Impact of foam rolling with and without vibration on muscle oxidative metabolism and microvascular reactivity.

Background and Purpose: There is a growing interest in use vibration foam rolling as a warm up and recovery tool. However, whether vibration foam rolling offers additional benefits to traditional foam rolling is unclear. The current study aims to compare the effects of acute foam rolling, with and without vibration, on skeletal muscle metabolism and microvascular reactivity. Methods: Fifteen physically active young males were tested on two different days, with gastrocnemius muscle microvascular function assessed using near-infrared spectroscopy coupled with the post-occlusive reactive hyperemia technique, before and after foam rolling, performed with or without vibration. The slope of tissue saturation index (TSI) decrease during occlusion between 120 s to 150 s (TSI occlusion slope) was assessed for muscle metabolic rate. Three commonly used microvascular function indexes, including the first10s TSI slope after occlusion (TSI10), time for TSI to reach half of peak magnitude (TSI1/2), and TSI peak reactive hyperemia, were also assessed. Results: None of the measured indexes showed significance for interaction or method (all p > 0.05). However, there was a main effect for time for TSI occlusion slope, TSI1/2, and TSI peak reactive hyperemia (p = 0.005, 0.034 and 0.046, respectively). No main effect for time for TSI10 was detected (p = 0.963). Conclusions: The application of foam rolling can decrease muscle metabolism, and may improve some aspects of muscle microvascular function. However, vibration foam rolling does not seem to offer any additional benefits compared to traditional foam rolling alone.

Key Clinical and Histopathological Features of a Pterygium-Like Induced Lesion in a Rabbit Model.

Purpose: Surgery is the definitive treatment for pterygium; therefore, reliable animal models are required for translational research. The goal of this investigation was to establish a standardized preclinical model of pterygium-like lesion. Methods: A subconjunctival injection of fibroblasts (NIH3T3) and extracellular matrix was administered to 22 New Zealand rabbits. Clinical evaluation was assessed at different points, the severity of the lesion was scored according to four grades and correlated with the area of hyperemia and the histopathological findings on day 23. Results: Thirteen of 22 eyes (60%) developed pterygium-like lesions after 7 days and progressed through different grades. Initially, grade 3, characterized by an elevated and fleshiness conjunctiva with tortuous hyperemia, was evident on day 7. By day 15, lesion decreased to grade 2, with less elevation and hyperemia. Subsequent improvement was noted, with grade 1 on day 18. Finally, day 23 was marked by a white‒yellow lesion, classified as grade 4. The area of hyperemia increased from grade 2 to grade 3 (P < 0.05) and decreased from grade 3 to grade 4 (P ≤ 0.05). Histopathological analysis revealed a tendency toward increasing inflammation at grades 2, 3, and 4. There was a correlation between clinical features and the degree of inflammation. Conclusions: Subconjunctival injection of NIH3T3 and extracellular matrix induces a pterygium-like lesion that progresses across four grades, beginning with an acute inflammatory process that evolve a chronic form. This study provides a replicable model for simulating pterygium. Translational Relevance: The development of a standardized preclinical model of pterygium to evaluate new pharmacological or surgical treatments.

Partial Reconstruction of the Auricle With the Tubed Postauricular Flap: A Case Report and Proposed Innovation for Flap Conditioning.

The authors present a case of a partial auricular deformity acquired from a human bite that was reconstructed using a 3-stage posterior auricular tubed flap. Helical rim avulsions may be ideally reconstructed with a tubed flap created from lax postauricular soft tissue. During the third stage, division and inset of the inferior pedicle of the flap were complicated by venous congestion. The use of leech therapy and topical nitroglycerin successfully improved flap circulation. Given the occurrence of venous congestion due to a sudden change in flap blood circulation, the authors propose a pedicle compression device to be used in the future that assists with flap conditioning. This physiological delay helps minimize flap ischemia by allowing choke vessels to dilate within, thus increasing flap reliability. Therefore, when the pedicle is divided, improved circulation from the previously inset superior pedicle has been established with a decreased risk of venous congestion and arterial insufficiency.

