Publications by authors named "Carl J Ade"

We investigated second-messenger signalling components linked to the stimulation of G protein-coupled receptors (e.g. thromboxane A and bradykinin B2 receptors) on the sensory endings of thin fibre muscle afferents in the chronic mechanoreflex sensitization in rats with myocardial infarction-induced heart failure with reduced ejection fraction (HF-rEF).

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Background: 5-fluorouracil (5-FU) is the second most common cancer chemotherapy associated with short- and long-term cardiotoxicity. Although the mechanisms mediating these toxicities are not well understood, patients often present with symptoms suggestive of microvascular dysfunction. We tested the hypotheses that patients undergoing cancer treatment with 5-FU based chemotherapy regimens would present with impaired microvascular reactivity and that these findings would be substantiated by decrements in endothelial nitric oxide synthase (eNOS) gene expression in 5-FU treated human coronary artery endothelial cells (HCAEC).

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Article Synopsis
  • Cerebral small vessel disease (cSVD) is linked to ischemic stroke and dementia, and this systematic review aims to clarify its relationship with cerebrovascular reactivity (CVR), cerebral autoregulation, and arterial stiffness (AS).
  • The review analyzed 142 studies and conducted meta-analyses on 60 of them, revealing that CVR, cerebral autoregulation, and AS were significantly associated with cSVD in a majority of cases.
  • The findings indicate a borderline association between impaired CVR and cSVD, and a strong link between increased AS and cSVD, suggesting that further research into these vascular factors as potential risk contributors is necessary.
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Objective: Athletes are susceptible to acute respiratory tract infections, including SARS-CoV-2, which can affect cardiovascular function. We aimed to evaluate the impact of COVID-19 infection and quarantine on cardiac function in male and female collegiate athletes.

Methods: We conducted a single-center, prospective, case-control study and performed transthoracic echocardiography in a diverse group of convalescent SARS-CoV-2-positive athletes following a 10-14-day quarantine, matched to non-SARS-CoV-2 athletes.

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Solid tumors contain hypoxic regions that contribute to anticancer therapy resistance. Thus, mitigating tumor hypoxia may enhance the efficacy of radiation therapy which is commonly utilized for patients with prostate cancer. Increasing perfusion pressure in the prostate with head-up tilt (HUT) may augment prostate tumor perfusion and decrease hypoxia.

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In non-cancer populations, inorganic dietary nitrate (NO) supplementation is associated with enhanced cardiorespiratory function but remains untested in patients with a history of cancer. Therefore, this pilot study sought to determine if oral NO supplementation, as a supportive care strategy, increases left ventricular (LV) function and exercise performance in survivors of cancer treated with anticancer therapy while simultaneously evaluating the feasibility of the methods and procedures required for future large-scale randomized trials. Two cohorts of patients with a history of cancer treated with anticancer chemotherapy were recruited.

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This study sought to describe and relate the factors associated with complications and delays in adjuvant chemotherapy in patients with ovarian cancer treated with primary cytoreductive surgery. Serum from patients diagnosed with ovarian cancer scheduled for primary cytoreductive surgery were analyzed for prealbumin, 25-OH Vitamin D, intracellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), monocyte chemoattractant protein 2 (MCP-2), macrophage derived chemokine (MDC). Postoperative complications were identified using common terminology criteria for adverse events 4.

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Cardiovascular diseases (CVD) are the leading cause of death worldwide and the risk of developing CVD is markedly increased following anthracycline chemotherapy treatment. Anthracyclines are an essential component of the cancer treatment regimen used for common forms of cancer in male and female children, adolescents, young adults, and older adults. Increased CVD risk with anthracyclines occurs, in part, due to vascular dysfunction-impaired endothelial function and arterial stiffening.

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Introduction: Since the COVID-19 pandemic there is concern for subclinical cardiac pathology in the absence of clinical symptoms in collegiate athletes, we present 4 cases of abnormal left ventricular global longitudinal strain (LVGLS), a "red-flag" for potential COVID-19 myocardial disease, following diagnosis with diverse abnormalities reported via multimodality imaging weeks into recovery.

Methods: Cardiac imaging studies consisting of transthoracic echocardiography (TTE) and cardiovascular magnetic resonance imaging (CMR) were performed 10 days post-COVID-19 diagnosis and several weeks into recovery.

