scholarly journals Evidence of microvascular dysfunction in patients with cystic fibrosis

2016 ◽  
Vol 310 (11) ◽  
pp. H1479-H1485 ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Jeffrey Thomas ◽  
Nichole Seigler ◽  
Reva Crandall ◽  
Kathleen T. McKie ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Exercise Capacity ◽  
Reactive Hyperemia ◽  
Clinical Manifestations ◽  
Microvascular Dysfunction ◽  
Forced Expiratory Volume ◽  
Microvascular Function ◽  
Doppler Imaging ◽  
Control Subjects ◽  
Positive Correlations

Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 ± 174% (CF) and 801 ± 125% (control), P = 0.039], LTH [1,338 ± 436% (CF) and 1,574 ± 620% (control), P = 0.045], and iontophoresis with ACh [416 ± 140% (CF) and 617 ± 143% (control), P = 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly ( P = 0.043) lower in patients with CF (55.3 ± 5.1%) than control subjects (68.8 ± 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) ( r = 0.441, P = 0.013) and between the PORH-to-LTH ratio and exercise capacity ( r = 0.350, P = 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF.

scholarly journals Reproducibility and normalization of reactive hyperemia using laser speckle contrast imaging

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244795
Author(s):  
Behnia Rezazadeh Shirazi ◽  
Rudy J. Valentine ◽  
James A. Lang
Keyword(s):  
Reactive Hyperemia ◽  
Intraclass Correlation ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Rate Of Change ◽  
Laser Speckle ◽  
Maximal Flow ◽  
Contrast Imaging ◽  
Laser Speckle Contrast Imaging ◽  
Speckle Contrast

Background Impaired perfusion indices signal potential microvascular dysfunction preceding atherosclerosis and other cardiometabolic pathologies. Post-occlusive reactive hyperemia (PORH), a vasodilatory response following a mechanically induced ischemia, is a transient increase in perfusion and can assess microvascular function. The greatest blood flow change corresponding to the first minute of hyperemia (represented by time-to-peak, hyperemic velocity, AUC within 1st min) has been shown to indicate microvascular dysfunction. However, the reproducibility of these temporal kinetic indices of the PORH response is unknown. Our aim was to examine the inter- and intra-day reproducibility and standardization of reactive hyperemia, with emphasis on the kinetic indices of PORH, using laser speckle contrast imaging (LSCI) technique. Methods and results Seventeen healthy adults (age = 24 ± 3 years) completed three PORH bouts over two lab visits. LSCI region of interest was a standardized 10 cm region on the dominant ventral forearm. A 5-min brachial artery occlusion period induced by inflating an arm cuff to 200 mmHg, preceded a 4-min hyperemic period. Inter- and intra-day reliability and reproducibility of cutaneous vascular conductance (LSCI flux / mean arterial pressure) were determined using intraclass correlation (ICC) and coefficient of variation (CV%). Maximal flow and area under the curve standardized to zero perfusion showed intra- and inter-day reliability (ICC > 0.70). Time to maximal flow (TMF) was not reproducible (inter-day CV = 18%). However, alternative kinetic indices such as 1-min AUC and overshoot rate-of-change (ORC), represented as a piecewise function (at 5s, 10s, 15s, and 20s into hyperemia), were reproducible (CV< 11%). Biological zero was a reliable normalization point. Conclusion PORH measured with LSCI is a reliable assessment of microvascular function. However, TMF or its derived hyperemic velocity are not recommended for longitudinal assessment. Piecewise ORC and 1-min AUC are reliable alternatives to assess the kinetic response of PORH.

scholarly journals Age-Related Progression of Microvascular Dysfunction in Cystic Fibrosis: New Detection Ways and Clinical Outcomes

2021 ◽  
pp. 893-903
Author(s):  
M. Kreslová ◽  
A. Sýkorová ◽  
R. Bittenglová ◽  
J. Schwarz ◽  
R Pomahačová ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Vascular Disease ◽  
Vascular Tone ◽  
Disease Risk ◽  
Reactive Hyperemia ◽  
Microvascular Dysfunction ◽  
Reactive Hyperemia Index ◽  
Age Related ◽  
Profile Changes ◽  
Dimethyl Arginine

