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1.
Pediatr Cardiol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38942985

RESUMO

Congenital heart disease (CHD) is one of today's leading birth anomalies. Children with CHD are at risk for adaptive functioning challenges. Sleep difficulties are also common in children with CHD. Indeed, sleep-disordered breathing, a common type of sleep dysfunction, is associated with increased mortality for infants with CHD. The present study examined the associations between adaptive functioning and sleep quality (i.e., duration and disruptions) in children with CHD (n = 23) compared to healthy children (n = 38). Results demonstrated associations between mean hours slept and overall adaptive functioning in the CHD group r(21) = .57, p = .005 but not in the healthy group. The CHD group demonstrated lower levels of adaptive functioning in the Conceptual, t(59) = 2.12, p = .039, Cohen's d = 0.53 and Practical, t(59) = 2.22, p = .030, Cohen's d = 0.55 domains, and overall adaptive functioning (i.e., General Adaptive Composite) nearing statistical significance in comparison to the healthy group, t(59) = 2.00, p = .051, Cohen's d = 0.51. The CHD group also demonstrated greater time awake at night, t(56) = 2.19, p = .033, Cohen's d = 0.58 and a greater instance of parent-caregiver reported snoring, χ2 (1, N = 60) = 5.25, p = .022, V = .296 than the healthy group. Further exploration of the association between adaptive functioning and sleep quality in those with CHD is required to inform clinical practice guidelines.

2.
Am J Physiol Heart Circ Physiol ; 327(1): H45-H55, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38700474

RESUMO

Patients with heart failure with reduced ejection fraction (HFrEF) have exaggerated sympathoexcitation and impaired peripheral vascular conductance. Evidence demonstrating consequent impaired functional sympatholysis is limited in HFrEF. This study aimed to determine the magnitude of reduced limb vascular conductance during sympathoexcitation and whether functional sympatholysis would abolish such reductions in HFrEF. Twenty patients with HFrEF and 22 age-matched controls performed the cold pressor test (CPT) [left foot 2-min in -0.5 (1)°C water] alone and with right handgrip exercise (EX + CPT). Right forearm vascular conductance (FVC), forearm blood flow (FBF), and mean arterial pressure (MAP) were measured. Patients with HFrEF had greater decreases in %ΔFVC and %ΔFBF during CPT (both P < 0.0001) but not EX + CPT (P = 0.449, P = 0.199) compared with controls, respectively. %ΔFVC and %ΔFBF decreased from CPT to EX + CPT in patients with HFrEF (both P < 0.0001) and controls (P = 0.018, P = 0.015), respectively. MAP increased during CPT and EX + CPT in both groups (all P < 0.0001). MAP was greater in controls than in patients with HFrEF during EX + CPT (P = 0.025) but not CPT (P = 0.209). In conclusion, acute sympathoexcitation caused exaggerated peripheral vasoconstriction and reduced peripheral blood flow in patients with HFrEF. Handgrip exercise abolished sympathoexcitatory-mediated peripheral vasoconstriction and normalized peripheral blood flow in patients with HFrEF. These novel data reveal intact functional sympatholysis in the upper limb and suggest that exercise-mediated, local control of blood flow is preserved when cardiac limitations that are cardinal to HFrEF are evaded with dynamic handgrip exercise.NEW & NOTEWORTHY Patients with HFrEF demonstrate impaired peripheral blood flow regulation, evidenced by heightened peripheral vasoconstriction that reduces limb blood flow in response to physiological sympathoexcitation (cold pressor test). Despite evidence of exaggerated sympathetic vasoconstriction, patients with HFrEF demonstrate a normal hyperemic response to moderate-intensity handgrip exercise. Most importantly, acute, simultaneous handgrip exercise restores normal limb vasomotor control and vascular conductance during acute sympathoexcitation (cold pressor test), suggesting intact functional sympatholysis in patients with HFrEF.


Assuntos
Exercício Físico , Antebraço , Força da Mão , Insuficiência Cardíaca , Volume Sistólico , Sistema Nervoso Simpático , Vasoconstrição , Humanos , Masculino , Sistema Nervoso Simpático/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Pessoa de Meia-Idade , Antebraço/irrigação sanguínea , Idoso , Fluxo Sanguíneo Regional , Estudos de Casos e Controles , Função Ventricular Esquerda , Temperatura Baixa , Pressão Arterial , Descanso
3.
Am J Physiol Regul Integr Comp Physiol ; 326(5): R346-R356, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38406844

