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Cerebrovascular and neurological diseases exhibit sex-specific patterns in prevalence, severity, and regional specificity, some of which are associated with altered cerebral blood flow (CBF). Females often exhibit higher resting CBF, but understanding the impact of sex per se on CBF is hampered by study variability in age, comorbidities, medications, and control for menstrual cycle or hormone therapies. A majority of studies report whole brain CBF without differentiating between grey and white matter, or without assessing regional CBF. Thus, fundamental sex differences in regional or whole-brain CBF remain unclarified. While controlling for the above confounders, we tested the hypothesis that females will exhibit higher total grey and white matter perfusion as well as regional grey matter perfusion. Adults 18-30 years old (females=22, males=26), were studied using arterial spin labeling (ASL) magnetic resonance imaging (MRI) scans followed by Computational Anatomy Toolbox (CAT12) analysis in Statistical Parametric Mapping (SPM12) to quantify CBF relative to brain volume. Females displayed 40% higher perfusion globally (females =62±9, males=45±10mL/100g/min, p<0.001), grey matter (females=75±11, males=54±12mL/100g/min, p<0.001), and white matter (females=44±6, males=32±7mL/100g/min, p<0.001). Females exhibited greater perfusion than males in 67 of the 68 regions tested, ranging from 14-66% higher. A second MRI approach (4D flow) focused on large arteries confirmed the sex difference in global CBF. These data indicate strikingly higher basal CBF in females at global, grey, and white matter levels and across dozens of brain regions, and offer new clarity into fundamental sex differences in global and regional CBF regulation prior to aging or pathology.
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Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Methods: Nineteen juvenile female swine were included in the study. ARDS defined by a PaO2/FiO2 ratio < 300 was induced by continuous oleic acid infusion. Arterial blood was drawn before and during oleic acid infusion, and when ARDS was established. Cytokine expression in WBC was analyzed by RT-qPCR and plasma protein expression by ELISA. Results: The median concentration of IFN-γ mRNA was estimated to be 59% (p = 0.006) and of IL-6 to be 44.4% (p = 0.003) of the baseline amount. No significant changes were detected for TNF-α, IL-17, and IL-10 mRNA expression. In contrast, the concentrations of plasma IFN-γ and IL-6 were significantly higher (p = 0.004 and p = 0.048 resp.), and TNF-α was significantly lower (p = 0.006) at ARDS compared to baseline. Conclusions: The change of proinflammatory cytokines IFN-γ and IL-6 expression is different comparing mRNA and plasma proteins at oleic acid-induced ARDS compared to baseline. The migration of cells to the lung may be the cause for this discrepancy.
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Lesão Pulmonar Aguda , Síndrome do Desconforto Respiratório , Humanos , Feminino , Animais , Suínos , Ácido Oleico , Fator de Necrose Tumoral alfa , Interleucina-6 , Citocinas , Lesão Pulmonar Aguda/induzido quimicamente , Síndrome do Desconforto Respiratório/induzido quimicamenteRESUMO
PURPOSE: To investigate the correlation between volume of carbon dioxide elimination (VÌCO2) and end-tidal carbon dioxide (PETCO2) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model. METHODS: Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion. RESULTS: Prior to ARDS induction, mean (SD) CO, VÌCO2, PETCO2, and dead space to tidal volume ratio (Vd/Vt) were 4.16 (1.10) L/min, 103.69 (18.06) ml/min, 40.72 (3.88) mmHg and 0.25 (0.09) respectively. Partial correlation coefficients between average CO, VÌCO2, and PETCO2 were 0.44 (95% confidence interval: 0.18-0.69) and 0.50 (0.18-0.74), respectively. After ARDS induction, mean CO, VÌCO2, PETCO2, and Vd/Vt were 3.33 (0.97) L/min, 113.71 (22.97) ml/min, 50.17 (9.73) mmHg and 0.40 (0.08). Partial correlations between CO and VÌCO2 was 0.01 (-0.31 to 0.37) and between CO and PETCO2 was 0.35 (-0.002 to 0.65). CONCLUSION: ARDS may limit the utility of volumetric capnography to monitor CO.