Incidence, predictability, and outcomes of systemic venous congestion following a fluid challenge in initially fluid-tolerant preload-responders after cardiac surgery: a pilot trial.

BACKGROUND: Fluid administration has traditionally focused on preload responsiveness (PR). However, preventing fluid intolerance, particularly due to systemic venous congestion (VC), is equally important. This study evaluated the incidence and predictability of VC following a 7 ml/kg crystalloid infusion in fluid-tolerant preload-responders and its association with adverse outcomes. METHODS: This single-center, prospective, observational study (May 2023-July 2024) included 40 consecutive patients who were mechanically ventilated within 6 h of intensive care unit (ICU) admission after elective open-heart surgery and had acute circulatory failure. Patients were eligible if they were both fluid-tolerant and preload-responsive. PR was defined as a ≥ 12% increase in left-ventricular outflow tract velocity time integral (LVOT-VTI) 1 min after a passive leg raising (PLR) test. VC was defined by a portal vein pulsatility index (PVPI) ≥ 50%. Patients received a 7 ml/kg Ringer's Lactate infusion over 10 min. The primary outcome was the incidence of VC 2 min post-infusion (early-VC). Secondary outcomes included VC at 20 min, the incidence of acute kidney injury (AKI) and severe AKI at 7 days, and ICU length of stay (LOS). RESULTS: 45% of patients developed early-VC, with VC persisting in only 5% at 20 min. One-third of patients developed AKI, with 17.5% progressing to severe AKI. The median ICU LOS was 4 days. Patients with early-VC had significantly higher central venous pressure, lower mean perfusion pressure, worse baseline right ventricular function, and a higher incidence of severe AKI. While LVOT-VTI returned to baseline by 20 min in both groups, PVPI remained elevated in early-VC patients (p < 0.001). The LVOT-VTI versus PVPI regression line showed similar slopes (p = 0.755) but different intercepts (p < 0.001), indicating that, despite fluid tolerance and PR at baseline, early-VC patients had reduced right ventricular diastolic reserve (RVDR). Post-PLR PVPI predicted early-VC with an area under the curve of 0.998, using a threshold of 44.3% (p < 0.001). CONCLUSION: Post-PLR PVPI effectively predicts fluid-induced early-VC in fluid-tolerant preload-responders, identifying those with poor RVDR. Its use can guide fluid management in cardiac surgery patients, helping to prevent unnecessary fluid administration and associated complications. TRIAL REGISTRATION: NCT06440772. Registered 30 May 2024. Retrospectively registered.

Endothelial Piezo1 channel mediates mechano-feedback control of brain blood flow.

Hyperemia in response to neural activity is essential for brain health. A hyperemic response delivers O2 and nutrients, clears metabolic waste, and concomitantly exposes cerebrovascular endothelial cells to hemodynamic forces. While neurovascular research has primarily centered on the front end of hyperemia-neuronal activity-to-vascular response-the mechanical consequences of hyperemia have gone largely unexplored. Piezo1 is an endothelial mechanosensor that senses hyperemia-associated forces. Using genetic mouse models and pharmacologic approaches to manipulate endothelial Piezo1 function, we evaluated its role in blood flow control and whether it impacts cognition. We provide evidence of a built-in brake system that sculpts hyperemia, and specifically show that Piezo1 activation triggers a mechano-feedback system that promotes blood flow recovery to baseline. Further, genetic Piezo1 modification led to deficits in complementary memory tasks. Collectively, our findings establish a role for endothelial Piezo1 in cerebral blood flow regulation and a role in its behavioral sequelae.

Pulse transmission time and amplitude of digital pulse wave determined by fingertip plethysmography as a surrogate marker of brachial artery flowmediated dilatation.

