Impaired Hemodynamic Response Research Articles

Changes in hemodynamic response function components reveal specific changes in neurovascular coupling in type 2 diabetes.

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease that leads to multiple vascular complications with concomitant changes in human neurophysiology, which may lead to long-term cognitive impairment, and dementia. Early impairments of neurovascular coupling can be studied using event-related functional magnetic resonance imaging (fMRI) designs. Here, we aimed to characterize the changes in the hemodynamic response function (HRF) in T2DM to probe components from the initial dip to late undershoot. We investigated whether the HRF morphology is altered throughout the brain in T2DM, by extracting several parameters of the fMRI response profiles in 141 participants (64 patients with T2DM and 77 healthy controls) performing a visual motion discrimination task. Overall, the patients revealed significantly different HRFs, which extended to all brain regions, suggesting that this is a general phenomenon. The HRF in T2DM was found to be more sluggish, with a higher peak latency and lower peak amplitude, relative slope to peak, and area under the curve. It also showed a pronounced initial dip, suggesting that the initial avidity for oxygen is not compensated for, and an absent or less prominent but longer undershoot. Most HRF parameters showed a higher dispersion and variability in T2DM. In sum, we provide a definite demonstration of an impaired hemodynamic response function in the early stages of T2DM, following a previous suggestion of impaired neurovascular coupling. The quantitative demonstration of a significantly altered HRF morphology in separate response phases suggests an alteration of distinct physiological mechanisms related to neurovascular coupling, which should be considered in the future to potentially halt the deterioration of the brain function in T2DM.

Susceptibility of aged pericytes to Aβ1‐42 oligomers

AbstractBackgroundAging is associated with increased incidence of Alzheimer’s disease, blood brain barrier breakdown, and increased cellular senescence (Saez‐Atienzar et. al, 2020). Senescence is the permanent arrest of the proliferative state of the cell and is initiated as a result of aging and cellular stress (Martínez‐Cué et.al, 2020). Senescent cells induce production of proinflammatory cytokines. In the brain, chronic inflammation leads to synapse damage and cognitive decline (Saez‐Atienzar et. al, 2020). The objective of this study is to examine the impact of cellular senescence on brain vascular pericytes, which contribute to the regulation of cerebral blood flow.MethodFor this study, both in vitro as well as in vivo experiments were performed. To induce senescence by oxidative stress in vitro in a culture of mouse brain vascular pericytes, 100 uM of hydrogen peroxide was added to culture flasks. Senescence was confirmed in the treated cells via staining for β‐galactosidase, a known biomarker of senescent cells. The next steps for the in vitro aspects of this study include performing western blotting on senescent pericytes to determine if there is a differential expression of pericyte p75 neurotrophin receptor (p75NTR), which has a potential role in the impaired hemodynamic response and cell death in pericytes. Finally, cranial window procedures were performed on 18‐month‐old C57BL/6 mice followed by imaging the live brain tissue with a multiphoton microscope. While imaging, artificial cerebral spinal fluid (control animals) or 72 nM amyloid‐beta (Aβ)1‐42 oligomers were topically delivered to the brain surface to determine if Aβ1‐42 oligomers cause a significant reduction in erythrocyte flow through pericyte covered capillaries.ResultPreliminary data from the β‐galactosidase staining suggest that the hydrogen peroxide is an effective method for inducing senescence in mouse brain vascular pericytes. We have observed a decreased growth rate in cells treated with the hydrogen peroxide, further suggesting senescence in these cells.ConclusionThese findings characterize the impact of Aβ on pericyte contractility and could illuminate the role of senescence and aging on impaired hemodynamic responses because of dysfunctional pericytes.

Impaired hemodynamic response to exercise in patients with peripheral artery disease: evidence of a link to inflammation and oxidative stress.