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Dióxido de Carbono , Síndrome do Desconforto Respiratório , Humanos , Criança , Animais , Suínos , Volume de Ventilação Pulmonar , Débito Cardíaco , Capnografia , Respiração ArtificialRESUMO
Introduction: Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund "Spanish flu pandemic" patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been completely displaced by 100% oxygen to create the modern pharmaceutical hyperbaric oxygen therapy (HBOT), a powerful treatment that is FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count. Methods: Ten 34-35-year-old healthy volunteers were exposed to 1.27ATA (4 psig/965 mmHg) room air for 90 min, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: (1) prior to the first exposure (served as the control for each subject), (2) directly after the first exposure (to measure the acute effect), (3) immediately prior to the ninth exposure (to measure the chronic effect), and (4) 3 days after the completion of tenth/final exposure (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry. Results: SPCs (CD45dim/CD34+/CD133-) were mobilized by nearly two-fold following 9 exposures (p = 0.02) increasing to three-fold 72-h post completion of the final (10th) exposure (p = 0.008) confirming durability. Discussion: This research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated to reflect a dose treatment finding rather than finding a placebo effect. Our findings of SPC mobilization by HBA support further investigation into hyperbaric air as a pharmaceutical/therapy.
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NEW FINDINGS: What is the central question of this study? What is the relationship between prostacyclin and cerebrovascular reactivity to hypercapnia before and after administration of a cyclooxygenase inhibitor, indomethacin, in healthy young and older adults? What is the main finding and importance? Serum prostacyclin was not related to cerebrovascular reactivity to hypercapnia before or after administration of indomethacin. However, in older adults, serum prostacyclin was related to the magnitude of change in cerebrovascular reactivity from before to after indomethacin administration. This suggests that older adults with higher serum prostacyclin may rely more on cyclooxygenase products to mediate cerebrovascular reactivity. ABSTRACT: Platelet activation may contribute to age-related cerebrovascular dysfunction by interacting with the endothelial cells that regulate the response to vasodilatory stimuli. This study evaluated the relationship between a platelet inhibitor, prostacyclin, and cerebrovascular reactivity (CVR) in healthy young (n = 35; 25 ± 4 years; 17 women, 18 men) and older (n = 12; 62 ± 2 years; 8 women, 4 men) adults, who were not daily aspirin users, before and after cyclooxygenase inhibition. Prostacyclin was determined by levels of 6-keto-prostaglandin F1α (6-keto PGF1α) in the blood. CVR was assessed by measuring the middle cerebral artery blood velocity response to hypercapnia using transcranial Doppler ultrasound before (CON) and 90 min after cyclooxygenase inhibition with indomethacin (INDO). In young adults, there were no associations between prostacyclin and middle cerebral artery CVR during CON (r = -0.14, P = 0.415) or INDO (r = 0.27, P = 0.118). In older adults, associations between prostacyclin and middle cerebral artery CVR during CON (r = 0.53, P = 0.075) or INDO (r = -0.45, P = 0.136) did not reach the threshold for significance. We also evaluated the relationship between prostacyclin and the change in CVR between conditions (ΔCVR). We found no association between ΔCVR and prostacyclin in young adults (r = 0.27, P = 0.110); however, in older adults, those with higher baseline prostacyclin levels demonstrated significantly greater ΔCVR (r = -0.74, P = 0.005). In conclusion, older adults with higher serum prostacyclin, a platelet inhibitor, may rely more on cyclooxygenase products for cerebrovascular reactivity to hypercapnia.