RESUMO

The aim of this study was to investigate how aging affects blood flow and structure of the brain. It was hypothesized older individuals would have lower gray matter volume (GMV), resting cerebral blood flow (CBF0), and depressed responses to isometabolic and neurometabolic stimuli. In addition, increased carotid-femoral pulse-wave velocity (PWV), carotid intima-media thickness (IMT), and decreased brachial flow-mediated dilation (FMD) would be associated with lower CBF0, cerebrovascular reactivity (CVR), and GMV. Brain scans (magnetic resonance imaging) and cardiovascular examinations were conducted in young (age = 24 ± 3 yr, range = 22-28 yr; n = 13) and old (age = 71 ± 4 yr; range = 67-82 yr, n = 14) participants, and CBF0, CVR [isometabolic % blood oxygen level-dependent (BOLD) in response to a breath hold (BH)], brain activation patterns during a working memory task (neurometabolic %BOLD response to N-back trial), GMV, PWV, IMT, and FMD were measured. CBF0 and to a lesser extent CVRBH were lower in the old group (P ≤ 0.050); however, the increase in the %BOLD response to the memory task was not blunted (P ≥ 0.2867). Age-related differential activation patterns during the working memory task were characterized by disinhibition of the default mode network in the old group (P < 0.0001). Linear regression analyses revealed PWV, and IMT were negatively correlated with CBF0, CVRBH, and GMV across age groups, but within the old group alone only the relationships between PWV-CVRBH and IMT-GMV remained significant (P ≤ 0.0183). These findings suggest the impacts of age on cerebral %BOLD responses are stimulus specific, brain aging involves alterations in cerebrovascular and possibly neurocognitive control, and arterial stiffening and wall thickening may serve a role in cerebrovascular aging.NEW & NOTEWORTHY Cerebral perfusion was lower in old versus young adults. %Blood oxygen level-dependent (BOLD) responses to an isometabolic stimulus and gray matter volume were decreased in old versus young adults and associated with arterial stiffening and wall thickening. The increased %BOLD response to a neurometabolic stimulus appeared unaffected by age; however, the old group displayed disinhibition of the default mode network during the stimulus. Thus, age-related alterations in cerebral %BOLD responses were stimulus specific and related to arterial remodeling.


Assuntos
Espessura Intima-Media Carotídea , Imageamento por Ressonância Magnética , Adulto Jovem , Humanos , Adulto , Idoso , Imageamento por Ressonância Magnética/métodos , Encéfalo/fisiologia , Envelhecimento , Circulação Cerebrovascular/fisiologia , Atrofia
4.
Am J Physiol Heart Circ Physiol ; 326(5): H1105-H1116, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38391313

RESUMO

Whether cerebral sympathetic-mediated vasomotor control can be modulated by local brain activity remains unknown. This study tested the hypothesis that the application or removal of a cognitive task during a cold pressor test (CPT) would attenuate and restore decreases in cerebrovascular conductance (CVC), respectively. Middle cerebral artery blood velocity (transcranial Doppler) and mean arterial pressure (finger photoplethysmography) were examined in healthy adults (n = 16; 8 females and 8 males) who completed a control CPT, followed by a CPT coupled with a cognitive task administered either 1) 30 s after the onset of the CPT and for the duration of the CPT or 2) at the onset of the CPT and terminated 30 s before the end of the CPT (condition order was counterbalanced). The major finding was that the CPT decreased the index of CVC, and such decreases were abolished when a cognitive task was completed concurrently and restored when the cognitive task was removed. As a secondary experiment, vasomotor interactions between sympathetic transduction pathways (α1-adrenergic and Y1-peptidergic) and compounds implicated in cerebral blood flow control [adenosine, and adenosine triphosphate (ATP)] were explored in isolated porcine cerebral arteries (wire myography). The data reveal α1-receptor agonism potentiated vasorelaxation modestly in response to adenosine, and preexposure to ATP attenuated contractile responses to α1-agonism. Overall, the data suggest a cognitive task attenuates decreases in CVC during sympathoexcitation, possibly related to an interaction between purinergic and α1-adrenergic signaling pathways.NEW & NOTEWORTHY The present study demonstrates that the cerebrovascular conductance index decreases during sympathoexcitation and this response can be positively and negatively modulated by the application or withdrawal of a nonexercise cognitive task. Furthermore, isolated vessel experiments reveal that cerebral α1-adrenergic agonism potentiates adenosine-mediated vasorelaxation and ATP attenuates α1-adrenergic-mediated vasocontraction.


Assuntos
Trifosfato de Adenosina , Simpatolíticos , Adulto , Masculino , Feminino , Humanos , Animais , Suínos , Velocidade do Fluxo Sanguíneo/fisiologia , Adrenérgicos , Adenosina/farmacologia , Circulação Cerebrovascular/fisiologia , Pressão Sanguínea/fisiologia , Temperatura Baixa
5.
J Anim Sci ; 1012023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37880833