OBJECTIVE: To assess the changes in blood vessel stiffness and digital pulse wave amplitude because of flowmediated dilatation, and to explore how these two variables change when endothelial dysfunction is experimentally induced. METHODS: The experimental study was conducted at the departments of physiology at the College of Medicine, Mustansiriyah University, and the College of Medicine, Al-Iraqia University, Baghdad, Iraq, from October 14, 2021, to May 31, 2022, and comprised healthy young males who were subjected to the flow-mediated dilatation technique on the left brachial artery. Pulse transit time and the amplitude of the digital pulse wave were measured during reactive hyperaemia for 2.5 minutes from the left middle finger using a piezoelectric pressure sensor and a simultaneous Lead I electrocardiogram. Endothelial dysfunction (ED) was induced by oscillatory and retrograde shear rates. The correlation between variables was calculated in Excel running on the Windows operating system. RESULTS: There were 10 second-year medical students with mean age 22±0 years and mean body mass index 25.7±4.8kg/m2. During reactive hyperaemia, pulse transit time was significantly increased by 3-5% in both normal endothelium and experimentally induced endothelial dysfunction relative to the pre-occluded artery, and the difference was not significant (p>0.05). Digital pulse wave amplitude increased significantly in normal endothelium relative to the pre-occluded artery (p<0.05), but not in experimentally-induced endothelial dysfunction (p>0.05). CONCLUSIONS: The pulse transit time and digital pulse wave amplitudes of the photo plethysmography signal may be used to detect changes in vessel wall diameter and tone throughout the reactive hyperaemia process. Digital pulse wave amplitude was better able to detect experimentally-induced endothelial dysfunction, as assessed by the flowmediated dilatation protocol, than pulse transit time.

The Effect of Venous Augmentation on Complication Rates in Deep Inferior Epigastric Perforator Breast Reconstruction.

BACKGROUND: With the rising popularity of the deep inferior epigastric perforator (DIEP) flap in breast reconstruction, use of the superficial inferior epigastric vein (SIEV) to augment venous outflow has been proposed as a strategy to prevent venous congestion, a complication positively associated with flap volume. This study evaluated the impact of routine SIEV venous augmentation on the risk of vascular complications or operative fat necrosis in the context of flap size and operating time. METHODS: A retrospective cohort study compared complication rates of patients with SIEV-augmented DIEP flaps to controls over a 3-year period. Outcomes assessed included vascular complications, defined as venous congestion or compromise requiring take-back, partial flap necrosis, total flap loss, as well as operative fat necrosis. Relative risk was modeled by Cox proportional hazard regression analysis. Sensitivity analysis was performed to assess for an interaction effect by flap mass. RESULTS: The study sample included 197 patients with 316 flaps. The mean mass of the SIEV-augmented flaps was significantly greater than in the control group (832.9 vs. 653.9 g; p = 0.0007). After adjustment for flap characteristics, patient demographic factors, and comorbidities, pooled risk of vascular complication and operative fat necrosis was found to be significantly lower in the SIEV-augmented group compared to controls (hazard ratio = 0.33, 95% CI [0.11-1.00]; p = 0.0489). Sensitivity analysis demonstrated no effect interaction by flap weight (p = 0.5139). CONCLUSION: Routine venous outflow augmentation via anastomosis of SIEV to the internal mammary vein perforator at the second intercostal space significantly reduced the risk of vascular complications and operative fat necrosis, regardless of flap weight. No significant increase in operative time was observed among cases in which augmentation was performed.

Acute impact of inorganic nitrate supplementation after ischemia and during small muscle mass exercise in postmenopausal females: A pilot study.