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Epoprostenol , Hipercapnia , Masculino , Adulto Jovem , Humanos , Feminino , Idoso , Epoprostenol/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Prostaglandina-Endoperóxido Sintases , Células Endoteliais , Indometacina/farmacologia , Prostaglandinas I/farmacologia , Circulação Cerebrovascular/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Dióxido de CarbonoRESUMO
Ninety-million Americans suffer metabolic syndrome (MetSyn), increasing the risk of diabetes and poor brain outcomes, including neuropathology linked to lower cerebral blood flow (CBF), predominantly in anterior regions. We tested the hypothesis that total and regional CBF is lower in MetSyn more so in the anterior brain and explored three potential mechanisms. Thirty-four controls (25 ± 5 yr) and 19 MetSyn (30 ± 9 yr), with no history of cardiovascular disease/medications, underwent four-dimensional flow magnetic resonance imaging (MRI) to quantify macrovascular CBF, whereas arterial spin labeling quantified brain perfusion in a subset (n = 38/53). Contributions of cyclooxygenase (COX; n = 14), nitric oxide synthase (NOS, n = 17), or endothelin receptor A signaling (n = 13) were tested with indomethacin, NG-monomethyl-L-arginine (L-NMMA), and Ambrisentan, respectively. Total CBF was 20 ± 16% lower in MetSyn (725 ± 116 vs. 582 ± 119 mL/min, P < 0.001). Anterior and posterior brain regions were 17 ± 18% and 30 ± 24% lower in MetSyn; reductions were not different between regions (P = 0.112). Global perfusion was 16 ± 14% lower in MetSyn (44 ± 7 vs. 36 ± 5 mL/100 g/min, P = 0.002) and regionally in frontal, occipital, parietal, and temporal lobes (range 15-22%). The decrease in CBF with L-NMMA (P = 0.004) was not different between groups (P = 0.244, n = 14, 3), and Ambrisentan had no effect on either group (P = 0.165, n = 9, 4). Interestingly, indomethacin reduced CBF more in Controls in the anterior brain (P = 0.041), but CBF decrease in posterior was not different between groups (P = 0.151, n = 8, 6). These data indicate that adults with MetSyn exhibit substantially reduced brain perfusion without regional differences. Moreover, this reduction is not due to loss of NOS or gain of ET-1 signaling but rather a loss of COX vasodilation.NEW & NOTEWORTHY We tested the impact of insulin resistance (IR) on resting cerebral blood flow (CBF) in adults with metabolic syndrome (MetSyn). Using MRI and research pharmaceuticals to study the role of NOS, ET-1, or COX signaling, we found that adults with MetSyn exhibit substantially lower CBF that is not explained by changes in NOS or ET-1 signaling. Interestingly, adults with MetSyn show a loss of COX-mediated vasodilation in the anterior but not posterior circulation.
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Síndrome Metabólica , Humanos , Adulto Jovem , ômega-N-Metilarginina , Indometacina , Circulação Cerebrovascular/fisiologiaRESUMO
Purpose: To measure native T1 values, a marker of diffuse fibrosis, by using cardiac MRI (CMR) in young adults born prematurely. Materials and Methods: This secondary analysis of a prospective cohort study included young adults born moderately to extremely preterm and age-matched, term-born participants. CMR was performed with a 3.0-T imager that included cine imaging for the quantification of left ventricular (LV) and right ventricular (RV) volumes and function and native saturation recovery T1 mapping for the assessment of diffuse myocardial fibrosis. Values between preterm and term were compared by using the Student t test. Associations between T1 values and other variables were analyzed by using linear regression and multivariate regression. Results: Of the 50 young-adult participants, 32 were born preterm (mean age, 25.8 years ± 4.2 [SD]; 23 women) and 18 were born at term (mean age, 26.2 years ± 5.4; 10 women). Native T1 values were significantly higher in participants born preterm than in participants born at term (1477 msec ± 77 vs 1423 msec ± 71, respectively; unadjusted P = .0019). Native T1 values appeared to be positively associated with indexed LV end-diastolic and end-systolic volumes (ß = 2.1, standard error = 0.7 and ß = 3.8, standard error = 1.2, respectively), the RV end-diastolic volume index (ß = 1.3, standard error = 0.6), and the LV mass index (ß = 2.5, standard error = 0.9). Higher T1 values may be associated with reduced cardiac systolic strain measures and diastolic strain measures. Five-minute Apgar scores were inversely associated with native T1 values. Conclusion: Young adults born moderately to extremely preterm exhibited significantly higher native T1 values than age-matched, term-born young adults.Keywords: MRI, Cardiac, Heart, Left Ventricle, CardiomyopathiesClinical trial registration no. NCT03245723Published under a CC BY 4.0 license Supplemental material is available for this article.