RESUMO

Heart disease is the leading cause of death in humans and evidence suggests early life growth-restriction increases heart disease risk in adulthood. Therefore, this study sought to investigate the effects of low birth weight (LBW) and postnatal restricted nutrition (RN) on cardiac function in neonatal pigs. We hypothesized that LBW and RN would reduce cardiac function in pigs but this effect would be reversed with refeeding. To investigate this hypothesis, pigs born weighing <1.5 kg were assigned LBW, and pigs born >1.5 kg were assigned normal birth weight (NBW). Half the LBW and NBW pigs underwent ~25% total nutrient restriction via intermittent suckling (assigned RN) for the first 4 wk post-farrowing. The other half of piglets were allowed unrestricted suckling access to the sow (assigned NN). At 28 d of age (weaning), pigs were weaned and provided ad libitum access to a standard diet. Echocardiographic, vascular ultrasound, and blood pressure (BP) measurements were performed on day 28 and again on day 56 to assess cardiovascular structure and function. A full factorial three-way ANOVA (NN vs. RN, LBW vs. NBW, male vs. female) was performed. Key findings include reduced diastolic BP (P = 0.0401) and passive ventricular filling (P = 0.0062) in RN pigs at 28 d but this was reversed after refeeding. LBW piglets have reduced cardiac output index (P = 0.0037) and diastolic and systolic wall thickness (P = 0.0293 and P = 0.0472) at 56 d. Therefore, cardiac dysfunction from RN is recovered with adequate refeeding while LBW programs irreversible cardiac dysfunction despite proper refeeding in neonatal pigs.


Heart disease is the leading cause of death in humans, and in addition to the known modifiable risk factors, evidence suggests early life undernutrition increases heart disease risk in adulthood. Specifically, low birth weight (LBW) has been linked to poor infant cardiac development which could be made worse by an inadequate postnatal diet. Globally, 160 million children under the age of five experience a poor nutritive environment leading to growth-restriction highlighting the need for continued research. Using a pig model, the present investigation examined the effects of LBW and a restricted diet during postnatal life on cardiac structure and function in preweaning and post-weaning piglets. The most important findings were (1) nutrient-restricted piglets had reduced cardiac function at 28 d old but refeeding reversed cardiac dysfunction at 56 d, indicating that nutrient-induced cardiac dysfunction can be reversed, and (2) LBW pigs presented with cardiac dysfunction at 56 d regardless of feeding level, suggesting potential for an increased risk of heart disease in adulthood with LBW.


Assuntos
Cardiopatias , Doenças dos Suínos , Suínos , Animais , Feminino , Masculino , Humanos , Recém-Nascido , Peso ao Nascer/fisiologia , Recém-Nascido de Baixo Peso/fisiologia , Cardiopatias/veterinária
6.
J Appl Physiol (1985) ; 135(6): 1300-1311, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37883101

RESUMO

Slow heart rate recovery following exercise may be influenced by persistent sympathoexcitation. This study examined 1) the effect of muscle metaboreflex activation (MMA) on heart rate recovery following dynamic exercise; and 2) whether the effect of MMA on heart rate recovery is reversible by reducing sympathoexcitation [baroreflex activation via phenylephrine (PE)] in canines. Twenty-two young adults completed control and MMA protocols during cycle ergometry at 110% ventilatory threshold with 5 min recovery. Heart rate recovery kinetics [tau (τ), amplitude, end-exercise, and end-recovery heart rate] and root mean square of successive differences (RMSSD) were measured. Five chronically instrumented canines completed control, MMA (50%-60% imposed reduction in hindlimb blood flow), and MMA with end-exercise PE infusion (MMA + PE) protocols during moderate exercise (6.4 km·h-1) and 3 min recovery. Heart rate recovery kinetics and MAP were measured. MAP increased during MMA versus control in canines (P < 0.001). Heart rate recovery τ was slower during MMA versus control in humans (17% slower; P = 0.011) and canines (150% slower; P = 0.002). Heart rate recovery τ was faster during MMA + PE versus MMA (40% faster; P = 0.034) and was similar to control in canines (P = 0.426). Amplitude, end-exercise, and end-recovery heart rate were similar between conditions in humans (all P ≥ 0.122) and in canines (all P ≥ 0.084). MMA decreased RMSSD in early recovery (P = 0.004). MMA-induced sympathoexcitation slows heart rate recovery and this effect is markedly attenuated with PE. Therefore, elevated sympathoexcitation via MMA impairs heart rate recovery and inhibition of this stimulus normalizes, in part, heart rate recovery.NEW & NOTEWORTHY Augmented sympathoexcitation, via muscle metaboreflex activation, functionally slows heart rate recovery in both young healthy adults and chronically instrumented canines. Furthermore, elevated sympathoexcitation corresponded with lower parasympathetic activity, as assessed by heart rate variability, during the first 3 min of recovery. Finally, sympathoinhibition, via phenylephrine infusion, normalizes heart rate recovery during muscle metaboreflex activation.