Results: Initial TTE revealed abnormal left ventricular global longitudinal strain (LVGLS), an identified "red-flag" for potential COVID-19 myocardial disease.

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Article Synopsis
  • Mechanical and metabolic signals from skeletal muscle contractions activate sensory fibers that lead to increased sympathetic nerve activity (SNA) and blood pressure during exercise, known as the exercise pressor reflex (EPR).
  • Heart failure with reduced ejection fraction (HF-rEF) causes exaggerated SNA responses, resulting in exercise intolerance in affected individuals.
  • In a study with HF-rEF rats, the ASIC1a antagonist reduced SNA responses during muscle contractions, suggesting that ASIC1a plays a novel role in mechanosensory activation related to the EPR in heart failure, which differs from its role in healthy animals.
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Pulmonary hypertension (PH) has previously been characterized as a disease of the pulmonary vasculature that subsequently results in myocardial dysfunction. Heart failure compromises skeletal muscle microvascular function, which contributes to exercise intolerance. Therefore, we tested the hypothesis that such changes might be present in PH.

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In heart failure with reduced ejection fraction (HFrEF), nitric oxide-soluble guanylyl cyclase (sGC) pathway dysfunction impairs skeletal muscle arteriolar vasodilation and thus capillary hemodynamics, contributing to impaired oxygen uptake (V̇O) kinetics. Targeting this pathway with sGC activators offers a new treatment approach to HFrEF. We tested the hypotheses that sGC activator administration would increase the O delivery (Q̇O)-to-V̇O ratio in the skeletal muscle interstitial space (POis) of HFrEF rats during twitch contractions due, in part, to increases in red blood cell (RBC) flux (f), velocity (V), and capillary hematocrit (Hct).

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Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fiber muscle afferents and produce reflex increases in sympathetic nerve activity and blood pressure during exercise (i.e., the exercise pressor reflex; EPR).

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New Findings: What is the central question of this study? Does impairment in the dynamics of O transport in skeletal muscle during a series of contractions constitute a potential mechanism underlying reduced exercise capacity in pulmonary hypertension? What is the main finding and its importance? Pulmonary hypertension compromises the dynamic matching of skeletal muscle O delivery-to-utilization following contraction onset in the rat spinotrapezius muscle. These results implicate a role for vascular dysfunction in the slow kinetics and exercise intolerance present in pulmonary hypertension.

Abstract: Pulmonary hypertension (PH) is characterized by pulmonary vascular dysfunction and exercise intolerance due, in part, to compromised pulmonary and cardiac function.

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Introduction: Concerns have been raised that COVID-19 face coverings compromise lung function and pulmonary gas exchange to the extent that they produce arterial hypoxemia and hypercapnia during high intensity exercise resulting in exercise intolerance in recreational exercisers. This study therefore aimed to investigate the effects of a surgical, flannel or vertical-fold N95 masks on cardiorespiratory responses to incremental exercise.

Methods: This investigation studied 11 adult males and females at rest and while performing progressive cycle exercise to exhaustion.

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We tested the hypothesis that limb vascular conductance (LVC) would increase during the immediate recovery phase of dynamic exercise above, but not below, critical power (CP) indicating a threshold for muscular contraction-induced impedance of limb blood flow (LBF). CP (115 ± 26 W) was determined in 7 men and 7 women who subsequently performed ∼5 min of near-supine cycling exercise both below and above CP. LVC demonstrated a greater increase during immediate recovery and remained significantly higher following exercise above, compared to below, CP (all p < 0.

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Background: Cancer survivors are at greater risk for cardiovascular disease (CVD) than second malignancy, resulting in a decreased quality of life and increased cost of care. Additional knowledge of CVD prevention by identifying possible risk factors has clinical relevance. Our main objective was to determine the relevance of a clinical index of arterial stiffness, pulse pressure, in predicting CVD mortality in cancer patients, with a second objective to examine its relationship with cancer mortality.

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Purpose: Cancer patients with a history of radiotherapy are at an increased risk of ischemic heart disease. Preclinical animal studies demonstrate markedly impaired acetylcholine (ACh)-mediated endothelium-dependent vasorelaxation within days to weeks post-irradiation, however, whether microvascular function is affected in the intact human circulation during cancer radiation therapy has yet to be determined.