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Central adiposity is associated with greater sympathetic support of blood pressure. ß-adrenergic receptors (ß-AR) buffer sympathetically mediated vasoconstriction and ß-AR-mediated vasodilation is attenuated in preclinical models of obesity. With this information, we hypothesized ß-AR vasodilation would be lower in obese compared with normal weight adults. Because ß-AR vasodilation in normal weight adults is limited by cyclooxygenase (COX) restraint of nitric oxide synthase (NOS), we further explored the contributions of COX and NOS to ß-AR vasodilation in this cohort. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured and forearm vascular conductance (FVC) was calculated (FVC = FBF/MAP). The rise in FVC from baseline (ΔFVC) was quantified during graded brachial artery infusion of isoproterenol (Iso, 1-12 ng/100 g/min) in normal weight (n = 36) and adults with obesity (n = 22) (18-40 yr old). In a subset of participants, Iso-mediated vasodilation was examined before and during inhibition of NOS [NG-monomethyl-l-arginine (l-NMMA)], COX (ketorolac), and NOS + COX (l-NMMA + ketorolac). Iso-mediated increases in FVC did not differ between groups (P = 0.57). l-NMMA attenuated Iso-mediated ΔFVC in normal weight (P = 0.03) but not adults with obesity (P = 0.27). In normal weight adults, ketorolac increased Iso-mediated ΔFVC (P < 0.01) and this response was lost with concurrent l-NMMA (P = 0.67). In contrast, neither ketorolac (P = 0.81) nor ketorolac + l-NMMA (P = 0.40) altered Iso-mediated ΔFVC in adults with obesity. Despite shifts in COX and NOS, ß-AR vasodilation is preserved in young adults with obesity. These data highlight the presence of a compensatory shift in microvascular control mechanisms in younger humans with obesity.NEW & NOTEWORTHY We examined ß-adrenergic receptor-mediated vasodilation in skeletal muscle of humans with obesity and normal weight. Results show that despite shifts in the contribution of cyclooxygenase and nitric oxide synthase, ß-adrenergic-mediated vasodilation is relatively preserved in young, otherwise healthy adults with obesity. These data highlight the presence of subclinical changes in microvascular control mechanisms early in the obesity process and suggest duration of obesity and/or the addition of primary aging may be necessary for overt dysfunction.
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Músculo Esquelético/irrigação sanguínea , Óxido Nítrico Sintase Tipo III/metabolismo , Obesidade/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Vasodilatação , Agonistas Adrenérgicos beta/farmacologia , Adulto , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiologia , Inibidores de Ciclo-Oxigenase/farmacologia , Feminino , Humanos , Isoproterenol/farmacologia , Cetorolaco/farmacologia , Masculino , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Obesidade/fisiopatologia , Receptores Adrenérgicos beta/metabolismo , ômega-N-Metilarginina/farmacologiaRESUMO
BACKGROUND: Preterm birth has been linked to an elevated risk of heart failure and cardiopulmonary disease later in life. With improved neonatal care and survival, most infants born preterm are now reaching adulthood. In this study, we used 4D flow cardiovascular magnetic resonance (CMR) coupled with an exercise challenge to assess the impact of preterm birth on right heart flow dynamics in otherwise healthy adolescents and young adults who were born preterm. METHODS: Eleven young adults and 17 adolescents born preterm (< 32 weeks of gestation and < 1500 g birth weight) were compared to 11 young adult and 18 adolescent age-matched controls born at term. Stroke volume, cardiac output, and flow in the main pulmonary artery were quantified with 4D flow CMR. Kinetic energy and vorticity were measured in the right ventricle. All parameters were measured at rest and during exercise at a power corresponding to 70% VO2max for each subject. Multivariate linear regression was used to perform age-adjusted term-preterm comparisons. RESULTS: With exercise, stroke volume increased 10 ± 21% in term controls and decreased 4 ± 18% in preterm born subjects (p = 0.007). This resulted in significantly reduced capacity to increase cardiac output in response to exercise stress for the preterm group (58 ± 26% increase in controls, 36 ± 27% increase in preterm, p = 0.004). Elevated kinetic energy (KEterm = 71 ± 22 nJ, KEpreterm = 87 ± 38 nJ, p = 0.03) and vorticity (ωterm = 79 ± 16 s-1, ωpreterm = 94 ± 32 s-1, p = 0.01) during diastole in the right ventricle (RV) suggested altered RV flow dynamics in the preterm subjects. Streamline visualizations showed altered structure to the diastolic filling vortices in those born preterm. CONCLUSIONS: For the participants examined here, preterm birth appeared to result in altered right-heart flow dynamics as early as adolescence, especially during diastole. Future studies should evaluate whether the altered dynamics identified here evolves into cardiopulmonary disease later in life. Trial registration None.