An exaggerated mean arterial blood pressure (MAP) response to exercise in patients with peripheral artery disease (PAD), likely driven by inflammation and oxidative stress and, perhaps, required to achieve an adequate blood flow response, is well described. However, the blood flow response to exercise in patients with PAD actually remains equivocal. Therefore, eight patients with PAD and eight healthy controls completed 3 min of plantar flexion exercise at both an absolute work rate (WR) (2.7 W, to evaluate blood flow) and a relative intensity (40%WRmax, to evaluate MAP). The exercise-induced change in popliteal artery blood flow (BF, Ultrasound Doppler), MAP (Finapress), and vascular conductance (VC) were quantified. In addition, resting markers of inflammation and oxidative stress were measured in plasma and muscle biopsies. Exercise-induced ΔBF, assessed at 2.7 W, was lower in PAD compared with controls (PAD: 251 ± 150 vs. Controls: 545 ± 187 mL/min, P < 0.001), whereas ΔMAP, assessed at 40%WRmax, was greater for PAD (PAD: 23 ± 14 vs. Controls: 11 ± 6 mmHg, P = 0.028). The exercise-induced ΔVC was lower for PAD during both the absolute WR (PAD: 1.9 ± 1.6 vs. Controls: 4.7 ± 1.9 mL/min/mmHg) and relative intensity exercise (PAD: 1.9 ± 1.8 vs. Controls: 5.0 ± 2.2 mL/min/mmHg) trials (both, P < 0.01). Inflammatory and oxidative stress markers, including plasma interleukin-6 and muscle protein carbonyls, were elevated in PAD (both, P < 0.05), and significantly correlated with the hemodynamic changes during exercise (r = -0.57 to -0.78, P < 0.05). Thus, despite an exaggerated ΔMAP response, patients with PAD exhibit an impaired exercise-induced ΔBF and ΔVC, and both inflammation and oxidative stress likely play a role in this attenuated hemodynamic response.

Correlation between impaired hemodynamic response and cardiopulmonary fitness in middle-aged type 2 diabetes mellitus patients: a case-control study.

Impaired cardiorespiratory fitness (CRF) is a predictor of mortality in patients with type 2 diabetes mellitus (T2DM). It is still not known how the exercise hemodynamic response correlates with CRF. The purpose was to assess the correlation between hemodynamic changes and CRF in middle-aged patients with T2DM. After 1:1 matching by age and sex, 139 T2DM patients and 139 non-T2DM controls who completed the exercise treadmill test were included. Maximal aerobic capacity (VO2max), exercise-induced changes in heart rate (ΔHR), systolic blood pressure (ΔSBP), diastolic blood pressure (ΔDBP), and rate-pressure product (ΔRPP) were measured. HRR1 was calculated as the maximum heart rate minus the heart rate after 1min of rest. Compared to the control population, T2DM patients had decreased ΔHR (87 (77, 97) v 93 (84, 104) bpm, p < 0.05), ΔRPP (3833.64 ± 1670.34 v 4381.16 ± 1587.78bpm∙mmHg, p < 0.05), HRR1 (21 (14, 27) v 21 (17, 27) bpm, p < 0.05), and VO2max (32.76 ± 5.63 v 34.68 ± 5.70ml/kg/min, p < 0.05). Multiple linear regression analysis showed that ΔHR and HRR1, yielded a positive correlation with VO2max in T2DM patients (β = 0.325, P < 0.001; β = 0.173, P = 0.01). The presence of impaired hemodynamic response and VO2max in middle-aged T2DM patients and the association of impaired ΔHR, HRR1, and VO2max may indicate a physiological pathway of impaired CRF, and our results support the need for cardiorespiratory screening and individualized treatment of middle-aged T2DM patients.

BLOOD PRESSURE ADAPTATIONS AND ARTERIAL STIFFNESS IN THE GENERAL POPULATION

Objective: Arterial stiffness is independently associated with orthostatic hypotension (OH) in older individuals. The relationship between orthostatic blood pressure (BP) and arterial stiffness has not been thoroughly examined in the younger population. To investigate the relationship between orthostatic BP adaptations, central aortic hemodynamics, and arterial stiffness in the general population of young and mid-aged adults. Design and method: A cross-sectional, observational, population-based study of 4223 individuals. We assessed arterial stiffness and central hemodynamics by carotid-femoral pulse wave velocity (c-f PWV) and pulse wave analysis (PWA) at the arteria radialis in relation to an orthostatic BP adaptation after 3 min standing. Results: The mean age of the population was 41.9 ± 14.5 years and 52.1% were women. We found that higher standing BP was associated with lower arterial stiffness after full adjustment in both men (unstandardized beta coefficient () -0.09, p = 0.02) and women (-0.08, p = 0.03). An increased diastolic BP on standing was inversely correlated with PWV and central aortic hemodynamics in both younger (PWV -0.01, p = 0.02) and older individuals (-0.02, p = 0.001). The lowest arterial stiffness was observed in the lowest and highest quartiles of standing systolic BP differences (p &lt; 0.001), while a gradual reduction in arterial stiffness was observed across increasing quartiles of standing diastolic BP difference for both PWV and measurements of central aortic hemodynamics (p &lt; 0.001). Conclusions: The co-existence of orthostatic hypotension, increased blood pressure variability, and vascular stiffness represents a hemodynamic ageing syndrome with important prognostic implications for public health. Our findings demonstrate that impaired hemodynamic response to orthostatic challenges, traditionally observed in older individuals, are independently and inversely associated with markers of arterial stiffness (vascular ageing) and hemodynamic changes also in a younger population. Further studies are required to assess the relationship between impaired blood pressure adaptations on standing in younger subjects and risk of future incident cardiovascular events.

