RESUMO
With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.
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Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Pressão Sanguínea/fisiologia , Hemodinâmica , Artérias , Envelhecimento , Circulação Cerebrovascular/fisiologiaRESUMO
This research examined the impact of aerobic exercise intensity and dose on acute post-exercise cerebral shear stress and blood flow. Fourteen young adults (27 ± 5 years of age, eight females) completed a maximal oxygen uptake ( V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ ) treadmill test followed by three randomized study visits: treadmill exercise at 30% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min, 70% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min and 70% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for a duration that resulted in caloric expenditure equal to that in the 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P = 0.005, condition: P = 0.012) and the increase was greater following exercise at 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆4.1 ± 3.5 dyn/cm2) compared with 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆1.1 ± 1.9 dyn/cm2; P = 0.041). ICA blood flow remained elevated following exercise (time: P = 0.002, condition: P = 0.010) with greater increases after 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (Δ268 ± 150 mL/min) compared with 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆125 ± 149 mL/min; P = 0.041) or 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ EqEE (∆127 ± 177 mL/min; P = 0.004). Therefore, aerobic exercise resulted in both intensity- and dose-dependent effects on acute post-exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.
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This study tested the hypothesis that during fatiguing volitional exercise in humans, descending cortical signals and ascending skeletal muscle metaboreflex signals exert divergent control over baroreflex resetting of sympathetic action potential (AP) discharge. We quantified the baroreflex gain for sympathetic AP clusters within the muscle sympathetic nerve activity neurogram (peroneal microneurography and continuous wavelet transform) during baseline (BSL), the first 2-min of a 5-min isometric handgrip (20% of maximal effort; IHG1), the last 2-min of IHG (IHG2), and during postexercise circulatory occlusion (PECO) in seven healthy participants. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability (%) versus diastolic blood pressure (DBP; mmHg) for 10 normalized AP clusters. Compared with BSL, during IHG1, AP baroreflex threshold functions were only reset to greater DBP and baroreflex gain was unaffected. Compared with BSL, during IHG2 and PECO, baroreflex functions were reset to greater DBP and to greater AP firing probabilities, with medium-sized APs demonstrating the largest upward resetting (e.g., cluster 3 BSL: 26 ± 7%, cluster 3 IHG2: 78 ± 22%, cluster 3 PECO: 88 ± 46%). Compared with BSL, AP baroreflex threshold gain was not different during IHG2 but was increased during PECO, with medium-sized APs demonstrating the largest increase in baroreflex gain (e.g., cluster 3 BSL: -6.31 ± 3.1%/mmHg, cluster 3 IHG2: -6.18 ± 5.4%/mmHg, cluster 3 PECO: -12.13 ± 6.5%/mmHg). These findings indicate that during IHG exercise, descending cortical signaling and ascending skeletal muscle metaboreceptor signals differentially affect baroreflex resetting of subpopulations of human muscle sympathetic postganglionic neurons.NEW & NOTEWORTHY This study provides new insight to baroreflex resetting of MSNA during exercise in humans. Both fatiguing IHG and PECO reset baroreflex control of sympathetic APs to higher blood pressures and greater MSNA. However, only PECO increased baroreflex threshold gain of medium-sized sympathetic APs, an effect that was concealed when focusing on the integrated MSNA neurogram to quantify baroreflex gain. These data suggest that descending central versus ascending muscle metaboreflex mechanisms differentially affect baroreflex resetting of sympathetic APs.