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Nascimento Prematuro , Adolescente , Adulto , Teste de Esforço , Feminino , Ventrículos do Coração , Humanos , Recém-Nascido , Valor Preditivo dos Testes , Gravidez , Volume Sistólico , Adulto JovemRESUMO
The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack a comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region-specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. Fourteen healthy adults (7 females; 24 ± 5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L-NMMA, administered in a randomized, single-blind approach. 4D flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labelling (ASL) MRI quantified total and regional microvascular perfusion. L-NMMA (or volume-matched saline) was infused intravenously for 5 min prior to imaging. L-NMMA reduced CBF (L-NMMA: 722 ± 100 vs. placebo: 771 ± 121 ml/min, P = 0.01) with similar relative reductions (5-7%) in anterior and posterior cerebral circulations, due in part to the reduced cross-sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L-NMMA (L-NMMA: 42 ± 7 vs. placebo: 47 ± 8 ml/100g/min, P = 0.02), with 7-11% reductions in both hemispheres of the frontal, parietal and temporal lobes, and in the left occipital lobe. We conclude that NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. KEY POINTS: Cerebral blood flow (CBF) is vital for brain health, but the signals that are key to regulating CBF remain unclear. Nitric oxide (NO) is produced in the brain, but its importance in regulating CBF remains controversial since prior studies have not studied all regions of the brain simultaneously. Using modern MRI approaches, a drug that inhibits the enzymes that make NO (L-NMMA) reduced CBF by up to 11% in different brain regions. NO helps maintain proper CBF in healthy adults. These data will help us understand whether the reductions in CBF that occur during ageing or cardiovascular disease are related to shifts in NO signalling.
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Circulação Cerebrovascular , Óxido Nítrico Sintase , Fluxo Sanguíneo Regional , ômega-N-Metilarginina , Adulto , Feminino , Humanos , Masculino , Óxido Nítrico , Óxido Nítrico Sintase/antagonistas & inibidores , Perfusão , Método Simples-Cego , Adulto Jovem , ômega-N-Metilarginina/farmacologiaRESUMO
PURPOSE: To use four-dimensional (4D) flow MRI to measure intraventricular flow in young adults who were born prematurely to investigate mechanisms that may account for increased heart failure risk in this population. MATERIALS AND METHODS: In this secondary analysis of a prospective study, a total of 56 young adults participated in an observational cardiac 4D flow MRI study from 2016 to 2020. There were 35 participants who had been born moderately to extremely prematurely (birth weight <1500 g or gestational age ≤32 weeks; 23 women; mean age, 26 years ± 4) and 21 term-born participants (11 women; mean age, 25 years ± 3). Participants underwent cardiac MRI, including cine cardiac structure and function assessment, as well as 4D flow MRI. In each ventricle, normalized kinetic energy (KE/end diastolic volume) and flow through the atrioventricular valve were computed and compared between term-born and preterm participants at systolic and diastolic (early diastolic filling rate [E wave] and late diastolic filling [atrial contraction] rate [A wave]) time points by using Wilcoxon rank-sum tests. RESULTS: Preterm-born participants had lower right ventricular (RV) E wave/A wave (E/A) KE ratios (2.4 ± 1.7 vs 3.5 ± 1.4; P <.01) and lower E/A peak filling rate ratios (computed from RV volume-time curves; 2.3 ± 1.3 vs 3.5 ± 2.5; P = .03). Additionally, viscous energy dissipation was increased during systole (5.7 µW/mL ± 3.0 vs 4.2 µW/mL ± 1.6; P = .03), increased during late diastole (3.9 µW/mL ± 4.0 vs 2.2 µW/mL ± 1.6; P = .03), and summed over the cardiac cycle (2.4 µJ/mL ± 1.0 vs 1.9 µJ/mL ± 0.6; P = .02) in preterm relative to term participants. CONCLUSION: These results suggest that RV diastolic filling is altered in young adults who were born moderately to severely prematurely.Supplemental material is available for this article. Keywords: Adults, Cardiac, Comparative Studies, MR-Imaging, Right Ventricle © RSNA, 2021.