Orthostatic hypotension and atrial fibrillation: is there a relationship?

Orthostatic hypotension (OH), a possible marker of autonomic dysfunction, reflects the inability of reflex cardiovascular mechanisms to compensate for the fall in venous return in the upright position. This is a manifestation of structural and functional abnormalities of the cardiovascular system. Significance of the orthostatic hypotension is underestimated, while it is associated with all-cause mortality and cardiovascular disease. The article reviews the relationship between atrial fibrillation (AF) and OH. The pathogenetic mechanisms of OH are considered, including various subgroups, e. g. elderly patients. The article also discusses the relationship between OH, AF and cerebrovascular complications. Available evidence suggests that impaired orthostatic hemodynamic response should be considered as a new risk factor for AF. Further research is needed for better understanding of the association between AF and OH, as well as their management.

Does arterial stiffness affect orthostatic hypotension among high-altitude Tibetans?

ABSTRACT Objective This study aimed to investigate the association between arterial stiffness and orthostatic hypotension (OH) and orthostatic blood pressure (BP) changes among Tibetans living at high altitude. Methods A total of 630 high-altitude Tibetans were included (56.53 ± 10.16 years; 246 men). Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). OH was defined as a decrease in systolic BP (SBP) >20 mmHg or a decrease in diastolic BP (DBP) >10 mmHg after 1 min or 3 min of moving from supine to standing position. Results The prevalence of OH in this population was 6.3%. Compared with subjects without OH, the subjects with OH had a higher baPWV (P < 0.001). Multiple logistical regression found that baPWV was significantly associated with the occurrence of OH (OR 1.147, CI 95% 1.028–1.280, P = 0.014). Spearman correlation analysis showed that baPWV was negatively associated with orthostatic changes in SBP and DBP(r = −0.256, P < 0.001 and r = −0.194, P < 0.001, respectively). Further multiple stepwise linear regression analysis showed that baPWV was independently correlated with orthostatic BP changes (SBP: β = −0.599, P < 0.001; DBP: β = −0.333, P < 0.001). Moreover, increased baPWV was correlated with attenuation of orthostatic heart rate changes. No significant association was observed between hematocrit or hemoglobin concentration and OH. Conclusion BaPWV was significantly associated with the occurrence of OH and orthostatic changes in the SBP and DBP, which suggests that arterial stiffness may be a potential mechanism of impaired hemodynamic response to orthostatic challenges among high-altitude Tibetans.

Impaired hemodynamic response to tilt, handgrip and Valsalva manoeuvre in patients with takotsubo syndrome.

Long-term β-adrenolytics treatment in takotsubo syndrome (TTS) patients is based on the premise, that TTS is strongly associated with sympathetic nervous system overactivity. The aim of the study was to establish hemodynamic response to tilt, handgrip and Valsalva manoeuvre in patients with takotsubo syndrome compared to healthy subjects (CONTROL) and patients after ST Elevation Myocardial Infarction (STEMI). Echocardiographic examination was performed at rest, ECG and continuously non-invasively measured arterial blood pressure were used for evaluation of hemodynamic responses to Valsalva manoeuvre, static handgrip (HG) followed by post-exercise ischemia, and tilt. Ten healthy women, 20 with TTS and 20 after STEMI, mean age 64 ± 8.5 years, participated in the study. Pressor response to Valsalva manoeuvre and tilt in TTS group was diminished in comparison to CONTROL and close to that of STEMI. During HG, increase of SBP was the lowest in TTS group. Data indirectly suggest that it was due to deficient stroke volume in TTS and STEMI patients during these manoeuvres; though echocardiographic findings at rest did not reveal any significant differences between groups. Our data show that despite apparent resolution of the immediate effects of TTS, impaired response to cardiovascular challenge, similar to that in STEMI patients, persisted. As the manoeuvres applied mimic daily life situations, causes of impairment should be searched for and potential health risk evaluated.

