to be useful in highlighting trainees' strengths and weaknesses. Although other studies have emphasised its educational potential, our results suggest that practical barriers, such as time constraints and a lack of training, lead to poor engagement and a negative view of the ePortfolio.

Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism.

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.

Evidence of microvascular dysfunction in heart failure with preserved ejection fraction.

OBJECTIVE: While vascular dysfunction is well defined in patients with heart failure (HF) with reduced ejection fraction (HFrEF), disease-related alterations in the peripheral vasculature of patients with HF with preserved ejection fraction (HFpEF) are not well characterised. Thus, we sought to test the hypothesis that patients with HFpEF would demonstrate reduced vascular function, at the conduit artery and microvascular levels, compared with controls. METHODS: We examined conduit artery function via brachial artery flow-mediated dilation (FMD) and microvascular function via reactive hyperaemia (RH) following 5 min of ischaemia in 24 patients with Class II-IV HFpEF and 24 healthy controls matched for age, sex and brachial artery diameter. RESULTS: FMD was reduced in patients with HFpEF compared with 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 patients with HFpEF compared with controls (HFpEF: 42 070±4018/s; CONTROLS: 69 018±9509/s, p=0.01), and when brachial artery FMD was normalised 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 patients with HFpEF (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.

Endogenous endothelin-1 and femoral artery shear rate: impact of age and implications for atherosclerosis.

BACKGROUND: Both altered shear rate and endothelin-1 (ET-1) are associated with the age-related development of atherosclerosis. However, the role of ET-1, a potent endogenous vasoconstrictor, in altering shear rate in humans, especially in the atherosclerotic-prone vasculature of the leg, is unknown. Therefore, this study examined the contribution of ET-1 to the age-related alterations in common femoral artery (CFA) shear rate. METHOD: BQ-123, a specific endothelin type A (ET(A)) receptor antagonist, was infused into the CFA, and diameter and blood velocity were measured by Doppler ultrasound in young (n = 8, 24 ±â€Š2 years) and old (n = 9, 70 ±â€Š2 years) study participants. RESULTS AND CONCLUSION: The old had greater intima-media thickening in the CFA, indicative of a preatherogenic phenotype. Prior to infusion, the old study participants exhibited reduced mean shear rate (27 ±â€Š3/s) compared with the young study participants (62 ±â€Š9/s). This difference was likely driven by attenuated antegrade shear rate in the old as retrograde shear rate was similar in the young and old. Inhibition of ETA receptors, by BQ-123, increased leg blood flow in the old, but not in the young, abolishing age-related differences. Older study participants had a larger CFA (young: 0.82 ±â€Š0.03 cm, old: 0.99 ±â€Š0.03 cm) in which BQ-123 induced significant vasodilation (5.1 ±â€Š1.0%), but had no such effect in the young (-0.8 ±â€Š0.8%). Interestingly, despite the age-specific, BQ-123-induced increase in leg blood flow and CFA diameter, shear rate patterns remained largely unchanged. Therefore, ET-1, acting through the ETA receptors, exerts a powerful age-specific vasoconstriction. However, removal of this vasoconstrictor stimulus does not augment mean shear rate in the old.

Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.