Assuntos
Pressão Arterial , Reflexo , Adulto Jovem , Humanos , Animais , Cães , Frequência Cardíaca/fisiologia , Reflexo/fisiologia , Pressão Arterial/fisiologia , Débito Cardíaco/fisiologia , Músculo Esquelético/fisiologia , Fenilefrina , Pressão Sanguínea
7.
Front Vet Sci ; 10: 1183301, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37565080

RESUMO

Introduction: In 2018 the US Food and Drug Administration reported a potential link between grain-free, legume-containing dog foods and the development of canine dilated cardiomyopathy in atypical breeds. One hypothesis was that high oligosaccharide content in legumes reduced bioavailability of taurine, an amino acid with some previous links to canine dilated cardiomyopathy. Methods: To address this hypothesis, in the present study, 8 Beagle dogs consumed four diets: a husbandry commercial dental diet, and three test diets formulated with either 30% rice (control), 30% pea (grain-free) or 30% rice with the addition of 1% raffinose (the predominant oligosaccharide found in peas). The study was conducted in a randomized, crossover design with 5 week feeding periods. Measurement of basic health parameters (weight, body condition score, complete blood cell count, chemistry panel), plasma amino acids, cardiac biomarkers (plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac-specific troponin I), fecal bile acids and echocardiographic exams were completed pre-study after feeding the husbandry diet as well as after each test feeding period. Results: Echocardiography showed 9-11% reduction in ejection fraction and 17- 20% greater left ventricular end systolic volume with the husbandry diet compared to both grain-containing test diets. Concentrations of plasma NT-proBNP were 1.3-2 times greater after the husbandry diet compared to the grain-based diet, with the oligosaccharide and pea-based diets showing intermediate levels. Plasma taurine levels were unchanged across diets, while plasma methionine levels were highest and cysteine/cystine levels were lowest after dogs ate the husbandry diet. Discussion: Results indicate that raffinose in the diet is sufficient, but not required to see an increase NT-proBNP, but did not induce any changes in cardiac function after 5 weeks of feeding. Whether this could progress to reduction in cardiac function with longer term feeding is uncertain. A reduced cardiac function along with the greatest increase in NT-proBNP was observed after feeding the husbandry diet that contained the highest amount of insoluble fiber but did not contain legumes or oligosaccharide. Further research into the impact of insoluble fiber in the dental diet is needed to support these novel observations.

8.
J Appl Physiol (1985) ; 135(2): 279-291, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37348013

RESUMO

Heart failure with reduced ejection fraction (HFrEF) exhibits exaggerated sympathoexcitation and altered cardiac and vascular responses to muscle metaboreflex activation (MMA). However, left ventricular (LV) responses to MMA are not well studied in patients with HFrEF. The purpose of this study was to examine LV function during MMA using cardiac magnetic resonance imaging (MRI) in patients with HFrEF. Thirteen patients with HFrEF and 18 healthy age-matched controls underwent cardiac MRI during rest and MMA. MMA protocol included 6 min of isometric handgrip exercise followed by 6-min of brachial postexercise circulatory occlusion. LV stroke volume index (SVi), end-systolic volume index (ESVi), end-diastolic volume index (EDVi), and global longitudinal strain (GLS) were measured by two- and four-chamber cine images. Volumes were indexed to body surface area. Heart rate (via ECG) and brachial mean arterial pressure (MAP) were recorded. Cardiac output and total peripheral resistance (TPR) were calculated. SVi decreased during MMA in HFrEF (P = 0.037) but not in controls (P = 0.392). ESVi (P = 0.007) and heart rate (P < 0.001) increased during MMA in HFrEF but not controls (P ≥ 0.170). TPR (P = 0.021) and MAP (P < 0.001) increased during MMA in both groups. Cardiac output (P = 0.946), EDVi (P = 0.177), and GLS (P = 0.619) were maintained from rest to MMA in both groups. Despite similarly maintained cardiac output, LV strain, and increased TPR in HFrEF and control groups, SVi decreased, and heart rate increased during MMA in patients with HFrEF. These findings suggest an impaired contractility reserve in response to increased TPR during MMA in HFrEF.NEW & NOTEWORTHY Stroke volume decreases and end-systolic volume increases during muscle metaboreflex activation in patients with heart failure with reduced ejection fraction (HFrEF), suggesting impaired contractile reserve during muscle metaboreflex activation in patients with HFrEF. Total peripheral resistance increases similarly during muscle metaboreflex activation in patients with HFrEF compared to controls, indicating normal levels of peripheral vasoconstriction during muscle metaboreflex activation in patients with HFrEF.


Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Humanos , Volume Sistólico/fisiologia , Reflexo/fisiologia , Força da Mão , Pressão Arterial/fisiologia , Músculo Esquelético/fisiologia , Função Ventricular Esquerda
9.
Microvasc Res ; 148: 104550, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37230164

