Laser Doppler Perfusion Monitoring Research Articles

ENDOTHELIAL-DEPENDENT VASCULAR REACTIVITY AFTER CARDIOPULMONARY BYPASS IS ASSOCIATED WITH UNIQUE METABOLOMIC SIGNATURES.

Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. Globally, we found 2,404 unique features in the plasma of patients undergoing CPB. Metabolites related to arginine biosynthesis were the most altered by CPB. Correlation of metabolic profiles with endothelial-dependent (acetylcholine [ACh]) or endothelial-independent (sodium nitroprusside [SNP]) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.

Characteristics of Inflammatory and Normal Endothelial Exosomes on Endothelial Function and the Development of Hypertension.

Endothelial dysfunction is associated with the development of hypertension. We hypothesize that inflammatory and normal endothelial exosomes play their roles by mediating endothelial function, and they induce endothelial angiogenesis through different signaling pathways. Endothelial cell-derived exosomes were isolated from the human umbilical vein endothelial cells (HUVECs) treated with (TExo) or without (CExo) tumor necrosis factor (TNF)-α. We monitored dermal microcirculation profiles in spontaneously hypertensive rats (SHRs) and WKY rats using a laser Doppler imager and a laser Doppler perfusion and temperature monitor. Tube formation, levels of angiogenesis-related proteins in HUVEC-conditioned media, and reactive oxygen species (ROS) levels were assessed following TNF-α, CExo, or TExo treatments. Western blot analysis was conducted to examine signaling proteins associated with inflammation and ROS. The results showed increased blood perfusion and the mean amplitude of endothelial oscillator in SHRs following CExo administration. TNF-α, CExo, and TExo treatments promoted endothelial tube formation and elevated levels of angiogenic factors and ROS. TExo significantly increased phosphorylation levels of STAT3, p38, and level of NF-κB, while decreasing phosphorylation levels of JNK and Erk (P < 0.01 or P < 0.05). CExo significantly increased STAT3 phosphorylation and reduced JNK and Erk phosphorylation (all P < 0.01). In conclusion, TNF-α and TExo induce inflammatory and pathological angiogenesis via the NF-κB pathway, while CExo exhibits a physiologically pro-angiogenic effect on endothelial cells. Increased ROS, interplaying with inflammatory signals, contribute to exosome-mediated alterations of endothelial function, thereby playing a role in the development of hypertension.

Evaluating the biomechanics of an in-between posture to create a multi-posture office environment.

Prolonged sitting during work is common and has been shown to cause health issues. However, changing working postures has been reported to reduce musculoskeletal issues and impact other health issues; thus, there is a need for an office environment with multiple choices of working postures. The purpose of this study was to evaluate changes in body position, body loading, and blood perfusion while in a seated, standing, and new office seating position, termed the in-between position. Ground reaction forces, joint angles, pelvic tilt, openness angle (angle between the pelvis plane and thorax), and blood perfusion were evaluated for three positions. A motion capture system with markers was used to capture the position of anatomical landmarks. A six-axis force plate was used to collect the ground reaction forces, and a laser doppler perfusion monitor was used to obtain the blood perfusion. Data showed that the in-between position articulated the hips, which provided a hip and lumbar position closer to a standing posture than a seated posture. The average vertical ground reaction force in the in-between position was larger than the seated position but significantly smaller than during standing (p < 0.0001). There were no significant differences in anterior/posterior ground reaction forces between the seated and the in-between positions (p = 0.4934). Lastly, blood perfusion increased during the dynamic transitions between positions indicating changes in blood flow. The in-between position provides benefits of both standing (larger pelvic tilt and increased lumbar lordosis) and sitting (reduction in ground reaction forces).