Assuntos
Barorreflexo , Força da Mão , Humanos , Barorreflexo/fisiologia , Potenciais de Ação , Força da Mão/fisiologia , Pressão Sanguínea/fisiologia , Sistema Nervoso Simpático/fisiologia , Músculo Esquelético/fisiologia , Frequência CardíacaRESUMO
Increasing evidence indicates that cerebrovascular compliance contributes to the dynamic regulation of cerebral blood flow but the mechanisms regulating cerebrovascular compliance in humans are unknown. This retrospective study investigated the impact of neural, endothelial, and myogenic mechanisms on the regulation of vascular compliance in the cerebral vascular bed compared with the forearm vascular bed. An index of vascular compliance (Ci) was assessed using a Windkessel model applied to blood pressure waveforms (finger photoplethysmography) and corresponding middle cerebral artery blood velocity or brachial artery blood velocity waveforms (Doppler ultrasound). Data were analyzed during a 5-min baseline period (10 waveforms) under control conditions and during distinct sympathetic blockade (experiment 1, phentolamine; 10 adults), cholinergic blockade (experiment 2, glycopyrrolate; 9 adults), and myogenic blockade (experiment 3, nicardipine; 14 adults). In experiment 1, phentolamine increased Ci similarly in the cerebral vascular bed (131 ± 135%) and forearm vascular bed (93 ± 75%; P = 0.45). In experiment 2, glycopyrrolate increased cerebrovascular Ci (72 ± 61%) and forearm vascular Ci (74 ± 64%) to a similar extent (P = 0.88). In experiment 3, nicardipine increased Ci but to a greater extent in the cerebral vascular bed (88 ± 88%) than forearm vascular bed (20 ± 45%; P = 0.01). Therefore, adrenergic, cholinergic, and myogenic mechanisms contribute to the regulation of cerebrovascular and forearm vascular compliance. However, myogenic mechanisms appear to exert more specific control over vascular compliance in the brain relative to the forearm.NEW & NOTEWORTHY Vascular compliance represents an important determinant in the dynamics and regulation of blood flow through a vascular bed. However, the mechanisms that regulate vascular compliance remain poorly understood. This study examined the impact of neural, endothelial, and myogenic mechanisms on cerebrovascular compliance compared with forearm vascular compliance. Distinct pharmacological blockade of α-adrenergic, endothelial muscarinic, and myogenic inputs altered cerebrovascular and forearm vascular compliance. These results further our understanding of vascular control and blood flow regulation in the brain.
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Antebraço , Nicardipino , Adulto , Humanos , Antebraço/irrigação sanguínea , Fentolamina/farmacologia , Glicopirrolato/farmacologia , Estudos Retrospectivos , Pressão Sanguínea , Circulação Cerebrovascular/fisiologia , Adrenérgicos , Colinérgicos , Fluxo Sanguíneo RegionalRESUMO
Menopause is associated with adverse changes in vascular health coinciding with an increased risk of stroke and vascular cognitive impairment. However, there is significant variation in the age at menopause. The present study examined how the age at natural menopause impacts cerebrovascular reactivity and structural biomarkers of brain aging. Thirty-five healthy postmenopausal women were classified as early-onset menopause (Early; n = 19, age at menopause: 47 ± 2 yr) or later-onset menopause (Late; n = 16, age at menopause: 55 ± 2 yr). Middle cerebral artery blood velocity (MCAv), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) were recorded during a stepped hypercapnia protocol. Reactivity was calculated as the slope of the relationship between ETCO2 and each variable of interest. Brain volumes and white matter hyperintensities (WMHs) were obtained with 3T MRI. Resting MAP was greater in the Early group (99 ± 9 mmHg) compared with the Late group (90 ± 12 mmHg; P = 0.02). Cerebrovascular reactivity, assessed using MCAv, was blunted in the Early group (1.87 ± 0.92 cm/s/mmHg) compared with the Late group (2.37 ± 0.75 cm/s/mmHg; P = 0.02). Total brain volume did not differ between groups (Early: 1.08 ± 0.07 L vs. Late: 1.07 ± 0.06 L; P = 0.66), but the Early group demonstrated greater WMH fraction compared with the Late group (Early: 0.36 ± 0.14% vs. Late: 0.25 ± 0.14%; P = 0.02). These results suggest that age at natural menopause impacts cerebrovascular function and WMH burden in healthy postmenopausal women.