There are concerns about altered vascular functions that could play an important role in the pathogenesis and influence the severity of chronic disease, however, increased cardiovascular risk in paediatric cystic fibrosis (CF) has not been yet fully understood. Aim was to analyse vascular disease risk and investigate changes over times in CF and controls. We prospectively enrolled 22 CF subjects (a median age of 16.07 years), and 22 healthy demographically matched controls (a median age of 17.28 years) and determined endothelial function. We utilised a combined diagnostic approach by measuring the plethysmographic Reactive Hyperemia Index (RHI) as the post-to preocclusive endothelium-dependent changes of vascular tone, and biomarkers that are known to be related to endothelial dysfunction (ED): asymmetric dimethyl arginine (ADMA), high-sensitive CRP (hsCRP), VCAM-1 and E-selectin. RHI values were significantly lower in CF young adults (p<0.005). HsCRP (p<0.005), E-selectin (p<0.001) and VCAM-1 (p<0.001) were significantly increased in CF patients since childhood. The findings have provided a detailed account of the ongoing process of microvascular dysfunction with gradual progression with the age of CF patients, making them further at risk of advanced vascular disease. Elevations of biomarkers in CF children with not yet demonstrated RHI changes but with significantly reduced RHI in adulthood and lipid profile changes indicate the possible occurrence of ED with CF-related specific risk factors over time and will enable us to provide the best possible support.

scholarly journals Biatrial Remodeling in Patients with Cystic Fibrosis

2019 ◽  
Vol 8 (8) ◽  
pp. 1141 ◽  
Author(s):  
Aleksandar Dordevic ◽  
Martin Genger ◽  
Carsten Schwarz ◽  
Cesare Cuspidi ◽  
Elvis Tahirovic ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Ventricular Remodeling ◽  
Statistical Significance ◽  
Strain Analysis ◽  
Forced Expiratory Volume ◽  
Right Atrial ◽  
Predictors Of Mortality ◽  
Control Subjects ◽  
Left And Right ◽  
And Gender

Background: Previous studies have focused on left and right ventricular remodeling in cystic fibrosis (CF), whereas atrial function has not been assessed in detail so far. We sought to investigate left and right atrial (LA and RA) function in patients with CF. Methods: This retrospective investigation included 82 CF patients (64 survivors and 18 non-survivors) who were referred to CF department over the period of four years, as well as 32 control subjects matched by age and gender. All participants underwent an echocardiographic examination including a strain analysis, which was performed offline and blinded for groups. Results: LA and RA volume indexes were significantly higher in CF patients than in controls and were particularly high in CF non-survivors. LA conduit and reservoir functions were significantly worse in CF survivors and non-survivors, compared with control subjects. RA phasic function was not different between controls, CF survivors and non-survivors. The parameters of lung function (forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)) and the LA and RA volume indexes were predictors of mortality in CF patients. However, in a multivariate analysis, only FVC was an independent predictor of mortality in CF patients. Conclusions: Our results suggest that both atria are enlarged, but only LA function is impaired in CF patients. LA reservoir and conduit function is particularly deteriorated in CF patients. Though statistical significance was not reached due to our limited sample size, there was a trend of deterioration of LA and RA function from controls across CF survivors to CF non-survivors. LA and RA enlargement represented predictors of mortality in CF patients.

Noninvasive interrogation of microvasculature for signs of endothelial dysfunction in patients with chronic renal failure

2004 ◽  
Vol 287 (6) ◽  
pp. H2687-H2696 ◽  
Author(s):  
Julian Stewart ◽  
Adam Kohen ◽  
Daniel Brouder ◽  
Fahim Rahim ◽  
Stephen Adler ◽  
...  
Keyword(s):  
Fourier Analysis ◽  
Local Heating ◽  
Reactive Hyperemia ◽  
Clinical Manifestations ◽  
Laser Doppler ◽  
Doppler Imaging ◽  
Doppler Flowmetry ◽  
Valuable Adjunct ◽  
Increased Risk ◽  
Esrd Patients

Endothelial cell dysfunction (ECD) has been demonstrated in patients with end-stage renal disease (ESRD) who have cardiovascular disease (CD) or diabetes mellitus (DM). While techniques to examine conduit arteries have been adapted to these patients, evaluation of microvascular function has lagged behind. Therefore, we used laser Doppler flowmetry (LDF) and scanned laser Doppler imaging (LDI) to quantify parameters of the postocclusion reactive hyperemia and thermal hyperemic responses (local heating to 43°C) in ESRD patients ( n = 63) and healthy individuals ( n = 33). Patients with ESRD were partitioned among those with either CD or DM or both (designated CDorDM, n = 30), patients with both CD and DM (designated CD+DM, n = 12, statistically similar to CDorDM), and patients with neither CD or DM (designated ∼CDorDM, n = 33). LDF during thermal hyperemia showed a decrease in the thermal peaks and plateau as well as a delay in plateau compared with control, consistent with ECD. LDF during reactive hyperemia showed a decrease in the pay-back area under the curve, also consistent with ECD. ∼CDorDM were heterogeneous: almost 50% contained flow abnormalities similar to CDorDM. There was also a reduction in the number of functional arterioles on LDI images. Fourier analysis of LDF oscillations showed that low-frequency oscillations characterizing endothelial function were impaired in CDorDM and in many ∼CDorDM. The data demonstrate that ESRD patients with expected ECD (CDorDM) are characterized by distinct abnormalities in LDF parameters. However, similar abnormalities are found in approximately one-half of ESRD patients without evidence for CD or DM. Postocclusive and thermal interrogation of the microvasculature with laser Doppler-resolved parameters of the microcirculation, followed by Fourier analysis of the very slow oscillations, may provide a valuable adjunct to early noninvasive diagnosis of ECD in ESRD, especially important in a subpopulation of ESRD patients with no known CD or DM, which could be at increased risk of impending clinical manifestations of vasculopathy.