Menopause is associated with reduced endothelial-dependent vasodilation and increased cardiovascular disease (CVD) risk. Dietary nitrate, a non-pharmacological approach, may increase vasodilatory capacity consequentially reducing CVD risk. We investigated macro- and microvascular function after acute nitrate supplementation in postmenopausal females (PMF). Vascular function was studied with flow-mediated vasodilation (FMD) and near-infrared post occlusive reactive hyperemia (PORH). Incremental handgrip exercise was performed to investigate blood flow and tissue oxygenation. We hypothesized acute dietary nitrate would not impact resting endothelial measures but would increase post ischemic vasodilation and incremental exercise blood flow. Late-phase PMF (n = 12) participated in a randomized crossover design with 140 mL of nitrate-rich (NR) beetroot juice or nitrate-poor black currant juice. Testing included a 5-min FMD, a 3-min ischemic exercise FMD, and incremental exercise at 10%, 15%, and 20% maximal voluntary contraction to measure blood flow and pressure responses. A p ≤ 0.05 was considered significant. One-way ANOVA indicated lower resting pressures, but no change to FMD, or PORH in either protocol. Two-way repeated measures ANOVA indicated NR supplementation significantly reduced mean arterial pressure at rest and during incremental exercise at all intensities without changes to blood flow. Acute nitrate is effective for resting and exercising blood pressure management in PMF.

[Effectiveness of the Eye Care Protocol in the Intensive Care Unit Patients: A Randomized Controlled Trial].

PURPOSE: This study investigated the effects of an eye care protocol (ECP) on patients in the intensive care unit (ICU). METHODS: This study utilized a randomized controlled design. Participants were patients who met the inclusion criteria and were admitted to the ICU (36 in the experimental group and 38 in the control group). The experimental group received an ECP, while the control group received standard eye care, starting the day after admission, for a duration of 10 days. The ECP classifies the degree of eyelid obstruction into three stages based on the degree of exposure to the lower eyelid conjunctiva and cornea. The protocol included cleansing with normal saline gauze, administering eye drops, applying silicone and polyurethane films, and recommending consultation with an ophthalmologist if necessary. The effectiveness of ECP was assessed by analyzing tear volume, hyperemia, chemosis, and eye discharge. Data analysis was conducted using SPSS 27.0, employing the Mann-Whitney U-test and generalized estimating equations. RESULTS: On day 5, the experimental group demonstrated a significant increase in tear volume in both eyes compared with the control group. However, no statistically significant differences were observed in the incidence of hyperemia, chemosis, and eye discharge on days 5 and 10 of the intervention. CONCLUSION: The application of the ECP in this study increased tear volume in ICU patients, thereby reducing discomfort caused by dry eyes. It has the potential to prevent complications such as damage to the surface of the eyeball resulting from decreased tear volume.

Beneficial Effects of Cocoa Flavanols on Microvascular Responses in Young Men May Be Dependent on Ethnicity and Lifestyle.

Cocoa flavan-3-ols affect endothelium-dependent responses in resistance vessels and microcirculation has received little attention. We tested the effects of dark chocolate consumption (396 mg total flavanols/day for 3 days) in two Groups of 10 men (18-25 years; non-smokers) each comprising equal numbers of White European (WE) and South Asian (SA) ethnicity. In Group 1, dark chocolate did not affect reactive hyperaemia in forearm muscle, but augmented muscle dilatation evoked by acute mental stress, and reactive hyperaemia and acetylcholine (ACh)-evoked dilatation in cutaneous microcirculation. Conversely, in Group 2, chocolate did not affect cutaneous reactive hyperaemia or ACh-evoked dilatation, but these responses were blunted in Group 1 relative to Group 2. Further, when Groups 1 and 2 were combined, responses were blunted in SAs relative to WEs, augmented by chocolate in SAs only. In Group 2 individuals whose ACh-evoked dilatation was attenuated by nitric oxide synthase (NOS) inhibition, ACh-evoked dilatation was not altered after chocolate, but the attenuating effect of NOS inhibition was lost. Conversely, in Group 2 individuals whose ACh-evoked dilatation was enhanced by NOS inhibition, ACh-evoked dilatation was also augmented by chocolate. We propose that in resistance and microvessels of young men, cocoa flavan-3-ols preferentially augment endothelium-dependent dilator responses whose responses are depressed by familial and lifestyle factors more prevalent in SAs than Wes. Flavan-3-ols may facilitate the NOS pathway but also influence other endothelium-dependent dilators.

Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.