Long-term assessment of systemic microcirculatory function and plasma cytokines after coronavirus disease 2019 (COVID-19)

Systemic microvascular dysfunction has been shown to be present in COVID-19, and serum cytokines are known to be involved in the regulation of vascular function. We sought to evaluate systemic microvascular endothelial function, with laser doppler perfusion monitoring (LDPM), and plasma levels of cytokines after acute COVID-19. Individuals admitted to a Cardiology hospital with acute COVID-19 and followed for 12–15 months after recovery underwent noninvasive evaluation of systemic endothelium-dependent microvascular reactivity by cutaneous LDPM with local thermal hyperemia (LTH). A multiplex biometric immunoassay panel was used to assess 48 serum cytokines and chemokines. Twenty patients and 14 control volunteers were enrolled. The areas under the curves of vasodilation induced by LTH were significantly increased after recovery (P=0.009) and were not different from values obtained in healthy volunteers (P = 0.85). The peak microvascular flow during LTH did also significantly increase (P = 0.02), and was not different form values obtained in healthy volunteers (P = 0.55). Several cytokines displayed significantly reduced serum concentrations after recovery from COVID-19. In conclusion, endothelium-dependent systemic microvascular reactivity improved after recovery from COVID-19 in patients with cardiovascular diseases, in parallel with a reduction in the levels of several serum cytokines and chemokines involved in the regulation of vascular function and inflammation.

Optimizing atrio-ventricular delay in pacemakers using potentially implantable physiological biomarkers.

BackgroundHemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat‐by‐beat blood pressure (BP) measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices.We assess whether laser Doppler can be used instead of BP to optimize AV delay.MethodsFifty eight patients underwent 94 AV delay optimizations with biventricular or His‐bundle pacing using laser Doppler and simultaneous noninvasive beat‐by‐beat BP. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40–320 ms), with automatic quality control checking precision of the optimum.Five subsequent patients underwent an extended protocol to test the impact of greater numbers of alternations on optimization quality.Results55/94 optimizations passed quality control resulting in an optimal AV delay on laser Doppler similar to that derived by BP (median absolute deviation 12 ms).An extended protocol with increasing number of replicates consistently improved quality and reduced disagreement between laser Doppler and BP optima. With only five replicates, no optimization passed quality control, and the median absolute deviation would be 29 ms. These improved progressively until at 50 replicates, all optimizations passed quality control and the median absolute deviation was only 13 ms.ConclusionsLaser Doppler perfusion produces hemodynamic optima equivalent to BP. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

Endothelial-Dependent Responses Correlate with Pediatric SOFA Scores During Severe Sepsis and Septic Shock.

Sepsis is an exaggerated host response to an infectious challenge that is associated with significant alterations in vasomotor tone. We hypothesized that the endothelial dysfunction observed during severe sepsis and septic shock would correlate with the degree of organ failure as determined by the pediatric Sequential Organ Failure Assessment (pSOFA) score. Utilizing laser Doppler perfusion monitoring coupled with iontophoresis, we found that endothelium-dependent vascular reactivity to acetylcholine (ACh) stimulation significantly correlated with both total pSOFA scores and, more specifically, cardiovascular (CV) pSOFA scores. Alternatively, endothelium-independent vascular reactivity using sodium nitroprusside (SNP) did not demonstrate a significant relationship with pSOFA scores. These data suggest that endothelial-mediated vasculopathy may be a key driver of organ dysfunction during episodes of pediatric sepsis.

A Method for Accurately Optimizing Pacemaker Atrio-Ventricular Delay Timing Utilizing Potentially Implantable Physiological Biomarkers

Background: Hemodynamically optimal atrioventricular (AV) delay can be derived by echocardiography or beat-by-beat blood pressure measurements, but analysis is labor intensive. Laser Doppler perfusion monitoring measures blood flow and can be incorporated into future implantable cardiac devices. Objective: To assess whether laser Doppler can be used instead of blood pressure to optimize AV delay. Methods: 58 patients underwent 94 AV delay optimizations using laser Doppler and simultaneous non-invasive beat-by-beat blood pressure. Optimal AV delay was defined using a curve of hemodynamic response to switching from AAI (reference state) to DDD (test state) at several AV delays (40, 80, 120, 160, 200, 240 ms), with automatic quality control checking precision of the optimum. Five subsequent patients underwent an extended protocol to test the ability of greater numbers of alternations to improve optimization quality. Results: 55/94 optimizations passed quality control: optimal AV delay on laser Doppler was similar to that derived by blood pressure (median absolute deviation 12ms).The extended protocol showed that increasing the number of replicates consistently increased quality and reduced disagreement between laser Doppler and blood pressure optima. With only 5 replicates, no optimization passed quality control, and median absolute deviation would be 29ms. These improved progressively until at 50 replicates, all optimizations passed quality control and median absolute deviation was only 13ms. Conclusions: Laser Doppler perfusion produces hemodynamic optima equivalent to blood pressure. Quality control can be automatic. Adding more replicates, consistently improves quality. Future implantable devices could use such methods to dynamically and reliably optimize AV delays.