RESUMO

Using swine as an experimental model, we examined whether the cannabinoid receptors (CB1R and CB2R) modulated vasomotor tone in isolated pial arteries. It was hypothesized that the CB1R would mediate cerebral artery vasorelaxation in an endothelial-dependent manner. First-order pial arteries were isolated from female Landrace pigs (age = 2 months; N = 27) for wire and pressure myography. Arteries were pre-contracted with a thromboxane A2 analogue (U-46619) and vasorelaxation in response to the CB1R and CB2R receptor agonist CP55940 was examined in the following conditions: 1) untreated; 2) inhibition of the CB1R (AM251); or 3) inhibition of the CB2R receptor (AM630). The data revealed that CP55940 elicits a CB1R-dependent relaxation in pial arteries. CB1R expression was confirmed using immunoblot and immunohistochemical analyses. Subsequently, the role of different endothelial-dependent pathways in the CB1R-mediated vasorelaxation was examined using: 1) denudation (removal of the endothelium); 2) inhibition of cyclooxygenase (COX; Naproxen); 3) inhibition of nitric oxide synthase (NOS; L-NAME); and 4) combined inhibition of COX + NOS. The data revealed CB1R-mediated vasorelaxation was endothelial-dependent, with contributions from COX-derived prostaglandins, NO, and endothelium-dependent hyperpolarizing factor (EDHF). Pressurized arteries underwent myogenic curves (20-100 mmHg) under the following conditions: 1) untreated; 2) inhibition of the CB1R. The data revealed CB1R inhibition increased basal myogenic tone, but not myogenic reactivity. As the vascular responses were assessed in isolated pial arteries, this work reveals that the CB1R modulates cerebrovascular tone independently of changes in brain metabolism.


Assuntos
Cicloexanóis , Óxido Nítrico , Vasodilatação , Animais , Feminino , Artérias Cerebrais/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico/metabolismo , Suínos , Cicloexanóis/farmacologia
10.
Am J Physiol Regul Integr Comp Physiol ; 324(3): R293-R304, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36622084

RESUMO

Vascular insulin resistance, a major characteristic of obesity and type 2 diabetes (T2D), manifests with blunting of insulin-induced vasodilation. Although there is evidence that females are more whole body insulin sensitive than males in the healthy state, whether sex differences exist in vascular insulin sensitivity is unclear. Also uncertain is whether weight loss can reestablish vascular insulin sensitivity in T2D. The purpose of this investigation was to 1) establish if sex differences in vasodilatory responses to insulin exist in absence of disease, 2) determine whether female sex affords protection against the development of vascular insulin resistance with long-term overnutrition and obesity, and 3) examine if diet-induced weight loss can restore vascular insulin sensitivity in men and women with T2D. First, we show in healthy mice and humans that sex does not influence insulin-induced femoral artery dilation and insulin-stimulated leg blood flow, respectively. Second, we provide evidence that female mice are protected against impairments in insulin-induced dilation caused by overnutrition-induced obesity. Third, we show that men and women exhibit comparable levels of vascular insulin resistance when T2D develops but that diet-induced weight loss is effective at improving insulin-stimulated leg blood flow, particularly in women. Finally, we provide indirect evidence that these beneficial effects of weight loss may be mediated by a reduction in endothelin-1. In aggregate, the present data indicate that female sex confers protection against obesity-induced vascular insulin resistance and provide supportive evidence that, in women with T2D, vascular insulin resistance can be remediated with diet-induced weight loss.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Feminino , Masculino , Camundongos , Animais , Resistência à Insulina/fisiologia , Insulina , Obesidade , Redução de Peso , Artéria Femoral , Dieta
11.
J Diabetes Complications ; 37(1): 108365, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463707

RESUMO

The etiology of insulin resistance (IR) in Type 1 Diabetes (T1D) is unclear; however, intramyocellular lipids (IMCL) are likely contributors. While exercise lessens IR and IMCL content; T1D patients elevate glycemia to offset exercise-induced hypoglycemic risk. The preferred treatment for T1D patients is tight glucose management through intensive insulin therapy (IIT); however, IIT is accompanied with a sedentary lifestyle. The purpose of this study was to examine IR development and IMCL in combined exercise (DARE; aerobic/resistance) and IIT-treated T1D animals. 76 rats were divided into control sedentary (C), diabetic sedentary (CD), diabetes sedentary intensive insulin therapy (DIT) and DARE groups. Following streptozotocin (STZ), glycemia was maintained at either 9-15 mM (CD, DARE) or 5-9 mM (DIT) using insulin. DARE alternated between running and weighted climbing for 12 weeks. Results demonstrate that DARE exhibited reduced onset of IR compared with C, DIT and CD, indicated by increased glucose infusion rate (hyperinsulinemic-euglycemic-clamp). A shift in lipid metabolism was evident whereby diacylglycerol was elevated in DIT compared to DARE, while triacylglycerol was elevated in DARE. These findings indicate enhanced IMCL metabolism and the sequestration of fat as neutral triacylglycerol leads to reduced IR in DARE. In contrast, IIT and sedentary behavior leads to diacylglycerol accumulation and IR.