Increased resting energy expenditure in cystic fibrosis

1988 ◽  
Vol 64 (5) ◽  
pp. 1810-1816 ◽  
Author(s):  
R. M. Buchdahl ◽  
M. Cox ◽  
C. Fulleylove ◽  
J. L. Marchant ◽  
A. M. Tomkins ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Energy Expenditure ◽  
Resting Energy Expenditure ◽  
Forced Expiratory Volume ◽  
Whole Body ◽  
Clinical State ◽  
Control Subjects ◽  
Blood Leukocyte ◽  
Poor Pulmonary Function ◽  
Resting Energy

To explore the hypothesis that there is an increased metabolic rate in cystic fibrosis, resting energy expenditure was measured by indirect calorimetry in 23 subjects with cystic fibrosis in a stable clinical state and in 42 normal control subjects. Resting energy expenditure was found to be elevated by an average of 0.45 MJ/24 h [95% confidence interval (CI) = 0.26–0.64, t = 4.91, P less than 0.001] (108 kcal/24 h), or 9.2% above expected values derived from the regression relating resting energy expenditure to whole body weight and sex in control subjects. When related to lean body mass, values were still elevated by 0.36 MJ/24 h (95% CI = 0.18–0.53, t = 4.15, P less than 0.001) (86 kcal/24 h), or 7.2%. The increased values were found to be independent of age, sex, or body size. There were significant correlations between increased values and poor pulmonary function as measured by the ratio of the forced expiratory volume in 1 s to forced vital capacity (r = -0.44, P less than 0.05) and subclinical infection as indicated by the blood leukocyte count (r = 0.40, P less than 0.05). However, the correlations were low, suggesting that other factors may contribute to the increased resting energy expenditure, possibly including the putative metabolic defect in cystic fibrosis.

scholarly journals Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Massimo Nardone ◽  
Steven Miner ◽  
Mary McCarthy ◽  
Heather Edgell
Keyword(s):  
Stress Testing ◽  
Acute Exercise ◽  
Reactive Hyperemia ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Exercise Stress ◽  
Exercise Stress Testing ◽  
Coronary Microvascular Dysfunction ◽  
Vascular Assessment ◽  
Flow Reserve

Abstract Background The effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD. Methods In a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia. Results LnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34). Conclusions CMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

Analysis of factors limiting maximal exercise performance in cystic fibrosis

1992 ◽  
Vol 83 (4) ◽  
pp. 391-397 ◽  
Author(s):  
Larry C. Lands ◽  
George J. F. Heigenhauser ◽  
Norman L. Jones
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lean Body Mass ◽  
Exercise Capacity ◽  
Muscle Mass ◽  
Body Mass ◽  
Exercise Performance ◽  
Maximal Exercise ◽  
Control Subjects ◽  
Peripheral Muscle

1. Maximal exercise capacity in cystic fibrosis is influenced by both pulmonary and nutritional factors: lung disease by limiting maximal achievable ventilation, and malnutrition through a loss of muscle mass. The associated reduction in everyday activities may result in peripheral muscle deconditioning. 2. We studied 14 stable patients with cystic fibrosis (six males, eight females) and 14 healthy control subjects (seven males, seven females) in order to assess the influence of these factors on exercise performance. Subjects underwent anthropometry to estimate muscle mass, spirometry to assess ventilatory capacity, a 30 s sprint on an isokinetic cycle ergometer to assess maximal leg muscle performance, and progressive cycle ergometry to assess overall exercise capacity. 3. Compared with control subjects, the patients with cystic fibrosis were of similar age and height but weighed proportionately less [% ideal weight (mean ± sd): 94.3 ± 9.64 versus 109.5 ± 11.82] and showed evidence of airflow limitation [forced expiratory volume in 1.0s (FEV1.0) 72.5 ± 24.78 versus 112.6 ± 14.25% of predicted]. 4. The patients with cystic fibrosis did less absolute (5.1 ± 1.89 versus 7.3 ± 1.97 kJ) but similar relative maximal (11.5 ± 3.41 versus 13.1 ± 3.55 kJ/kg lean body mass) sprint work. During progressive exercise, the group with cystic fibrosis achieved lower absolute [maximal O2 consumption (Vo2max.) 1.8 ± 0.527 versus 3.0 ± 0.655 litres/min] and relative (Vo2max./kg lean body mass: 40.5 ± 9.23 versus 53.0 ± 11.62 ml min−1kg−1) work levels. 5. Step-wise linear regression was carried out with Vo2max. as the dependent variable and lean body mass, FEV1.0 and 30 s sprint work as independent variables. Vo2max. was best accounted for by a two-factor equation with FEV1.0 and 30 s sprint work (r2 = 0.882), with FEV1.0 being relatively more important. 6. While noting the importance of lung disease as a limiting factor, these results suggest that peripheral muscle function is a more sensitive determinant of maximal performance than lean body mass. The 30 s sprint work results imply that the effects of mild malnutrition in cystic fibrosis are quantitative, affecting the size of the muscle mass but not the performance of the remaining muscle.