A method for accurately and dynamically optimising pacemaker atrio-ventricular delay timing using implantable physiological biomarkers

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): BRAVO trial: BHF SP/10/002/28189, FS/10/038, FS/11/92/29122, FS/13/44/30291) National Institute for Health Research Imperial Biomedical Research Centre. HOPE-HF trial: British Heart Foundation (CS/15/3/31405, FS/13/44/30291, FS/15/53/31615, FS/14/27/30752, FS/10/038). Introduction The optimal atrioventricular (AV) delay for implantable cardiac devices can be derived by echocardiography or beat-by-beat blood pressure measurements. However, both of these approaches are labour intensive and neither could be incorporated into an implantable cardiac device for frequent repeated optimisations. Laser Doppler perfusion monitoring (LDPM) measures blood flow through tissue. LDPM has been miniaturised ready to be incorporated into future implantable cardiac devices. Purpose We studied if LDPM is a clinically reliable alternative method to blood-pressure measurements to determine optimal AV delay. Methods Data from 58 patients undergoing 94 clinical AVD optimisations using LDPM and simultaneous non-invasive beat-by-beat blood pressure was obtained. The optimal AV delay for each method and for each optimisation was determined using a curve of haemodynamic response to switching from AAI (reference state) to DDD (test state) at a series of AV delays (40, 80, 120, 160, 200, 240 ms). We then compared the derived optimal AV delays between the two measurement approaches. We also assessed the impact of the paced heart-rate on agreement between laser Doppler and Blood-Pressure derived optimal AV delays. Results The AV delay derived using LDPM was not clinically significant different from that derived by blood pressure changes. The median difference was -9ms (IQR -26 to 7, p = 0.05). Variability between the two methods was low (median absolute deviation 17ms). Optimisations performed at higher heart-rates resulted in a non-significant smaller difference between the LDPM and blood-pressure derived AV delays (median absolute deviation 12 vs 22 ms, p = 0.11). Conclusions Optimal AVDs derived from non-invasive blood-pressure or laser Doppler perfusion methods are clinically equivalent. The addition of laser Doppler to future implantable cardiac devices may enable devices to dynamically and reliably optimise AV delays. Abstract Figure 1

Laser doppler derived peripheral perfusion can distinguish haemodynamically tolerated VT from haemodynamically compromised VT