Assuntos
Diabetes Mellitus Tipo 1 , Exercício Físico , Resistência à Insulina , Insulina , Animais , Ratos , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/terapia , Diglicerídeos/metabolismo , Glucose/metabolismo , Insulina/uso terapêutico , Insulina/metabolismo , Insulina Regular Humana , Metabolismo dos Lipídeos , Músculo Esquelético/metabolismo , Triglicerídeos , Exercício Físico/fisiologia , Modelos Animais de Doenças
12.
Front Mol Neurosci ; 16: 1320879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38163062

RESUMO

Diet-induced obesity is implicated in the development of a variety of neurodegenerative disorders. Concurrently, the loss of mitochondrial Complex I protein or function is emerging as a key phenotype across an array of neurodegenerative disorders. Therefore, the objective of this study was to determine if Western diet (WD) feeding in swine [carbohydrate = 40.8% kCal (17.8% of total calories from high fructose corn syrup), protein = 16.2% kcal, fat = 42.9% kCal, and 2% cholesterol] would result in Complex I syndrome pathology. To characterize the effects of WD-induced obesity on brain mitochondria in swine, high resolution respirometry measurements from isolated brain mitochondria, oxidative phosphorylation Complex expression, and indices of oxidative stress and mitochondrial biogenesis were assessed in female Ossabaw swine fed a WD for 6-months. In line with Complex I syndrome, WD feeding severely reduced State 3 Complex I, State 3 Complex I and II, and uncoupled mitochondrial respiration in the hippocampus and prefrontal cortex (PFC). State 3 Complex I mitochondrial respiration in the PFC inversely correlated with serum total cholesterol. WD feeding also significantly reduced protein expression of oxidative phosphorylation Complexes I-V in the PFC. WD feeding significantly increased markers of antioxidant defense and mitochondrial biogenesis in the hippocampi and PFC. These data suggest WD-induced obesity may contribute to Complex I syndrome pathology by increasing oxidative stress, decreasing oxidative phosphorylation Complex protein expression, and reducing brain mitochondrial respiration. Furthermore, these findings provide mechanistic insight into the clinical link between obesity and mitochondrial Complex I related neurodegenerative disorders.

13.
Resusc Plus ; 12: 100326, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36407570

RESUMO

Introduction: During cardiopulmonary resuscitation (CPR), high quality chest compressions are critical to organ perfusion, especially the brain. Yet, the optimal location for chest compressions is unclear. It was hypothesized that compared with the standard chest compression (SCC) location, left ventricle chest compressions (LVCCs) would result in greater ETCO2, blood pressure (BP), and cerebral blood velocity (CBV) during CPR in swine. Methods: Female Landrace swine (N = 32; 35 ± 2 kg) underwent two mins of untreated asphyxiated cardiac arrest (CA). Thereafter, swine were treated with three 2-min cycles of either SCC or LVCC mechanical basic life support CPR (LUCAS 3). ETCO2 (in-line sampling), BP (arterial catheter line), and CBV (transcranial Doppler) were measured during the pre-CA, untreated-CA, and CPR-treated phases. Results: ETCO2, BP, and CBV were similar between groups at pre- and during untreated-CA (P ≥ 0.188). During CPR, ETCO2 (36 ± 6 versus 24 ± 10 mmHg, P < 0.001), mean arterial BP (MAP; 49 ± 9 versus 37 ± 9 mmHg, P = 0.002), and CBV (11 ± 5 versus 5 ± 2 cm/s, P < 0.001) were significantly greater in the LVCC versus SCC group. Moreover, a greater proportion of animals obtained targets for ETCO2 (ETCO2 ≥ 20 mmHg; 52 % (17/33) versus 100 % (32/32), P < 0.001) and diastolic BP (DBP ≥ 25 mmHg; 82 % (33/40) versus 97 % (48/49), P = 0.020) in the LVCC versus SCC group. Conclusion: Indicators of cardiac output, BP, and cerebral perfusion during CPR were greatest in the LVCC group, suggesting the quality of chest compressions during BLS CPR may be improved by performing compressions over the left ventricle compared to the centre of the chest.

14.
J Appl Physiol (1985) ; 133(5): 1228-1236, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36227166

RESUMO

Myogenic and flow-induced reactivity contribute to cerebral autoregulation, with potentially divergent roles for smaller versus larger arteries. The present study tested the hypotheses that compared with first-order (1A) branches of the middle cerebral artery, second- and third-order branches (2A and 3A, respectively) exhibit greater myogenic reactivity but reduced flow-induced constriction. Furthermore, nitric oxide synthase (NOS) inhibition may amplify myogenic reactivity and abolish instances of flow-induced dilation. Isolated porcine cerebral arteries mounted in a pressure myograph were exposed to incremental increases in intraluminal pressure (40-120 mmHg; n = 41) or flow (1-1,170 µL/min; n = 31). Intraluminal flows were adjusted to achieve 5, 10, 20, and 40 dyn/cm2 of wall shear stress at 60 mmHg. Myogenic tone was greater in 3A versus 1A arteries (P < 0.05). There was an inverse relationship between myogenic reactivity and passive arterial diameter (P < 0.01). NOS inhibition increased basal tone to a lesser extent in 3A versus 1A arteries (P < 0.01) but did not influence myogenic reactivity (P = 0.49). Increasing flow decreased luminal diameter (P ≤ 0.01), with increased vasoconstriction at 10-40 dyn/cm2 of shear stress (P < 0.01). However, relative responses were similar between 1A, 2A, and 3A arteries (P = 0.40) with and without NOS inhibition conditions (P ≥ 0.29). Whereas NOS inhibition increases basal myogenic tone, and myogenic reactivity was less in smaller versus larger arteries (range = ∼100-550 µM), neither NOS inhibition nor luminal diameter influences flow-induced constriction in porcine cerebral arteries.NEW & NOTEWORTHY This study demonstrated size-dependent heterogeneity in myogenic reactivity in porcine cerebral arteries. Smaller branches of the middle cerebral artery exhibited increased myogenic reactivity, but attenuated NOS-dependent increases in myogenic tone compared with larger branches. Flow-dependent regulation does not exhibit the same variation; diameter-independent flow-induced vasoconstrictions occur across all branch orders and are not affected by NOS inhibition. Conceptually, flow-induced vasoconstriction contributes to cerebral autoregulation, particularly in larger arteries with low myogenic tone.