Exercise impedance cardiography reveals impaired hemodynamic responses to exercise in hypertensives with dyspnea.

Patients with arterial hypertension (AH), especially women, often report exercise intolerance and dyspnea. However, these symptoms are not frequently reflected in standard assessments. The aim of the study was to evaluate the clinical value of impedance cardiography (ICG) in the hemodynamic assessment of patients with AH during exercise, particularly the differences between subgroups based on sex and the presence of dyspnea. Ninety-eight patients with AH (52 women; 54.5 ± 8.2 years of age) were evaluated for levels of N-terminal pro-B-type brain natriuretic peptide (NT-proBNP), exercise capacity (cardiopulmonary exercise testing (CPET) and the 6-min walk test (6MWT)), and exercise ICG. Patients with AH were stratified into the following four subgroups: males without dyspnea (MnD, n = 38); males with dyspnea (MD, n = 8); females without dyspnea (FnD, n = 27); and females with dyspnea (FD, n = 25). In comparison with the MnD subgroup, the FnD subgroup demonstrated significantly higher NT-proBNP levels; lower exercise capacity (shorter 6MWT distance, lower peak oxygen uptake (VO2), lower O2 pulse); higher peak stroke volume index (SVI); and higher SVI at the anaerobic threshold (AT). In comparison with the other subgroups, the FD subgroup walked a shorter distance during the 6MWT distance; had a steeper VE/VCO2 slope; had lower values of peak stroke volume (SV) and peak cardiac output (CO); and had a smaller change in CO from rest to peak. However, no other differences were identified (NT-proBNP, left ventricular diastolic dysfunction, or CPET parameters). Exercise impedance cardiography revealed an impaired hemodynamic response to exercise in hypertensive females with dyspnea. In patients with unexplained exercise intolerance, impedance cardiography may complement traditional exercise tests.

Impaired Hemodynamic Response to Thermal Pain in Painful Diabetic Neuropathy

Objective: Painful diabetic peripheral neuropathy (painful-DPN) causes distressing neuropathic pain that is only partially responsive to treatment. A better understanding of CNS correlates of painful-DPN is vital to develop more effective therapeutics. The aim of this study was to measure cerebral perfusion of the pain processing areas of the brain using MR-Dynamic Susceptibility Contrast (MR-DSC) imaging at rest and under experimental pain condition. Methods: 55 T1DM subjects (20 painful-DPN, 23 painless-DPN, 13 no-DPN) and 19 Healthy Volunteers (HV); underwent detailed clinical and neurophysiological assessment (NISLL+7 tests of nerve function; DN4 questionnaire). MR images were obtained at 3T using a MR-DSC, T2*-weighted technique (TR/TE=1250/35ms; 72 dynamics) to assess the passage of a bolus of intravenous gadolinium-chelate through cerebral vascular bed. Subjects were scanned at baseline and during 90s of heat-pain applied to the right lateral thigh (non-neuropathic area). The time-to-peak (TTP) concentration of gadolinium in regions of interest (ROI): right and left thalamus, right and left sensory cortices (RSC and LSC), was measured. Results: At baseline, although the mean TTP (s) in the ROIs was shorter in the painful-DPN group [e.g., RT: M (SD): 9.22 (1.13) vs. HV 9.83 (0.99), no-DPN 9.59 (0.90), painless-DPN 9.94 (0.97)] this was not statistically significant (p=0.058). However the ΔTTP in response to thermal pain was significantly different between the groups LT (p=0.021), RT (p=0.003), LSC (p=0.009), RSC (p=0.008). Whilst HV respond to thermal pain by shortening the TTP in ROI the painful-DPN group do the reverse (p&amp;lt;0.05). Conclusion: Subjects with painful-DPN have a paradoxical increase in TTP, indicating that chronic neuropathic pain state may result in a failure to mount a hemodynamic response to external pain and descending inhibition. This novel finding may serve as an objective marker of painful-DPN, and in the future may facilitate the development of novel treatments. Disclosure M. Greig: None. I.D. Wilkinson: None. D. Selvarajah: None. P. Shillo: None. R. Gandhi: None. S. Tesfaye: Speaker's Bureau; Self; Pfizer Inc.. Other Relationship; Self; Janssen Pharmaceuticals, Inc., Takeda Development Centre Europe Ltd.. Advisory Panel; Self; Wörwag Pharma GmbH &amp; Co. KG.