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BACKGROUND: Premature birth is associated with lower levels of cardiorespiratory fitness (CRF) but the underlying mechanisms responsible remain unclear. This study assessed whether differences in cardiac morphology or function mediate differences in CRF among adolescents and young adults born preterm. METHODS: Adolescents and young adults born moderately to extremely premature (gestational ageâ¯≤â¯32â¯weeks or birth weightâ¯<â¯1500â¯g) and age-matched term born participants underwent resting cardiac MRI and maximal exercise testing. Mediation analysis assessed whether individual cardiovascular variables accounted for a significant proportion of the difference in maximal aerobic capacity between groups. RESULTS: Individuals born preterm had lower VO2max than those born term (41.7⯱â¯8.6 v 47.5⯱â¯8.7, pâ¯<â¯0.01). Several variables differed between term and preterm born subjects, including systolic and diastolic blood pressure, mean pulmonary artery pressure, indexed left ventricular end-diastolic volume (LVEDVi), right ventricular end-diastolic volume (RVEDVi), LV mass (LVMi), LV stroke volume index (LVSVi), and LV strain (pâ¯<â¯0.05 for all). Of these variables, LVEDVi, RVEDVi, LVSVi, LVMi, and LV longitudinal strain were significantly related to VO2max (pâ¯<â¯0.05 for all). Significant portions of the difference in VO2max between term and preterm born subjects were mediated by LVEDVi (74.3%, pâ¯=â¯0.010), RVEDVi (50.6%, pâ¯=â¯0.016), and LVMi (43.0%, pâ¯=â¯0.036). CONCLUSIONS: Lower levels of CRF in adolescents and young adults born preterm are mediated by differences in LVEDVi, RVEDVi, and LVMi. This may represent greater risk for long-term cardiac morbidity and mortality in preterm born individuals.
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Nascimento Prematuro , Adolescente , Tolerância ao Exercício , Feminino , Coração , Ventrículos do Coração/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Gravidez , Volume Sistólico , Adulto JovemRESUMO
Structural and functional changes in the cerebral vasculature occur with advancing age, which may lead to impaired neurovascular coupling (NVC) and cognitive decline. Cyclooxygenase (COX) inhibition abolishes age-related differences in cerebrovascular reactivity, but it is unclear if COX inhibition impacts NVC. The purpose of this study was to examine the influence of aging on NVC before and after COX inhibition. Twenty-three young (age = 25 ± 4 yr) and 21 older (age = 64 ± 5 yr) adults completed two levels of difficulty of the Stroop and n-back tests before and after COX inhibition. Middle cerebral artery blood velocity (MCAv) was measured using transcranial Doppler ultrasound and mean arterial blood pressure (MAP) was measured using a finger cuff. Hemodynamic variables were measured at rest and in response to cognitive challenges. During the Stroop test, older adults demonstrated a greater increase in MCAv (young: 2.2 ± 6.8% vs. older: 5.9 ± 5.8%; P = 0.030) and MAP (young: 2.0 ± 4.9% vs. older: 4.8 ± 4.9%; P = 0.036) compared with young adults. There were no age-related differences during the n-back test. COX inhibition reduced MCAv by 30% in young and 26% in older adults (P < 0.001 for both). During COX inhibition, there were no age-related differences in the percent change in MCAv or MAP in response to the cognitive tests. Our results show that older adults require greater increases in MCAv and MAP during a test of executive function compared with young adults and that any age-related differences in NVC were abolished during COX inhibition. Collectively, this suggests that aging is associated with greater NVC necessary to accomplish a cognitive task.