Assuntos
Artéria Cerebral Média , Óxido Nítrico , Suínos , Animais , Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase , Vasoconstrição/fisiologia
15.
Physiol Rep ; 10(8): e15256, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35439367

RESUMO

The study of vascular regulation often omits important information about the elastic properties of arteries under conditions of pulsatile flow. The purpose of this study was to examine the relationship between muscle sympathetic nerve activity (MSNA), vascular bed compliance, and peripheral blood flow responses in humans. We hypothesized that increases in MSNA would correlate with reductions in vascular compliance, and that changes in compliance would correspond with changes in peripheral blood flow during sympatho-excitation. MSNA (microneurography), blood pressure (Finopres), and brachial artery blood flow (Doppler ultrasound), were monitored in six healthy males at baseline and during the last 15 s of voluntary end-inspiratory, expiratory apneas and 5 min of static handgrip exercise (SHG; 20% maximum voluntary contraction) and 3 min of post-exercise circulatory occlusion (SHG + PECO; measured in the non-exercising arm). A lumped Windkessel model was employed to examine vascular bed compliance. During apnea, indices of MSNA were inversely related with vascular compliance, and reductions in compliance correlated with decreased brachial blood flow rate. During SHG, despite increased MSNA, compliance also increased, but was unrelated to increases in blood flow. Neither during SHG nor PECO did indices of MSNA correlate with forearm vascular compliance nor did vascular compliance correlate with brachial flow. However, during PECO, a linear combination of blood pressure and total MSNA was correlated with vascular compliance. These data indicate the elastic components of the forearm vasculature are regulated by adrenergic and myogenic mechanisms during sympatho-excitation, but in a reflex-dependent manner.


Assuntos
Antebraço , Força da Mão , Pressão Sanguínea/fisiologia , Antebraço/irrigação sanguínea , Força da Mão/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Músculo Esquelético/fisiologia , Sistema Nervoso Simpático/fisiologia , Resistência Vascular
16.
J Physiol ; 600(10): 2311-2325, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35389526

RESUMO

Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n = 11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n = 9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n = 11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.


Assuntos
Insuficiência Cardíaca , Isquemia Miocárdica , Disfunção Ventricular Esquerda , Animais , Humanos , Arritmias Cardíacas/complicações , Hemodinâmica , Estudos Retrospectivos , Volume Sistólico/fisiologia , Suínos , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda/fisiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-35151870

RESUMO

Full-term low birthweight (LBW) offspring exhibit peripheral vascular dysfunction in the postnatal period; however, whether such impairments extend to the cerebrovasculature remains to be elucidated. We used a swine model to test the hypothesis that LBW offspring would exhibit cerebrovascular dysfunction at later stages of life. Offspring from 14 sows were identified as normal birthweight (NBW) or LBW and were assessed at 28 (similar to end of infancy) and 56 (similar to childhood) days of age. LBW swine had lower absolute brain mass, but demonstrated evidence of brain sparing (increased brain mass scaled to body mass) at 56 days of age. The cerebral pulsatility index, based on transcranial Doppler, was increased in LBW swine. Moreover, arterial myography of isolated cerebral arteries revealed impaired vasoreactivity to bradykinin and reduced contribution of nitric oxide (NO) to vasorelaxation in the LBW swine. Immunoblotting demonstrated a lower ratio of phosphorylated-to-total endothelial NO synthase in LBW offspring. This impairment in NO signaling was greater at 28 vs. 56 days of age. Vasomotor responses to sodium nitroprusside (NO-donor) were unaltered, while Leu31, Pro34 neuropeptide Y-induced vasoconstriction was enhanced in LBW swine. Increases in total Y1 receptor protein content in the LBW group were not significant. In summary, LBW offspring displayed signs of cerebrovascular dysfunction at 28 and 56 days of age, evidenced by altered cerebral hemodynamics (reflective of increased impedance) coupled with endothelial dysfunction and altered vasomotor control. Overall, the data reveal that normal variance in birthweight of full-term offspring can influence cerebrovascular function later in life.