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Encéfalo , Circulação Cerebrovascular , Humanos , Feminino , Circulação Cerebrovascular/fisiologia , Encéfalo/fisiologia , Dióxido de Carbono , Hipercapnia , Menopausa , Velocidade do Fluxo SanguíneoRESUMO
The sympathetic nervous system exhibits patterns of action potential (AP) discharge in human muscle sympathetic nerve activity that suggest coding strategies express reflex specificity. This study explored the interactive effects of baroreceptor unloading using lower body negative pressure (LBNP) and volitional end-expiratory apnea (APN) on sympathetic postganglionic neuronal discharge patterns inferred from the firing patterns of differently sized sympathetic AP clusters. Seven individuals were studied using multiunit microneurography (fibular) and a continuous wavelet approach to quantify AP discharge probability, recruitment, and latency during APN performed under ambient conditions, -10, and -40 mmHg LBNP. Compared with the ambient condition, LBNP increased AP discharge rate at -10 and -40 mmHg and recruited larger previously silent sympathetic neurons at -40 mmHg. Compared with spontaneous breathing, APN increased AP discharge when performed during the ambient condition (Δ351 ± 132 AP/min), -10 mmHg (Δ423 ± 184 AP/min), and -40 mmHg (Δ355 ± 278 AP/min; main effect APN: P < 0.01; LBNP-by-APN interaction: P = 0.55). APN recruited larger previously silent AP clusters during the ambient condition (Δ4 ± 3; P < 0.02) and -10 mmHg (Δ4 ± 3; P < 0.01), but not -40 mmHg (Δ0 ± 2; P = 0.53; LBNP-by-APN: P < 0.01). LBNP did not affect AP latency. However, APN reduced AP latency similarly during all conditions (ambient pressure: Δ-0.04 ± 0.04s, -10 mmHg: Δ-0.03 ± 0.03s, -40 mmHg: Δ-0.03 ± 0.04s; main effect APN: P < 0.01; LBNP-by-APN: P = 0.48). These data indicate that apneic and baroreflex mechanisms appear to additively modify the axonal discharge rate of previously active sympathetic postganglionic neurons and interact to affect recruitment of previously silent sympathetic neurons. Reductions in AP latency due to apneic stress were not impacted by baroreflex unloading.NEW & NOTEWORTHY Discrete physiological stressors differentially affect sympathetic postganglionic neuronal rate-, population-, and temporal-coding strategies. When performing end-expiratory apnea (APN) during graded baroreflex unloading via lower body negative pressure (LBNP), we found: 1) augmented sympathetic axonal firing probability, 2) recruitment of larger and previously silent sympathetic postganglionic neurons at ambient and -10 mmHg, but not -40 mmHg LBNP, and 3) APN reduced axonal discharge latency similarly across all conditions, independent of the level of baroreflex unloading.
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Apneia , Barorreflexo , Pressão Sanguínea , Frequência Cardíaca , Humanos , Músculos , Neurônios , Sistema Nervoso Simpático/fisiologiaRESUMO
NEW FINDINGS: What is the central question of this study? Vascular compliance importantly contributes to the regulation of cerebral perfusion and complex mechanisms are known to influence compliance of a vascular bed: while vasodilatation mediates changes in vascular resistance, does it also affect compliance, particularly in the cerebral vasculature? What is the main finding and its importance? Cerebral vasodilatation, elicited by hypercapnia and sodium nitroglycerin administration, reduced cerebrovascular compliance by approximately 26% from baseline. This study provides new insight into mechanisms mediating cerebrovascular compliance. ABSTRACT: Changes in vascular resistance and vascular compliance contribute to the regulation of cerebral perfusion. While changes in vascular resistance are known to be mediated by vasodilatation, the mechanisms contributing to changes in vascular compliance are complex. In particular, whether vasodilatation affects compliance of the vasculature within the cranium remains unknown. Therefore, the present study examined the impact of two vasodilatation pathways on cerebrovascular compliance in humans. Fifteen young, healthy adults (26 ± 5 years, seven females) completed two protocols: (i) sublingual sodium nitroglycerin (SNG; 0.4 mg) and (ii) hypercapnia (5-6% carbon dioxide gas mixture for 4 min). Blood pressure waveforms (finger photoplethysmography) and middle cerebral artery blood velocity waveforms (transcranial Doppler ultrasound) were input into a modified Windkessel model and an index of cerebrovascular compliance (Ci) was calculated. During the SNG protocol, Ci decreased 24 ± 17% from baseline ((5.0 ± 2.3) × 10-4 cm s-1 mmHg-1 ) to minute 10 ((3.6 ± 1.2) × 10-4 cm s-1 mmHg-1 ; P = 0.009). During the hypercapnia protocol, Ci decreased 28 ± 9% from baseline ((4.4 ± 1.9) × 10-4 cm s-1 mmHg-1 ) to minute 4 ((3.1 ± 1.4) × 10-4 cm s-1 mmHg-1 ; P < 0.001). Cerebral vasodilatory stimuli induced by nitric oxide and carbon dioxide mechanisms reduced compliance of the cerebral vascular bed by approximately 26% from supine baseline values.