Materials And Methods: Using laser-Doppler flowmetry, microvascular endothelium-dependent and independent responses were evaluated through iontophoresis of acetylcholine (ACh) (part 1, n = 7) and sodium nitroprusside (SNP) (part 2, n = 8), respectively, in women currently receiving unilateral chest adjuvant radiation therapy for breast cancer.

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The primary purpose of this investigation was to determine the role played by endoperoxide 4 receptors (EP4-R) and thromboxane A receptors (TxA-R) during isolated dynamic muscle mechanoreflex activation in rats with heart failure with reduced ejection fraction (HF-rEF) and sham-operated healthy controls. We found that injection of the EP4-R antagonist L-161,982 (1 μg) into the arterial supply of the hindlimb had no effect on the peak pressor response to dynamic hindlimb muscle stretch in HF-rEF (n = 6, peak ∆MAP pre: 27 ± 7; post: 27 ± 4 mm Hg; P = 0.99) or sham (n = 6, peak ∆MAP pre: 15 ± 3; post: 13 ± 3 mm Hg; P = 0.

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Background: Recent evidence suggests prostate cancer independent of treatment has atrophic effects on whole heart and left ventricular (LV) masses, associated with reduced endurance exercise capacity. In a pre-clinical model, we tested the hypothesis that high-intensity training could prevent cardiac atrophy with prostate cancer and alter cardiac protein degradation mechanisms.

Methods: Dunning R-3327 AT-1 prostate cancer cells (1×10) were injected into the ventral prostate lobe of 5-6 mo immunocompetent Copenhagen rats (n=24).

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We investigated the effects of chronic (∼7 weeks) treatment with the angiotensin converting enzyme (ACE) inhibitor Captopril in rats with heart failure with reduced ejection fraction (HF-rEF) on brain blood flow (BF; radiolabeled microspheres) at rest and during submaximal exercise. We hypothesized that middle cerebral, posterior cerebral, and cerebellar BF during submaximal exercise (20 m/min, 5% incline) would be reduced in rats with HF-rEF (n = 10) compared to healthy (SHAM, n = 10) controls and HF-rEF rats chronically treated with Captopril (HF-rEF + Cap., n = 20).

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Purpose: The purpose of the study was to investigate the prevalence of poor health behaviors (low dietary quality, low physical activity (PA), and high body mass index (BMI)) in cancer patients and the general population and its relationship with receipt of patient-physician recommendations.

Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2005-2014 to compare 1846 patients with a history of cancer to 16,641 with no cancer history. BMI was measured during physical exam.

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New Findings: What is the central question of this study? Do endoperoxide 4 and thromboxane A receptors, which are receptors for cyclooxygenase products of arachidonic metabolism, on thin fibre muscle afferents play a role in the chronic mechanoreflex sensitization present in rats with heart failure with reduced ejection fraction (HF-rEF)? What is the main finding and its importance? The data do not support a role for endoperoxide 4 receptors or thromboxane A receptors in the chronic mechanoreflex sensitization in HF-rEF rats.

Abstract: We investigated the role of cyclooxygenase metabolite-associated endoperoxide 4 receptors (EP4-R) and thromboxane A receptors (TxA -R) on thin fibre muscle afferents in the chronic mechanoreflex sensitization in rats with myocardial infarction-induced heart failure with reduced ejection fraction (HF-rEF). We hypothesized that injection of either the EP4-R antagonist L-161,982 (1 µg) or the TxA -R antagonist daltroban (80 µg) into the arterial supply of the hindlimb would reduce the increase in blood pressure and renal sympathetic nerve activity (RSNA) evoked in response to 30 s of static hindlimb skeletal muscle stretch (a model of isolated mechanoreflex activation) in decerebrate, unanaesthetized HF-rEF rats but not sham-operated control rats (SHAM).

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Key Points: Oral sulphonylureas, widely prescribed for diabetes, inhibit pancreatic ATP-sensitive K (K ) channels to increase insulin release. However, K channels are also located within vascular (endothelium and smooth muscle) and muscle (cardiac and skeletal) tissue. We evaluated left ventricular function at rest, maximal aerobic capacity ( O max) and submaximal exercise tolerance (i.

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