Intracoronary ECG ST-segment shift remission time during reactive myocardial hyperemia: a new method to assess hemodynamic coronary stenosis severity.

Fractional flow reserve (FFR) measurements are recommended for assessing hemodynamic coronary stenosis severity. Intracoronary ECG (icECG) is easily obtainable and highly sensitive in detecting myocardial ischemia due to its close vicinity to the myocardium. We hypothesized that the remission time of myocardial ischemia on icECG after a controlled coronary occlusion accurately detects hemodynamically relevant coronary stenosis. This retrospective, observational study included patients with chronic coronary syndrome undergoing hemodynamic coronary stenosis assessment immediately following a strictly 1-min proximal coronary artery balloon occlusion with simultaneous icECG recording. icECG was used for a beat-to-beat analysis of the ST-segment shift during reactive hyperemia immediately following balloon deflation. The time from coronary balloon deflation until the ST-segment shift reached 37% of its maximum level, i.e., icECG ST-segment shift remission time (τ-icECG in seconds), was obtained by an automatic algorithm. τ-icECG was tested against the simultaneously obtained reactive hyperemia FFR at a threshold of 0.80 as a reference parameter. From 120 patients, 139 icECGs (age, 68 ± 10 yr old) were analyzed. Receiver operating characteristic (ROC) analysis of τ-icECG for the detection of hemodynamically relevant coronary stenosis at an FFR of ≤0.80 was performed. The area under the ROC curve was equal to 0.621 (P = 0.0363) at an optimal τ-icECG threshold of 8 s (sensitivity, 61%; specificity, 67%). τ-icECG correlated inversely and linearly with FFR (P = 0.0327). This first proof-of-concept study demonstrates that τ-icECG, a measure of icECG ST segment-shift remission after a 1-min coronary artery balloon occlusion accurately detects hemodynamically relevant coronary artery stenosis according to FFR at a threshold of ≥8 s.NEW & NOTEWORTHY Invasive hemodynamic measurements are recommended by the current cardiology guidelines to guide percutaneous coronary interventions in the setting of chronic coronary syndrome. However, those pressure-derived indices demonstrate several theoretical and practical limitations. Thus, this study demonstrates the accuracy of a novel, pathophysiology-driven approach using intracoronary ECG for the identification of hemodynamically relevant coronary lesions by quantitatively assessing myocardial ischemia remission.

Comparison of analysis strategies to assess sex differences in microvascular reperfusion using near-infrared spectroscopy.

The near-infrared spectroscopy (NIRS) vascular occlusion test (VOT) assesses microvascular reperfusion. Two strategies have been used to quantify reperfusion following reactive hyperemia, but it is unclear whether both yield similar results when comparing biological sex. This study aimed to determine whether sex differences in NIRS-based microvascular reperfusion are similarly apparent using the 10-s reactive hyperemia slope of the tissue saturation index (StO2) signal (slope 2) and the halftime to maximal reperfusion (T ½). Healthy, recreationally active males (n = 31) and females (n = 31) between 18 and 82 years took part in this study. A NIRS VOT was performed on the tibialis anterior muscle, and reperfusion was quantified using slope 2 (% s-1) and T ½ (s). Adipose tissue thickness (ATT) was higher in females (P = 0.009), which was associated with a lower StO2 (P = 0.001) and oxygenated hemoglobin (O2Hb) (P = 0.05) signal range. The StO2 slope 2 was significantly steeper in males versus females (P = 0.001) but not after correcting for ATT (P = 0.295). There were no sex differences in StO2 T ½ (P = 0.067) or O2Hb T ½ (P = 0.197). In a subset of males (n = 26) and females (n = 21) with similar ATT, there were no sex differences in StO2 slope 2 (P = 0.068), StO2 T ½ (P = 0.491), or O2Hb T ½ (P = 0.899). An ATT-corrected StO2 slope 2 or the T ½ approach is recommended for analysis of NIRS-based microvascular reperfusion when differences in ATT are present between sexes.NEW & NOTEWORTHY Sex differences in near-infrared spectroscopy (NIRS)-based microvascular reperfusion have been previously reported. We found that greater adipose tissue thickness in females reduces kinetic measures of NIRS-based microvascular reperfusion. Sex differences are eliminated when performing an adipose tissue thickness correction, when the NIRS signal range is accounted for, or when adipose tissue thickness is similar between sexes. This highlights the importance of considering factors that affect NIRS signals, such as adipose tissue thickness, when drawing comparisons between groups.