Assuntos
Artérias , Vasodilatação , Animais , Peso ao Nascer , Encéfalo , Feminino , Nitroprussiato , Suínos
18.
Ultrasound J ; 14(1): 1, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34978635

RESUMO

BACKGROUND: While intra-arrest echocardiography can be used to guide and monitor chest compression quality, it is not currently feasible on the scene of out-of-hospital cardiac arrests. Rapid and automated sonographic localization of the heart may provide first-responders guidance to an optimal area of compression without requiring them to interpret ultrasound images. In this proof-of-concept porcine study, we sought to describe the performance of an automated ultrasound device in correctly identifying and tracing the borders of the heart in three distinct states: pre-arrest, arrest, and late arrest. METHODS: An automated ultrasound device (bladder scanner) was placed on the chests of 7 swine, along the left sternal border (4th-8th intercostal spaces). Scanner-generated images were recorded for each space during pre-arrest, arrest, and finally late arrest. 828 images of the LV and LV outflow tract were randomized and 150 (50/state) selected for analysis. Scanner tracings of the heart were then digitally obscured to facilitate tracing by expert reviewers who were blinded to the physiologic state. Reviewer tracings were compared to bladder scanner tracings; with concordance between these images determined via Sørensen-Dice index (SDI). RESULTS: When compared to human reviewers, the bladder scanner was able to identify and trace the borders during cardiac arrest. The bladder scanner performed best at the time of arrest (SDI 0.900 ± 0.059). As resuscitation efforts continued and time from initial arrest increased, the scanner's performance decreased dramatically (SDI 0.597 ± 0.241 in late arrest). CONCLUSION: An automated ultrasound device (bladder scanner) reliably traced porcine hearts during cardiac arrest. It is possible a device could be developed to indicate where compressions should be performed without requiring the operator to interpret ultrasound images. Further investigation into rapid, automated, sonographic localization of the heart to identify the area of compression in out-of-hospital cardiac arrest is warranted.

19.
Brain Imaging Behav ; 16(4): 1575-1591, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35092574

RESUMO

The purpose of this study was to determine if differences in functional connectivity strength (FCS) with age were confounded by vascular parameters including resting cerebral blood flow (CBF0), cerebrovascular reactivity (CVR), and BOLD-CBF coupling. Neuroimaging data were collected from 13 younger adults (24 ± 2 years) and 14 older adults (71 ± 4 years). A dual-echo resting state pseudo-continuous arterial spin labeling sequence was performed, as well as a BOLD breath-hold protocol. A group independent component analysis was used to identify networks, which were amalgamated into a region of interest (ROI). Within the ROI, FC strength (FCS) was computed for all voxels and compared across the groups. CBF0, CVR and BOLD-CBF coupling were examined within voxels where FCS was different between young and older adults. FCS was greater in old compared to young (P = 0.001). When the effect of CBF0, CVR and BOLD-CBF coupling on FCS was examined, BOLD-CBF coupling had a significant effect (P = 0.003) and group differences in FCS were not present once all vascular parameters were considered in the statistical model (P = 0.07). These findings indicate that future studies of FCS should consider vascular physiological markers in order to improve our understanding of aging processes on brain connectivity.


Assuntos
Circulação Cerebrovascular , Imageamento por Ressonância Magnética , Idoso , Encéfalo/fisiologia , Circulação Cerebrovascular/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Descanso/fisiologia , Marcadores de Spin
20.
JCI Insight ; 6(10)2021 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-34027891

RESUMO

Individuals with heart failure (HF) frequently present with comorbidities, including obesity, insulin resistance, hypertension, and dyslipidemia. Many patients with HF experience cardiogenic dementia, yet the pathophysiology of this disease remains poorly understood. Using a swine model of cardiometabolic HF (Western diet+aortic banding; WD-AB), we tested the hypothesis that WD-AB would promote a multidementia phenotype involving cerebrovascular dysfunction alongside evidence of Alzheimer's disease (AD) pathology. The results provide evidence of cerebrovascular insufficiency coupled with neuroinflammation and amyloidosis in swine with experimental cardiometabolic HF. Although cardiac ejection fraction was normal, indices of arterial compliance and cerebral blood flow were reduced, and cerebrovascular regulation was impaired in the WD-AB group. Cerebrovascular dysfunction occurred concomitantly with increased MAPK signaling and amyloidogenic processing (i.e., increased APP, BACE1, CTF, and Aß40 in the prefrontal cortex and hippocampus) in the WD-AB group. Transcriptomic profiles of the stellate ganglia revealed the WD-AB group displayed an enrichment of gene networks associated with MAPK/ERK signaling, AD, frontotemporal dementia, and a number of behavioral phenotypes implicated in cognitive impairment. These provide potentially novel evidence from a swine model that cerebrovascular and neuronal pathologies likely both contribute to the dementia profile in a setting of cardiometabolic HF.


Assuntos
Amiloide/metabolismo , Transtornos Cerebrovasculares , Insuficiência Cardíaca , Doenças Metabólicas , Animais , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/fisiopatologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/fisiopatologia , Transdução de Sinais , Suínos
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