EXERCISE IMPEDANCE CARDIOGRAPHY REVEALS IMPAIRED HEMODYNAMIC RESPONSE TO EXERCISE IN HYPERTENSIVES WITH DYSPNEA

Objective: Patients with arterial hypertension (AH), especially women, often report exercise intolerance and dyspnea. However, subjective symptoms are frequently not reflected in standard, objective assessments. The aim of the study was to assess multiple parameters during controlled exercise in patients with AH, particularly the differences between subgroups identified based on sex and symptoms of reduced exercise tolerance. Design and method: Ninety-eight patients with AH (52 women; age 54.5 ± 8.2 years) were evaluated for dyspnea, levels of the NT-proBNP, exercise capacity (with cardiopulmonary exercise testing (CPET) and a 6-minute walk test (6MWT)), and hemodynamic parameters (by means of impedance cardiography) during exercise. Patients with AH were stratified by sex and history of dyspnea, yielding four subgroups: males without dyspnea (MnD, n = 38); males with dyspnea (MD, n = 8); females without dyspnea (FnD, n = 27); females with dyspnea (FD, n = 25). Results: In comparison with MnD, the FnD subgroup demonstrated higher NT-proBNP levels (29.5 ± 25.5 vs. 103.1 ± 71.6 pg/mL, p < 0.001); lower exercise capacity: shorter 6MWT distance (595.3 ± 91.5 vs. 522.9 ± 56.6 m, p < 0.001); lower peak oxygen uptake (VO2) (22.7 ± 5.2 vs. 17.0 ± 3.7 mL/min/kg, p < 0.001); higher peak stroke volume index (SVI) (52.4 ± 8.9 vs. 61.7 ± 11.2 mL/m2, p = 0.004); and higher SVI at the anaerobic threshold (AT) (50.1 ± 10.4 vs. 59.5 ± 12.6 mL, p = 0.011). In comparison with FnD, the FD subgroup covered a shorter distance during the 6MWT distance (522.9 ± 56.6 vs. 466.1 ± 87.2 m, p = 0.017), had a steeper VE/VCO2 slope (25.5 ± 2.4 vs. 29.0 ± 5.5, p = 0.004); lower values of peak stroke volume (SV) (117.4 ± 22.4 vs. 99.7 ± 18.1 mL, p = 0.017), peak cardiac output (CO) (17.0 ± 3.7 vs. 13.1 ± 2.9 L/min, p = 0.002) and lower change in CO (peak–rest) (10.5 ± 3.6 vs. 7.2 ± 2.7 L/min, p = 0.004). However, no other differences were identified (NT-proBNP, left ventricular diastolic dysfunction, or CPET parameters) Conclusions: Exercise impedance cardiography revealed an impaired hemodynamic response to exercise in hypertensive females with dyspnea. In patients with unexplained exercise intolerance exercise impedance cardiography may complement traditional exercise tests.

Arterial hemodynamics are impaired at rest and following acute exercise in overweight young men.

Higher body mass index (BMI) is associated with greater cardiovascular disease (CVD) risk, in part due to aortic stiffening assessed by carotid-femoral pulse wave velocity (cfPWV). Importantly, greater cardiorespiratory fitness (CRF; VO2peak) decreases CVD risk, and is associated with reductions in aortic stiffness. We tested the hypothesis that young adult overweight (OW, n=17) compared with healthy-weight (HW, n=17) men will have greater resting aortic stiffness, reduced CRF and an impaired post-exercise hemodynamic response. Resting cfPWV was greater in OW versus HW individuals (5.81 ± 0.13 vs 4.81 ± 0.12 m/sec, p<0.05). Relative CRF (VO2peak; mL/kg/min) was lower in OW compared with HW individuals (49.4 ± 1.3 vs 57.6 ± 1.0 mL/kg/min, p<0.05), and was inversely related with cfPWV (p<0.05). However, CRF as absolute VO2peak (L/min) was not different between groups and there was no relation between cfPWV and absolute VO2peak (L/min), indicating reduced relative CRF in OW men is due to greater body mass. Following the maximal treadmill exercise test, cfPWV was greater in OW compared with HW subjects from rest to 60 minutes post-exercise (p<0.05). Compared with HW, OW individuals had higher systolic blood pressure (main effect, p<0.05) and diastolic blood pressure was selectively increased for up to 60 minutes following exercise (p<0.05). Overweight individuals had an attenuated post-exercise decrease in mean arterial pressure (p<0.05). Collectively, these results indicate that young, apparently healthy, OW men have greater resting aortic stiffening and an impaired post-exercise hemodynamic response.