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Circulação Cerebrovascular/efeitos dos fármacos , Cognição , Envelhecimento Cognitivo/psicologia , Inibidores de Ciclo-Oxigenase/farmacologia , Hemodinâmica/efeitos dos fármacos , Indometacina/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Acoplamento Neurovascular/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Idoso , Função Executiva , Feminino , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Teste de Stroop , Fatores de Tempo , Adulto JovemRESUMO
Individuals born prematurely have smaller hearts, cardiac limitations to exercise, and increased overall cardiometabolic risk. The cardiac effects of acute hypoxia exposure as another physiologic stressor remain under explored. The purpose of this study was to determine the effects of hypoxia on ventricular function in adults born preterm. Adults born moderately to extremely preterm (≤32 weeks gestation or <1500 g, N = 32) and born at term (N = 18) underwent cardiac magnetic resonance imaging under normoxic (21% O2) and hypoxic (12% O2) conditions to assess cardiovascular function. In normoxia, cardiac function parameters were similar between groups. During hypoxia, the right ventricular (RV) contractile response was significantly greater in participants born premature, demonstrated by greater increases in RV ejection fraction (EF) (p = 0.002), ventricular-vascular coupling (VVC) (p = 0.004), and strain (p < 0.0001) measures compared to term-born participants, respectively. Left ventricular contractile reserve was similar to term-born participants. Adults born preterm exhibit an exaggerated contractile response to acute hypoxia, particularly in the RV. This suggests that adults born preterm may have contractile reserve, despite the lack of volume reserve identified in previous exercise studies. However, this exaggerated and hyper-adapted response may also increase their risk for late RV failure.
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The aim of this study was to examine the use of volumetric capnography monitoring to assess cardiopulmonary resuscitation (CPR) effectiveness by correlating it with cardiac output (CO), and to evaluate the effect of epinephrine boluses on both end-tidal carbon dioxide (EtCO 2 ) and the volume of CO 2 elimination (VCO 2 ) in a swine ventricular fibrillation cardiac arrest model. Planned secondary analysis of data collected to investigate the use of noninvasive monitors in a pediatric swine ventricular fibrillation cardiac arrest model was performed. Twenty-eight ventricular fibrillatory arrests with open cardiac massage were conducted. During CPR, EtCO 2 and VCO 2 had strong correlation with CO, measured as a percentage of baseline pulmonary blood flow, with correlation coefficients of 0.83 ( p < 0.001) and 0.53 ( p = 0.018), respectively. However, both EtCO 2 and VCO 2 had weak and nonsignificant correlation with diastolic blood pressure during CPR 0.30 ( p = 0.484) (95% confidence interval [CI], -0.51-0.83) and 0.25 ( p = 0.566) (95% CI, -0.55-0.81), respectively. EtCO 2 and VCO 2 increased significantly after the first epinephrine bolus without significant change in CO. The correlations between EtCO 2 and VCO 2 and CO were weak 0.20 ( p = 0.646) (95% CI, -0.59-0.79), and 0.27 ( p = 0.543) (95% CI, -0.54-0.82) following epinephrine boluses. Continuous EtCO 2 and VCO 2 monitoring are potentially useful metrics to ensure effective CPR. However, transient epinephrine administration by boluses might confound the use of EtCO 2 and VCO 2 to guide chest compression.
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PURPOSE: To explore the feasibility of using four-dimensional (4D) flow MRI to quantify blood flow and kinetic energy (KE) in the heart during strenuous exercise. MATERIALS AND METHODS: For this prospective study, cardiac 4D flow MRI was performed in 11 healthy young adult participants (eight men, three women; mean age, 26 years ± 1 [standard deviation]) at rest and during exercise with an MRI-compatible exercise stepper between March 2016 and July 2017. Flow was measured in the ascending aorta (AAo) and main pulmonary artery (MPA). KE was quantified in the left and right ventricle. Significant changes in flow and KE during exercise were identified by using t tests. Repeatability was assessed with inter- and intraobserver comparisons and an analysis of internal flow consistency. RESULTS: Nine participants successfully completed both rest and exercise imaging. Internal flow consistency analysis in systemic and pulmonary circulation showed average relative differences of 10% at rest and 16% during exercise. For flow measurements in the AAo and MPA, relative differences between observers never exceeded 6% in any vessel and showed excellent correlation, even during exercise. Relative differences were increased for KE, typically on the order of 30%, with poor interobserver correlation between measurements. CONCLUSION: Four-dimensional flow MRI can quantify increases in flow in the AAo and MPA during strenuous exercise and is highly repeatable. KE had reduced repeatability because of suboptimal segmentation methods and requires further development before clinical implementation. Supplemental material is available for this article. © RSNA, 2020See also the commentary by Markl and Lee in this issue.