Changes in absolute coronary flow and microvascular resistance during exercise in patients with ANOCA.

BACKGROUND: Whether saline-induced hyperaemia captures exercise-induced coronary flow regulation remains unknown. AIMS: Through this study, we aimed to describe absolute coronary flow (Q) and microvascular resistance (Rµ) adaptation during exercise in participants with angina with non-obstructive coronary artery disease (ANOCA) and to explore the correlations between saline- and exercise-derived coronary flow reserve (CFR) and microvascular resistance reserve (MRR). METHODS: Rµ, Q, CFR and MRR were assessed in the left anterior descending artery using continuous thermodilution with saline infusion at 10 mL/min (rest), 20 mL/min (hyperaemia) and finally at a 10 mL/min infusion rate during stress testing with a dedicated supine cycling ergometer. An incremental workload of 30 watts every two minutes was applied. A saline-derived CFR (CFRsaline) cutoff <2.5 was used to identify coronary microvascular dysfunction (CMD). RESULTS: CFRsaline-defined CMD was observed in 53.3% of the participants (16/30). While cycling, these patients less of an ability to increase Q (7 [interquartile range [IQR] 30.5-103.0] vs 21 [IQR 5.8-45.0] mL/min/30 watts; p=0.01) due to a smaller decrease of Rµ (109 {IQR 32-286} vs 202 [IQR 102-379] Wood units [WU]/30 watts; p<0.01) as compared with the group with normal CFRsaline. In the overall population, CFRsaline and exercise-derived CFR (CFRexercise) were 2.70±0.90 and 2.85±1.54, respectively, with an agreement classification of 83.3%. A good correlation between saline and exercise techniques for both CFR (r=0.73; p<0.0001) and MRR (r=0.76; p<0.0001) was observed. Among participants with normal CFRsaline, 28.7% (4/14) had an impaired CFRexercise <2.5 at the peak of exercise due to a moderate and late decrease of Rµ. CONCLUSIONS: Saline-induced hyperaemia provided a valid surrogate for exercise physiology independently of the absolute level of CFR and MRR, although exercise provided more granularity to evaluate adaptation among participants with exercise-related CMD.

Association between optical coherence tomography-defined culprit morphologies and changes in hyperemic coronary flow after elective stenting assessed by transthoracic Doppler echocardiography.

BACKGROUND: Stress-transthoracic Doppler echocardiography (S-TDE) provides a noninvasive assessment of coronary flow parameters in the left anterior descending artery (LAD). However, the association between morphological characteristics and coronary flow changes after elective percutaneous coronary intervention (PCI) remains unclear. We aimed to evaluate the relationships between periprocedural coronary flow changes observed on S-TDE and lesion-specific plaque characteristics obtained by optical coherence tomography (OCT) in the interrogated vessels in patients with chronic coronary syndrome (CCS). METHODS AND RESULTS: Patients with CCS who underwent pre- and post-PCI S-TDE and elective fractional flow reserve (FFR)-guided PCI under OCT guidance for de novo single LAD lesions were included. S-TDE-derived hyperemic diastolic peak flow velocity (hDPV) was used as a surrogate for coronary flow. Lesions were categorized into two groups based on the %hDPV increase or decrease. The baseline clinical, physiological, and OCT findings were compared between the groups. In total, 103 LAD lesions were studied in 103 patients. After PCI, hDPV significantly increased from 55.6 cm/s to 69.5 cm/s (P<0.01), with a median %hDPV increase of 27.2 (6.32-59.1) %, while %hDPV decreased in 20 (19.4%) patients. The FFR improved in all patients. On OCT, layered plaques were more frequently present in the culprit vessels in the %hDPV-decrease group than in the %hDPV-increase group (85.0% vs. 50.6%, P = 0.01). Multivariable logistic regression analysis showed that the presence of layered plaques and high pre-PCI hDPV were independent predictors of %hDPV decrease. CONCLUSIONS: In patients who underwent successful uncomplicated elective PCI for de novo single LAD lesions, the presence of layered plaques was independently associated with hyperemic coronary flow decrease as assessed by S-TDE.