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Dióxido de Carbono , Nitroglicerina , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Artérias Cerebrais , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Hipercapnia , Artéria Cerebral Média , Nitroglicerina/farmacologia , Sódio , VasodilataçãoRESUMO
KEY POINTS: Emission patterns in muscle sympathetic nerve activity stem from differently sized action potential (AP) subpopulations that express varying discharge probabilities. The mechanisms governing these firing behaviours are unclear. This study investigated the hypothesis that the arterial baroreflex exerts varying control over the different AP subpopulations. During baseline, medium APs expressed the greatest baroreflex slopes, while small and large APs exhibited weaker slopes. On going from baseline to lower body negative pressure (LBNP; simulated orthostatic stress), baroreflex slopes for some clusters of medium APs expressed the greatest increase, while slopes for large APs also increased but to a lesser degree. A subpopulation of previously silent larger APs was recruited with LBNP but these APs expressed weak baroreflex slopes. The arterial baroreflex heterogeneously regulates sympathetic AP subpopulations, exerting its strongest effect over medium APs. Weak baroreflex mechanisms govern the recruitment of latent larger AP subpopulations during orthostatic stress. ABSTRACT: Muscle sympathetic nerve activity (MSNA) occurs primarily in bursts of action potentials (AP) with subpopulations that differ in size and discharge probabilities. The mechanisms determining these discharge patterns remain unclear. This study investigated the hypothesis that variations in AP discharge are due to subpopulation-specific baroreflex control. We employed multi-unit microneurography and a continuous wavelet analysis approach to extract sympathetic APs in 12 healthy individuals during baseline (BSL) and lower body negative pressure (LBNP; -40, -60, -80 mmHg). For each AP cluster, the baroreflex threshold slope was measured from the linear regression between AP probability (%) and diastolic blood pressure (mmHg). During BSL, the baroreflex exerted non-uniform regulation over AP subpopulations: medium-sized AP clusters expressed the greatest slopes while clusters of small and large APs expressed weaker slopes. On going from BSL to LBNP, the baroreflex slopes for each AP subpopulation were modified differently. Baroreflex slopes (%/mmHg) for some medium APs (cluster 5: -4.4 ± 4 to -9.1 ± 5) expressed the greatest increase with LBNP, while slopes for large APs (cluster 9: -1.3 ± 1 to -2.6 ± 2) also increased, but to a lesser degree. Slopes for small APs present at BSL exhibited reductions with LBNP (cluster 2: -3.9 ± 3 to -2.2 ± 3). Larger previously silent AP clusters recruited with LBNP expressed weak baroreflex regulation (cluster 14: -0.9 ± 1%/mmHg). The baroreflex exerts the strongest control over medium-sized APs. Augmenting baroreflex gain and upward resetting of discrete AP subpopulations active at BSL, as well as recruiting larger previously silent APs with weak baroreflex control, facilitates elevated MSNA during orthostatic stress.
Assuntos
Barorreflexo , Músculo Esquelético , Potenciais de Ação , Pressão Sanguínea , Frequência Cardíaca , Humanos , Pressão Negativa da Região Corporal Inferior , Sistema Nervoso SimpáticoRESUMO
What strategies are employed by the sympathetic system to communicate with the circulation? Muscle sympathetic nerve activity (MSNA) occurs in bursts of synchronous action potential (AP) discharge, yet whether between-burst asynchronous AP firing exists remains unknown. Using multiunit microneurography and a continuous wavelet transform to isolate APs, we studied AP synchronicity within human MSNA. Asynchronous APs were defined as those which occurred between bursts. Experiment 1 quantified AP synchronicity in eight individuals at baseline (BSL), -10 mmHg lower body negative pressure (LBNP), -40 mmHg LBNP, and end-expiratory apnea (APN). At BSL, 33 ± 12% of total AP activity was asynchronous. Asynchronous discharge was unchanged from BSL (67 ± 37 AP/min) to -10 mmHg LBNP (69 ± 33 AP/min), -40 mmHg LBNP (83 ± 68 AP/min), or APN (62 ± 39 AP/min). Across all conditions, asynchronous AP probability and frequency decreased with increasing AP size. Experiment 2 examined the impact of the ganglia on AP synchronicity by using nicotinic blockade (trimethaphan). The largest asynchronous APs were derecruited from BSL (11 ± 4 asynchronous AP clusters) to the last minute of the trimethaphan infusion with visible bursts (7 ± 2 asynchronous AP clusters). However, the 6 ± 2 smallest asynchronous AP clusters could not be blocked by trimethaphan and persisted to fire 100 ± 0% asynchronously without forming bursts. Nonnicotinic ganglionic mechanisms affect some, but not all, asynchronous activity. The fundamental behavior of human MSNA contains between-burst asynchronous AP discharge, which accounts for a considerable amount of BSL activity.NEW & NOTEWORTHY Historically, sympathetic nerve activity destined for the blood vessels supplying skeletal muscle (MSNA) has been characterized by spontaneous bursts formed by synchronous action potential (AP) discharge. However, this study found a considerable amount (~30% during baseline) of sympathetic AP discharge to fire asynchronously between bursts of human MSNA. Trimethaphan infusion revealed that nonnicotinic ganglionic mechanisms contribute to some, but not all, asynchronous discharge. Asynchronous sympathetic AP discharge represents a fundamental behavior of MSNA.