G-Protein-Coupled Receptor MrgD Is a Receptor for Angiotensin-(1-7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A.

Angiotensin (Ang)-(1-7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin-angiotensin system. Although it is well accepted that the G-protein-coupled receptor Mas is a receptor for the heptapeptide, the lack in knowing initial signaling molecules stimulated by Ang-(1-7) prevented definitive characterization of ligand/receptor pharmacology as well as identification of further hypothesized receptors for the heptapeptide. The study aimed to identify a second messenger stimulated by Ang-(1-7) allowing confirmation as well as discovery of the heptapeptide's receptors. Ang-(1-7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, we provided pharmacological proof that Mas is a functional receptor for Ang-(1-7). Moreover, we identified the G-protein-coupled receptor MrgD as a second receptor for Ang-(1-7). Consequently, the heptapeptide failed to increase cAMP concentration in primary mesangial cells with genetic deficiency in both Mas and MrgD Mice deficient in MrgD showed an impaired hemodynamic response after Ang-(1-7) administration. Furthermore, we excluded the Ang II type 2 receptor as a receptor for the heptapeptide but discovered that the Ang II type 2 blocker PD123319 can also block Mas and MrgD receptors. Our results lead to an expansion and partial revision of the renin-angiotensin system, by identifying a second receptor for Ang-(1-7), by excluding Ang II type 2 as a receptor for the heptapeptide, and by enforcing the revisit of such publications which concluded Ang II type 2 function by only using PD123319.

Comparison Between Impedance Cardiography And Echocardiography During Metaboreflex Activation In Heart Failure

The possibility to increase stroke volume (SV) has been shown to be crucial to reach a normal blood pressure (BP) response during the muscle metaboreflex (MM). Healthy individuals have the capacity to increase myocardial contractility and SV during the MM, thereby increasing cardiac output. This phenomenon avoids excessive vasoconstriction and exaggerated systemic vascular resistance (SVR) increments to achieve the target BP, whereas in patients with chronic heart failure (CHF) SV can not increase and this leads to vasoconstriction with an exaggerated SVR response1. However, SV is not easily assessed non-invasively in humans and several methods have been proposed to this aim. PURPOSE: to compare two methods to measure SV during the MM in patients with chronic heart failure (CHF). METHODS: 10 male CHF patients (age between 44-68 years, 5 classified as being in the NYHA functional class II, whereas the other 5 were in the NYHA class III) took part in this investigation. Their mean ± SD of ejection fraction EF was 30.5±4.8%. Participants underwent a post-exercise muscle ischemia (PEMI) test, to study the hemodynamic changes during the MM activation. Response in SV during the PEMI maneuver was studied with two METHODS: impedance cardiography and Doppler echocardiography. Differences between the two methods was carried out by means of the paired t test. Moreover, the Bland and Altman plot was utilized to estimate agreement between methods. RESULTS: statistics did not find out any difference between impedance cardiography and Doppler Echocardiography. Furthermore, the Bland and Altman plot showed a good agreement between methods, with a mean difference of 0.75 ml and with 95% limits of agreement between 13.05 and -11.53 ml. CONCLUSIONS: data from this study suggest that the two methods to assess SV during MM activation provide similar and interchangeable results. 1Crisafulli A et al. Impaired central hemodynamic response and exaggerated vasoconstriction during muscle metaboreflex activation in heart failure patients. Am J Physiol (Heart Circ Physiol) 2007; 292: H2988-H2996.

Diastolic heart failure: diagnosis and therapy.

This article focuses on the recent findings in the diagnosis and treatment of diastolic heart failure (DHF) or heart failure with preserved ejection fraction. DHF has become the most common form of heart failure in the population. Although diastolic dysfunction still plays a central role, it is now understood that DHF is a very complex clinical entity with heterogeneous pathophysiology and significant contribution from extracardiac comorbidities. Alterations in ventricular-arterial coupling play a significant role in the impaired hemodynamic response to exercise seen in these patients. The absence of diastolic dysfunction at rest does not exclude the diagnosis of DHF. There has been little to no progress made in identifying evidence-based, effective, and specific treatments for patients with DHF. This may be because of the pathophysiological heterogeneity, incomplete understanding of DHF, and heterogeneity of patients included in clinical trials with variable inclusion criteria. The understanding of the phenotypic heterogeneity and multifactorial pathophysiology of DHF may lead to novel therapeutic targets in the future. Currently, the key to the treatment of DHF is aggressive management of contributing factors.