Acute effects of energy drink consumption on microvascular reactivity in young male volunteers at rest: a randomized trial.

Energy drinks are nonalcoholic beverages whose main ingredients are sugar, taurine, and caffeine. The consumption of energy drinks is increasing worldwide, but only a few conflicting studies have investigated the vascular effects of energy drinks in young adults. The aim of this study was to evaluate microvascular reactivity before and after energy drinks consumption in young healthy male volunteers. This was a cross-sectional prospective study. Microvascular reactivity signals were evaluated in the skin of the forearm using laser speckle contrast imaging with acetylcholine (ACh) iontophoresis before and 90 and 180 min after the randomized consumption of one ED or the same volume of water (control), followed by a postocclusive reactive hyperemia (PORH) test. Thirty-two volunteers were evaluated (age: 25.4±4.3 years). Energy drink consumption prevented the rest-induced reduction in cutaneous vascular conductance over time that was observed in the control group. In the control group, there were significant reductions in microvascular vasodilation at 90 and 180 min compared to baseline (P=0.004), but this was not the case in the energy drink group (P=0.76). Our results demonstrated that the reduction in microvascular conductance associated with prolonged immobility can be prevented by the consumption of one energy drink, highlighting the vasodilator effects of this beverage in young individuals at rest. The between-study variability in terms of the brand of energy drinks and the ingested volume, as well as the method of vascular evaluation and the inclusion criteria, may explain the discrepancies among previous studies on the vascular effects of energy drinks.

Development and validation of a novel angiography-derived index of absolute coronary blood flow and resistance.

Intracoronary continuous thermodilution has been recently proposed as an invasive method to quantify absolute coronary flow (Qabs) and resistance (Rabs) in vivo. The aim of the present study is to develop and validate of a novel pressure-wire- and microcatheter-free surrogate of coronary flow and resistance derived from a standard coronary angiogram. Angiography derived coronary flow (Qangio) and resistance (Rangio) was prospectively validated in a two-center cohort of patients from Oxford Heart Centre and the Essex Cardiothoracic Centre. Qabs and Rabs were measured during resting and hyperemic conditions with continuous thermodilution using the Rayflow microcatheter. Qangio and Rangio were computed from the diagnostic coronary angiogram in a blinded fashion in resting and hyperemic conditions. A total of 62 patients and 115 vessels were included in the present analysis. The median Qabs at rest was 75 ml/min (53-95) and 151 ml/min (105-203) during hyperemia; Qangio at rest was 84 ml/min (66-108) and 154 ml/min (115-195) during hyperemia. There was a strong correlation between Qabs and Qangio (R = 0,72; p < 0.001, R = 0,86; p < 0.001 respectively) with satisfactory interclass correlation (0.841, 95% CI 0.509-0.957; p = 0.0003). The median Rabs was 1111 mmHg/(L/min) (830-1581.4) at rest and 454 mmHg/(L/min) (348-610) during hyperemia; angiographic resistance (Rangio) was 937.4 mmHg/(L/min) (695.4-1261.9) at rest and 492.4 mmHg/(L/min) (406-697) during hyperemia. There was a strong correlation between Rabs and Rangio in both conditions (R = 0,81; p < 0.001 and R = 0,78; p < 0.001 respectively). The was a good correlation between absolute coronary flow reserve (CFR) and angiography-derived CFR (R = 0,61; p < 0.001) and between absolute microvascular resistance reserve (MRR) and angiography-derived MRR (R = 0,49; p < 0.001).