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Potenciais de Ação , Vasos Sanguíneos/inervação , Músculo Esquelético/irrigação sanguínea , Sistema Nervoso Simpático/fisiologia , Potenciais de Ação/efeitos dos fármacos , Adulto , Apneia/fisiopatologia , Barorreflexo , Feminino , Bloqueadores Ganglionares/farmacologia , Humanos , Pressão Negativa da Região Corporal Inferior , Masculino , Antagonistas Nicotínicos/farmacologia , Sistema Nervoso Simpático/efeitos dos fármacos , Fatores de Tempo , Trimetafano/farmacologia , Adulto JovemAssuntos
Acoplamento Neurovascular , Óxido Nítrico , Encéfalo , Circulação Cerebrovascular , HumanosRESUMO
The aim of this study was to determine the effect of posture changes on vascular compliance in intracranial (brain) versus extracranial vascular beds (forearm). Eighteen young adults (nine females) performed a supine-to-seated-to-standing protocol involving 5 min of rest in each position. Continuous blood pressure, middle cerebral artery (MCA) blood velocity, and brachial artery blood velocity were recorded at each posture. Three to five consecutive steady-state cardiac cycles at each posture were analyzed by a four-element lumped parameter modified Windkessel model to calculate vascular compliance. Mean arterial pressure (MAP) increased from supine to seated (76(9) vs. 81(12) mmHg; P = 0.006) and from supine to standing (76(9) vs. 82(13) mmHg; P = 0.034). Mean blood flow was greater in the MCA relative to the forearm (forearm: 40(5) mL·min-1, MCA: 224(17) mL·min-1; main effect P < 0.001). Conversely, vascular resistance (forearm: 3.25(0.50) mmHg-1·mL·min-1, brain: 0.36(0.04) mmHg-1·mL·min-1; main effect P < 0.001) and compliance (forearm: 0.010(0.001) mL·min-1·mmHg-1, brain: 0.005(0.001) mL·min-1·mmHg-1; main effect P = 0.001) were greater in the forearm compared to the brain. Significant main effects of posture were observed with decreasing values in upright positions for mean blood flow (P = 0.001) in both vascular beds, but not for resistance (P = 0.163) or compliance (P = 0.385). There were no significant interaction effects between vascular bed and posture for mean flow (P = 0.057), resistance (P = 0.258), or compliance (P = 0.329). This study provides evidence that under steady-state conditions, posture does not affect cerebrovascular compliance.
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Circulação Cerebrovascular , Artéria Cerebral Média , Postura , Resistência Vascular , Humanos , Feminino , Masculino , Circulação Cerebrovascular/fisiologia , Adulto Jovem , Postura/fisiologia , Artéria Cerebral Média/fisiologia , Adulto , Resistência Vascular/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Braquial/fisiologia , Antebraço/irrigação sanguínea , Postura Sentada , Decúbito Dorsal/fisiologia , Pressão Sanguínea/fisiologia , Complacência (Medida de Distensibilidade) , Posição Ortostática , Pressão ArterialRESUMO
Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.