scholarly journals High Frequency of Microvascular Dysfunction in US Outpatient Clinics: A Sign of High Residual Risk? Data from 7,105 Patients

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Morteza Naghavi ◽  
Stanley Kleis ◽  
Hirofumi Tanaka ◽  
Albert A. Yen ◽  
Ruoyu Zhuang ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Reactive Hyperemia ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Residual Risk ◽  
Outpatient Clinics ◽  
Reactivity Index ◽  
Maximum Temperature ◽  
Thermal Monitoring ◽  
Arterial Tonometry

Previous studies have linked peripheral microvascular dysfunction measured by arterial tonometry to high residual risk in on-statin patients. Digital thermal monitoring (DTM) of microvascular function is a new and simplified technique based on fingertip temperature measurements that has been correlated with the burden of atherosclerosis and its risk factors. Here, we report analyses of DTM data from two large US registries: Registry-I (6,084 cases) and Registry-II (1,021 cases) across 49 US outpatient clinics. DTM tests were performed using a VENDYS device during a 5-minute arm-cuff reactive hyperemia. Fingertip temperature falls during cuff inflation and rebounds after deflation. Adjusted maximum temperature rebound was reported as vascular reactivity index (VRI). VRI distributions were similar in both registries, with mean ± SD of 1.58 ± 0.53 in Registry-I and 1.52 ± 0.43 in Registry-II. In the combined dataset, only 18% had optimal VRI (≥2.0) and 82% were either poor (<1.0) or intermediate (1.0-2.0). Women had slightly higher VRI than men ( 1.62 ± 0.56 vs. 1.54 ± 0.47 , p < 0.001 ). VRI was inversely but mildly correlated with age ( r = − 0.19 , p < 0.001 ). Suboptimal VRI was found in 72% of patients <50 years, 82% of 50-70 years, and 86% of ≥70 years. Blood pressure was not correlated with VRI. In this largest registry of peripheral microvascular function measurements, suboptimal scores were highly frequent among on-treatment patients, possibly suggesting a significant residual risk. Prospective studies are warranted to validate microvascular dysfunction as an indicator of residual risk.

scholarly journals IL-8 correlates with reduced baseline femoral neck bone mineral density in adults with cystic fibrosis: a single center retrospective study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Grace Y. Lam ◽  
Sameer Desai ◽  
Joey Fu ◽  
Xun Yang Hu ◽  
Jiah Jang ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Cystic Fibrosis ◽  
Femoral Neck ◽  
Bone Mineral ◽  
Forced Expiratory Volume ◽  
Inflammatory Biomarkers ◽  
Mineral Density ◽  
Baseline Serum ◽  
Average Percentage ◽  
System Disease

AbstractCystic fibrosis (CF) is a multi-system disease that is characterized by lung disease due to recurrent airway infection and inflammation. Endocrine complications, such as CF bone disease (CFBD), are increasingly identified as patients are living longer. The cause of CFBD is multifactorial with chronic systemic inflammation theorized to be a contributing factor. Thus, we attempted to identify inflammatory biomarkers that are associated with CFBD. We conducted a retrospective observational study of 56 adult patients with CF with an average percentage predictive forced expiratory volume in one second (ppFEV1) of 73.7% (standard deviation: 30.0) who underwent baseline serum analysis for osteoprotegerin (OPG) and pro-inflammatory biomarkers (IL-1β, IL-6, IL-8 and TNF-α), and had repeated dual-energy x-ray absorptiometry (DXA) scans separated by at least 2 years to examine correlations between serum biomarkers and bone mineral density (BMD) measurements. Univariate linear regression model analysis demonstrated that serum IL-1β and IL-8, but not other pro-inflammatory markers, were negatively correlated with baseline BMD results. However, after accounting for confounding variables, only the relationship between IL-8 and left femoral neck BMD remained statistically significant. Additionally, IL-8 level was associated with BMD decline over time. These results suggest that IL-8 might play a unique role in the pathophysiology of CFBD relative to other pro-inflammatory cytokines but further study is warranted before firm conclusions can be made.

Sign in / Sign up

Export Citation Format

Share Document