Statin therapy improves locomotor muscle microvascular reactivity in patients with heart failure with preserved ejection fraction.

Peripheral microvascular dysfunction has been documented in patients with heart failure with preserved ejection fraction (HFpEF), which may be related to elevated levels of inflammation and oxidative stress. Unfortunately, few strategies have been identified to effectively ameliorate this disease-related derangement. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on lower limb microvascular reactivity, functional capacity, and biomarkers of inflammation and oxidative stress in patients with HFpEF (statin, n = 8, 76 ± 6 yr; placebo, n = 8, 68 ± 9 yr). The passive limb movement (PLM)-induced hyperemic response and 6-min walk test (6MWT) distance were evaluated to assess ambulatory muscle microvascular function and functional capacity, respectively. Circulating biomarkers were also measured to assess the contribution of changes in inflammation and redox balance to these outcomes. The total hyperemic response to PLM, assessed as leg blood flow area under the curve (LBFAUC), increased following the statin intervention (pre, 60 ± 68 mL; post, 164 ± 90 mL; P < 0.01), whereas these variables were unchanged in the placebo group (P = 0.99). There were no significant differences in 6MWT distance following statin or placebo intervention. Malondialdehyde (MDA), a marker of lipid peroxidation, was significantly reduced following the statin intervention (pre, 0.68 ± 0.10; post, 0.51 ± 0.11; P < 0.01) while other circulating biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to a diminution in oxidative stress.NEW & NOTEWORTHY This was the first study to investigate the impact of statin administration on locomotor muscle microvascular function in patients with HFpEF. In support of our hypothesis, the total hyperemic response to PLM, assessed as leg blood flow area under the curve, increased, and malondialdehyde, a marker of oxidative damage, was reduced following the statin intervention. Together, these data provide new evidence for the efficacy of statin administration to improve locomotor muscle microvascular reactivity in patients with HFpEF, which may be due, in part, to reduced oxidative stress.

Cerebral blood flow in relation to peripheral endothelial function in youth bipolar disorder.

INTRODUCTION: Anomalous cerebral blood flow (CBF) is evident in bipolar disorder (BD), however the extent to which CBF reflects peripheral vascular function in BD is unknown. This study investigated endothelial function, an index of early atherosclerosis and cardiovascular disease risk, in relation to CBF among youth with BD. METHODS: Participants included 113 youth, 13-20 years old (66 BD; 47 healthy controls [HC]). CBF was measured using arterial spin labeling with 3T MRI. Region of interest analyses (ROI; global grey matter, middle frontal gyrus, anterior cingulate cortex, temporal cortex, caudate) were undertaken alongside voxel-wise analyses. Reactive hyperemia index (RHI), a measure of endothelial function, was assessed non-invasively via pulse amplitude tonometry. General linear models were used to examine RHI and RHI-by-diagnosis associations with CBF, controlling for age, sex, and body mass index. Bonferroni correction for multiple comparisons was used for ROI analyses, such that the significance level was divided by the number of ROIs (α = 0.05/5 = 0.01). Cluster-extent thresholding was used to correct for multiple comparisons for voxel-wise analyses. RESULTS: ROI findings were not significant after correction. Voxel-wise analyses found that higher RHI was associated with lower left thalamus CBF in the whole group (p < 0.001). Additionally, significant RHI-by-diagnosis associations with CBF were found in three clusters: left intracalcarine cortex (p < 0.001), left thalamus (p < 0.001), and right frontal pole (p = 0.006). Post-hoc analyses showed that in each cluster, higher RHI was associated with lower CBF in BD, but higher CBF in HC. CONCLUSION: We found that RHI was differentially associated with CBF in youth with BD versus HC. The unanticipated association of higher RHI with lower CBF in BD could potentially reflect a compensatory mechanism. Future research, including prospective studies and experimental designs are warranted to build on the current findings.