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Characterization of dynamic cerebral autoregulation has focused primarily on adjustments in cerebrovascular resistance in response to blood pressure (BP) alterations. However, the role of vascular compliance in dynamic autoregulatory processes remains elusive. The present study examined changes in cerebrovascular compliance and resistance during standing-induced transient BP reductions in nine young, healthy adults (3 women). Brachial artery BP (Finometer) and middle cerebral artery blood velocity (BV; Multigon) waveforms were collected. Beginning 20 beats before standing and continuing 40 beats after standing, individual BP and BV waveforms of every second heartbeat were extracted and input into a four-element modified Windkessel model to calculate indexes of cerebrovascular resistance (Ri) and compliance (Ci). Standing elicited a transient reduction in mean BP of 20 ± 9 mmHg. In all participants, a large increase in Ci (165 ± 84%; P < 0.001 vs. seated baseline) occurred 2 ± 2 beats following standing. Reductions in Ri occurred 11 ± 3 beats after standing (Ci vs. Ri delay: P < 0.001). The increase in Ci contributed to maintained systolic BV before the decrease in Ri. The present results demonstrate rapid, large but transient increases in Ci that precede reductions in Ri, in response to standing-induced reductions in BP. Therefore, Ci represents a discreet component of cerebrovascular responses during acute decreases in BP and, consequently, dynamic autoregulation.NEW & NOTEWORTHY Historically, dynamic cerebral autoregulation has been characterized by adjustments in cerebrovascular resistance following systematic changes in blood pressure. However, with the use of Windkessel modeling approaches, this study revealed rapid and large increases in cerebrovascular compliance that preceded reductions in cerebrovascular resistance following standing-induced blood pressure reductions. Importantly, the rapid cerebrovascular compliance response contributed to preservation of systolic blood velocity during the transient hypotensive phase. These results broaden our understanding of dynamic cerebral autoregulation.
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Circulação Cerebrovascular , Ultrassonografia Doppler Transcraniana , Adulto , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Feminino , Humanos , Artéria Cerebral Média/diagnóstico por imagemRESUMO
Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls (P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls (P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls (P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.
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Encéfalo/fisiologia , Mergulho/fisiologia , Homeostase/fisiologia , Adulto , Apneia/metabolismo , Apneia/fisiopatologia , Velocidade do Fluxo Sanguíneo/fisiologia , Pressão Sanguínea/fisiologia , Encéfalo/metabolismo , Suspensão da Respiração , Dióxido de Carbono/metabolismo , Circulação Cerebrovascular/fisiologia , Eletrocardiografia/métodos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipercapnia/metabolismo , Hipercapnia/fisiopatologia , Hipóxia/metabolismo , Hipóxia/fisiopatologia , Masculino , Artéria Cerebral Média/metabolismo , Artéria Cerebral Média/fisiologia , Ultrassonografia Doppler Transcraniana/métodos , Vasodilatação/fisiologiaRESUMO
Pulsatile blood flow is generally mediated by the compliance of blood vessels whereby they distend locally and momentarily to accommodate the passage of the pressure wave. This freedom of the blood vessels to exercise their compliance may be suppressed within the confines of the rigid skull. The effect of this on the mechanics of pulsatile blood flow within the cerebral circulation is not known, and the situation is compounded by experimental access difficulties. We present an approach which we have developed to overcome these difficulties in a study of the mechanics of pulsatile cerebral blood flow. The main finding is that while the innate compliance of cerebral vessels is indeed suppressed within the confines of the skull, this is compensated somewhat by compliance provided by other "extravascular" elements within the skull. The net result is what we have termed "intracranial compliance," which we argue is more pertinent to the mechanics of pulsatile cerebral blood flow than is intracranial pressure.
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PURPOSE: Although cerebrovascular impairments are believed to contribute to concussion symptoms, little information exists regarding brain vasomotor control in adolescent concussion, particularly autoregulatory control that forms a fundamental response mechanism during changes in blood pressure. This research tested the hypothesis that adolescent concussion is marked by impaired dynamic cerebral autoregulation. METHODS: Nineteen concussed adolescents (15 ± 2 yr, 13 females) and 18 healthy controls (15 ± 2 yr, 9 females) completed two sit-to-stand trials. Brachial artery blood pressure and cerebral blood flow velocity in the right middle cerebral artery were measured continuously. Dynamic rate of regulation was calculated as the rate of change in cerebrovascular resistance relative to the change in arterial blood pressure. The concussed adolescents were followed through their rehabilitation for up to 12 wk. RESULTS: At the first visit, the concussed adolescents demonstrated reduced rate of regulation compared with the healthy controls (0.12 ± 0.04 vs 0.19 ± 0.06 s, P ≤ 0.001). At the concussed adolescents final visit, after symptom resolution, the rate of regulation improved to levels that were not different from the healthy controls (n = 9; 0.15 ± 0.08 vs 0.19 ± 0.06 s, P= 0.06). Two distinct groups were observed at the final visit with some individuals experiencing recovery of dynamic cerebral autoregulation and others showing no marked change from the initial visit. CONCLUSION: Adolescents demonstrate an impairment in dynamic cerebral autoregulation after concussion that improves along with clinical symptoms in some individuals and remains impaired in others despite symptom resolution.