Impaired Hyperemic Response to Exercise Post Stroke.

Individuals with chronic stroke have reduced perfusion of the paretic lower limb at rest; however, the hyperemic response to graded muscle contractions in this patient population has not been examined. This study quantified blood flow to the paretic and non-paretic lower limbs of subjects with chronic stroke after submaximal contractions of the knee extensor muscles and correlated those measures with limb function and activity. Ten subjects with chronic stroke and ten controls had blood flow through the superficial femoral artery quantified with ultrasonography before and immediately after 10 second contractions of the knee extensor muscles at 20, 40, 60, and 80% of the maximal voluntary contraction (MVC) of the test limb. Blood flow to the paretic and non-paretic limb of stroke subjects was significantly reduced at all load levels compared to control subjects even after normalization to lean muscle mass. Of variables measured, increased blood flow after an 80% MVC was the single best predictor of paretic limb strength, the symmetry of strength between the paretic and non-paretic limbs, coordination of the paretic limb, and physical activity. The impaired hemodynamic response to high intensity contractions was a better predictor of lower limb function than resting perfusion measures. Stroke-dependent weakness and atrophy of the paretic limb do not explain the reduced hyperemic response to muscle contraction alone as the response is similarly reduced in the non-paretic limb when compared to controls. These data may suggest a role for perfusion therapies to optimize rehabilitation post stroke.

Abstract 513: Impaired Hemodynamic Response to Head up Tilt in Adolescents Presenting with Chronic Nausea and Orthostatic Intolerance

We previously reported that ~70% of adolescents presenting to a Pediatric GI clinic for chronic nausea exhibit orthostatic intolerance (OI) in response to head upright tilt testing (HUT). The objective of this study was to determine whether supine mean arterial pressure or hemodynamic responses to HUT differ in these patients. Forty-eight patients (mean age of 15 [10-18] years, 36 females) completed a 45 minutes 0 to 70° HUT. Continuous blood pressure and heart rate recordings were acquired using non-invasive finger cuff. Thirteen subjects had normal tilt (Normal) while thirty five demonstrated OI. There were no differences between the two groups in supine blood pressures (BP), baroreflex sensitivity measured by frequency method in HF range (BRS), heart rate variability (HRV) measured as the root of mean square of successive differences (rMSSD), blood pressure variability (BPV) measured as standard deviation of mean arterial pressure (SDMAP) or the sympathovagal balance measure LF RRI /HF RRI . HUT caused a greater increase in heart rate in OI group (from 71 ± 6 beats/min to 104 ± 4 in OI vs from 75 ± 3 to 95 ±3 in normal, p=0.01) which was accompanied with lesser increase in BP (mainly due to lack of increase in diastolic) in the OI group. There was a trend for greater reduction in BRS in OI subjects (from 28.5 ± 13 ms/mm Hg to 6.3 ± 0.8 in OI vs from 21.1 ± 3.6 to 12.0 ± 2.9 in normal, p=0.09). HUT impaired HRV in both groups compared to supine values but the reduction was greater in OI group (-66.7 ± 4 % vs -52.0 ±5.6 in normal, p=&lt;0.001). SDMAP increased by HUT compared to supine but to a greater extent in OI (40.6 ± 4 % vs 13.4 ± 8 in normal, p=0.02). LF RRI /HF RRI increased to a greater magnitude in OI group with HUT (from 1.8 ± 0.8 to 6.8 ± 0.8 in OI vs from 1.14 ± 0.18 to 4.1 ±0.7 in normal, p=0.02). These data reveal that the adolescents with orthostatic intolerance have attenuated parasympathetic responses and exaggerated activation of the sympathetic system to the heart and blood vessels. Despite these responses, subjects fail to maintain BP. Similar to previous studies in other subjects with OI, the excessive tachycardia often followed by syncope in most of these adolescents may reflect a loss of vascular responses to the activation of sympathetic and neurohumoral stimuli. Support: AHA12CRP9420029

The Value of Exercise Stress Testing for Renal-Cardiac Risk Assessment in Military Personnel: Exploring the Hidden Half!