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Recém-Nascido Prematuro , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Microvasos/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto , Meios de Contraste , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Sobreviventes , Adulto JovemRESUMO
OBJECTIVES: Adults born prematurely have an increased risk of early heart failure. The impact of prematurity on left and right ventricular function has been well documented, but little is known about the impact on the systemic vasculature. The goals of this study were to measure aortic stiffness and the blood pressure response to physiological stressors; in particular, normoxic and hypoxic exercise. METHODS: Preterm participants (n = 10) were recruited from the Newborn Lung Project Cohort and matched with term-born, age-matched subjects (n = 12). Aortic pulse wave velocity was derived from the brachial arterial waveform and the heart rate and blood pressure responses to incremental exercise in normoxia (21% O2 ) or hypoxia (12% O2 ) were evaluated. RESULTS: Aortic pulse wave velocity was higher in the preterm groups. Additionally, heart rate, systolic blood pressure, and pulse pressure were higher throughout the normoxic exercise bout, consistent with higher conduit artery stiffness. Hypoxic exercise caused a decline in diastolic pressure in this group, but not in term-born controls. CONCLUSIONS: In this first report of the blood pressure response to exercise in adults born prematurely, we found exercise-induced hypertension relative to a term-born control group that is associated with increased large artery stiffness. These experiments performed in hypoxia reveal abnormalities in vascular function in adult survivors of prematurity that may further deteriorate as this population ages.
Assuntos
Aorta/fisiopatologia , Exercício Físico/fisiologia , Hipertensão/fisiopatologia , Doenças do Prematuro/fisiopatologia , Adulto , Aorta/patologia , Artérias Carótidas/patologia , Feminino , Frequência Cardíaca , Humanos , Hipertensão/etiologia , Hipertensão/patologia , Doenças do Prematuro/patologia , Masculino , Análise de Onda de Pulso/métodos , Sobreviventes , Rigidez Vascular , Adulto JovemRESUMO
Importance: Premature birth is associated with substantially higher lifetime risk for cardiovascular disease, including arrhythmia, ischemic disease, and heart failure, although the underlying mechanisms are poorly understood. Objective: To characterize cardiac structure and function in adolescents and young adults born preterm using cardiac magnetic resonance imaging (MRI). Design, Setting, and Participants: This cross-sectional cohort study at an academic medical center included adolescents and young adults born moderately to extremely premature (20 in the adolescent cohort born from 2003 to 2004 and 38 in the young adult cohort born in the 1980s and 1990s) and 52 age-matched participants who were born at term and underwent cardiac MRI. The dates of analysis were February 2016 to October 2019. Exposures: Premature birth (gestational age ≤32 weeks) or birth weight less than 1500 g. Main Outcomes and Measures: Main study outcomes included MRI measures of biventricular volume, mass, and strain. Results: Of 40 adolescents (24 [60%] girls), the mean (SD) age of participants in the term and preterm groups was 13.3 (0.7) years and 13.0 (0.7) years, respectively. Of 70 adults (43 [61%] women), the mean (SD) age of participants in the term and preterm groups was 25.4 (2.9) years and 26.5 (3.5) years, respectively. Participants from both age cohorts who were born prematurely had statistically significantly smaller biventricular cardiac chamber size compared with participants in the term group: the mean (SD) left ventricular end-diastolic volume index was 72 (7) vs 80 (9) and 80 (10) vs 92 (15) mL/m2 for adolescents and adults in the preterm group compared with age-matched participants in the term group, respectively (P < .001), and the mean (SD) left ventricular end-systolic volume index was 30 (4) vs 34 (6) and 32 (7) vs 38 (8) mL/m2, respectively (P < .001). Stroke volume index was also reduced in adolescent vs adult participants in the preterm group vs age-matched participants in the term group, with a mean (SD) of 42 (7) vs 46 (7) and 48 (7) vs 54 (9) mL/m2, respectively (P < .001), although biventricular ejection fractions were preserved. Biventricular mass was statistically significantly lower in adolescents and adults born preterm: the mean (SD) left ventricular mass index was 39.6 (5.9) vs 44.4 (7.5) and 40.7 (7.3) vs 49.8 (14.0), respectively (P < .001). Cardiac strain analyses demonstrated a hypercontractile heart, primarily in the right ventricle, in adults born prematurely. Conclusions and Relevance: In this cross-sectional study, adolescents and young adults born prematurely had statistically significantly smaller biventricular cardiac chamber size and decreased cardiac mass. Although function was preserved in both age groups, these morphologic differences may be associated with elevated lifetime cardiovascular disease risk after premature birth.