For decades, the exercise stress test (EST) has been known as a well-established non-invasive diagnostic test in patients with suspected or known cardiovascular disease (CVD). However, EST is also used for several other purposes in the armed forces including fitness assessment and adjustment training in simulated non-conventional environments such as altitude chambers. While exercise stress test is a part of periodic health check-up in specific groups of the military forces such as aviators, divers, and commanders, its diagnostic value for cardiovascular disease (CVD) detection is unclear in asymptomatic healthy subjects with low and intermediate cardiovascular risk according to the current clinical practice guidelines. Furthermore, it is demonstrated that it has a modest sensitivity and specificity for the diagnosis of coronary artery disease (67-72% and 69-90% respectively) in symptomatic patients. Hence, the hidden half of the test including non-electrical variations such as hemodynamic changes would be taken into the account or results of other tests such as arterial evaluations would be combined to provide a diagnostic battery. Meanwhile, its performance is also related to the CVD pre-test probability and the prevalence of the disease in the target population. On the other hand, not only the heart, but also vessels and kidneys can be evaluated by EST. Current evidence demonstrates that the hemodynamic response to exercise and exercise-induced micro-albuminuria are associated with cardiac, renal, and arterial functional status. In addition, impaired hemodynamic response to exercise predicts the development of renal dysfunction in the future. In conclusion, EST would be particularly important in the early detection of cardiac, vascular, and renal diseases in military personnel; however, justification and arrangements for the testing must be individually assessed, and this process can be facilitated by decision analysis methods. Keywords: Exercise Test; Risk Assessment; Diabetes Mellitus

Impaired hemodynamic response in the ischemic brain assessed with BOLD fMRI

The study aims to investigate the effect of cerebral ischemia or hypoperfusion in the evaluation of neural activity with blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI), and to examine whether the severity of the compromised hemodynamic status in patients with major cerebral artery diseases could, conversely, be assessed with the use of neural activity as endogenous vasodilator. 28 neurological impairment-free patients with anterior-circulation-territory ischemia performed a bimanual hand-grasping task. Magnitude and temporal shift of evoked BOLD response, baseline cerebral blood flow (CBF) and its increment, and the severity of hemodynamic impairment stratified by blood flow pattern were evaluated. For fMRI data, both conventional analysis with a canonical HRF and an HRF-model-free analysis were performed. The severity of hemodynamic impairment was significantly correlated (p<0.0001) with baseline CBF, CBF increment, and magnitude and delay of BOLD response. BOLD response delay was also significantly correlated (p<0.0001) with baseline CBF, CBF increment, and response magnitude. In 10 out of 45 ischemic motor cortices, conventional analysis completely failed to detect areas of activation that were demonstrated by HRF-model-free analysis. These data suggest that delay and reduced magnitude of BOLD response can be an indicator of the severity of compromised hemodynamic status, and that reduced regional baseline CBF and its increment underlie impaired BOLD response, which necessitates an alternative approach to conventional analysis with any single HRF.

Impact of endothelial nitric oxide synthase gene polymorphisms on hemodynamic after a bout of maximal dynamic exercise

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (NOS3) have been associated with lower eNOS expression and activation, which can lead to impairment in eNOS related traits. Thus, we investigated the individual (genotype analysis) and combined (haplotype analysis) impact of three polymorphisms in the NOS3 (−786T&gt;C, 4b4a and 894G&gt;T) on hemodynamic variables. Sedentary, non‐obese, healthy subjects were enrolled [n = 93, age 31 ± 9 years (mean ± SD)]. Genotypes were determined by PCR‐RFLP and haplotypes were inferred by a Bayesian based algorithm. Heart rate (ECG) and blood pressure (BP; finger photoplethismography) were continuously measured during 10 min in the supine position before [baseline (BL)], 10, 60 and 120 min after a maximal cardiopulmonary exercise test. Stroke volume was estimated by the Model Flow method. Then, cardiac output (CO) and total peripheral resistance (TPR) were calculated. There was no difference between subjects in genotype analysis. However, subjects with haplotype containing the polymorphisms −786T&gt;C and 4b4a had higher systolic BP at 10, 60 and 120 min after exercise than subjects with wild haplotype (P &lt; 0.05), which occurred due to higher CO (P &lt; 0.05), while TPR was similar between groups (P &gt; 0.05). In conclusion, NOS3 haplotype containing the polymorphisms −786T&gt;C and 4b4a was associated with impaired hemodynamic response after a bout of maximal dynamic exercise.