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): NIHR Imperial Biomedical Research Centre Introduction Implantable Cardioverter-Defibrillators (ICDs) cannot distinguish between ventricular tachycardia (VT) with haemodynamic compromise from haemodynamically tolerated VT to ensure that therapies are delivered only when necessary. Currently, unnecessary therapies are reduced by longer duration thresholds and higher rate thresholds. This can result in ICDs withholding or delaying therapies during haemodynamically compromising VT while potentially still providing therapies during rapid or prolonged VT that is haemodynamically well tolerated. Laser doppler perfusion monitoring (LDPM) allows assessment of peripheral blood flow as a surrogate for haemodynamic status. We have previously demonstrated that laser doppler perfusion signals, analysed using an electro-mechanical coupling algorithm (SafeShock), can reliably identify loss of perfusion during ventricular fibrillation (VF), as well as discriminate VF from simulated lead fractures and T wave over-sensing. The utility of LDPM signals in VT, however, has not been established. Purpose In this study we assessed the utility of LDPM using the SafeShock algorithm to discriminate haemodynamically tolerated VT from VT with haemodynamic compromise. Methods Recruited participants underwent a rapid ventricular pacing protocol to simulate VT at different rates. Pacing was performed using the right ventricular lead of an implanted pacing device or a temporary pacing wire in the right ventricular apex. 3-lead ECG, blood pressure (either invasively using a radial artery catheter or non-invasively using beat-by-beat finometry) and LDPM signal were continuously recorded during the protocol. LDPM signals during simulated VT were analysed using the SafeShock electro-mechanical algorithm and compared to blood pressure change from baseline intrinsic rhythm to simulated VT. Results We obtained 588 recordings of simulated VT in 56 patients at rates of 100 bpm, 120 bpm, 140 bpm, 160 bpm, 180 bpm and 200 bpm. Percentage change in systolic blood pressure from baseline to VT correlated with LDPM-derived perfusion value during VT (Spearman’s Rho = 0.7786, p &amp;lt; 0.0001). Using a cut-off of 5 units, perfusion value predicted a 20% drop in systolic blood pressure in VT with an accuracy of 89.4% (sensitivity 94.8%, specificity 83.6%, p value &amp;lt;0.0001). Conclusions Peripheral perfusion measurements, analysed using an electro-mechanical algorithm, can accurately discriminate haemodynamically tolerated VT from VT with haemodynamic compromise. ICDs with integrated LDPM sensors and algorithms could make therapy decisions based on the circulatory status of patients with arrhythmias not just rate and duration parameters. This could reduce unnecessary therapies while facilitating prompt treatment of compromising arrhythmias. Abstract Figure 1

The Inverse Relationship Between Endothelium-Dependent Vasodilation and Blood Pressure is Lost After Cardiopulmonary Bypass.

Cardiopulmonary bypass (CPB) is required for the surgical correction of congenital heart defects and incites an acute inflammatory response that impairs endothelial function post-operatively. Therefore, we hypothesized that the pre-operative relationship between endothelial function and blood pressure would be impaired after CPB-mediated inflammation. Using laser Doppler perfusion monitoring coupled with iontophoresis, we found that while there was a significant inverse correlation between endothelium-dependent vascular reactivity to acetylcholine (ACh) stimulation and systolic blood pressure (SBP), this relationship was lost after CPB. No relationship was observed between endothelium-independent vascular reactivity using sodium nitroprusside (SNP) and SBP either pre-CPB or any point thereafter. Additionally, neither CPB time nor inflammatory cytokines correlated with the degree of responsiveness to ACh. These data suggest that the measurement of endothelium impairment after CPB may be more reflective of cardiovascular health than SBP alone.

Systemic microvascular endothelial dysfunction and disease severity in COVID-19 patients: Evaluation by laser Doppler perfusion monitoring and cytokine/chemokine analysis

BackgroundMicrovascular dysfunction, serum cytokines and chemokines may play important roles in pathophysiology of coronavirus disease 2019 (COVID-19), especially in severe cases. MethodsPatients with COVID-19 underwent non-invasive evaluation of systemic endothelium-dependent microvascular reactivity - using laser Doppler perfusion monitoring in the skin of the forearm - coupled to local thermal hyperemia. Maximal microvascular vasodilatation (44 °C thermal plateau phase) was used as endpoint. A multiplex biometric immunoassay was used to assess a panel of 48 serum cytokines and chemokines. Severe COVID-19 (S-COVID) was defined according to WHO criteria, while all other cases of COVID-19 were considered mild to moderate (M-COVID). A group of healthy individuals who tested negative for SARS-CoV-2 served as a control group and was also evaluated with LDPM. ResultsThirty-two patients with COVID-19 (25% S-COVID) and 14 controls were included. Basal microvascular flow was similar between M-COVID and controls (P = 0.69) but was higher in S-COVID than in controls (P = 0.005) and M-COVID patients (P = 0.01). The peak microvascular vasodilator response was markedly decreased in both patient groups (M-COVID, P = 0.001; S-COVID, P < 0.0001) compared to the healthy group. The percent increases in microvascular flow were markedly reduced in both patient groups (M-COVID, P < 0.0001; S-COVID, P < 0.0001) compared to controls. Patients with S-COVID had markedly higher concentrations of dissimilar proinflammatory cytokines and chemokines, compared to patients with M-COVID. ConclusionsIn patients with COVID-19, especially with S-COVID, endothelium-dependent microvascular vasodilator responses are reduced, while serum cytokines and chemokines involved in the regulation of vascular function and inflammation are increased.

Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass.

Cardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Single-center prospective observational cohort pilot study. Pediatric cardiac ICU at a tertiary children's hospital. Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. None. Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008). Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.

Effects of Vasopressors on Circulation of Porcine Abdominal Island Flap Model

OBJECTIVES: During reconstructive surgical procedures, systemic vasopressors are frequently used to maintain normal blood pressure. However, questions have arisen regarding the pharmacologic effects of vasopressors on flap circulation. Many plastic surgeons have expressed concern about the possibility of impaired flap circulation caused by the vasoconstrictive effect of the drugs. However, the opposing argument exists that the increase of mean arterial pressure from vasoactive agents may improve flap perfusion. The purpose of this study was to evaluate the effect of commonly used vasopressors on flap circulation. MATERIALS AND METHODS: The vertical rectus abdominis myocutaneous island flap was raised in 5 female pigs (38.2~40.7 kg). Hemodynamic parameters were measured continuously by carotid arterial catheter. A bidirectional transonic vascular Doppler flow probe and laser Doppler perfusion monitor unit were applied to record the continuous change of pedicle artery flow and microvascular perfusion following intravenous administration of dopamine (3, 5, 10 μg/kg/min), dobutamine (1.25, 2.5, 5 μg/kg/min), and norepinephrine (0.05, 0.1, 0.2 μg/kg/min). RESULTS: Both microvascular perfusion and pedicle flow were generally proportional to mean arterial pressure, and all the 3 vasopressors improved flap perfusion and pedicle flow without deleterious effect. Norepinephrine showed that the highest microvascular perfusion and dobutamine showed the highest pedicle flow rate. Mean blood pressure was the only statistically significant factor that affects both microvascular perfusion and pedicle flow (P < 0.0001). CONCLUSIONS: Our results strongly suggest that the foremost 3 vasopressors can be used for flap surgery without deterioration, and maintaining adequate systemic blood pressure is crucial for good flap circulation.

Ischemic Preconditioning and Iloprost Reduces Ischemia-Reperfusion Injury in Jejunal Flaps: An Animal Model.

Free jejunal flaps are among the most commonly used flaps for esophageal reconstruction. However, ischemia-reperfusion injury caused by warm ischemia seen during transfer limits their use. Iloprost, a prostacyclin analogue, has been shown to reduce ischemia-reperfusion injury in various organs. The authors investigated tissue damage in jejunal flaps with iloprost and ischemic preconditioning and compared the effectiveness of these two modalities. Thirty-four Sprague-Dawley rats were randomized into five groups: sham, ischemia-reperfusion (control), ischemic preconditioning, iloprost, and ischemic preconditioning plus iloprost. All flaps, except those in the sham group, underwent ischemia for 60 minutes and reperfusion for 2 hours. Flap perfusion was assessed by laser Doppler perfusion monitoring. Histologic sections were scored using the Chiu scoring system. Superoxide dismutase and myeloperoxidase levels were measured spectrophotometrically. Animals that were administered iloprost and/or underwent ischemic preconditioning had better postischemic recovery of mesenteric perfusion (ischemic preconditioning, 78 percent; iloprost, 83 percent; ischemic preconditioning plus iloprost, 90 percent; versus ischemia-reperfusion, 50 percent; p < 0.05). All intervention groups showed improved histology of jejunal flaps following ischemia-reperfusion injury (ischemic preconditioning, 3; iloprost, 2.3; ischemic preconditioning plus iloprost, 3.2; versus ischemia-reperfusion, 4.7; p < 0.01, p < 0.001, and p < 0.05, respectively). Superoxide dismutase levels were higher in ischemic preconditioning, iloprost plus ischemic preconditioning, and iloprost groups (ischemic preconditioning, 2.7 ± 0.2; ischemic preconditioning plus iloprost, 2.5 ± 0.3; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.01; iloprost, 2.4 ± 1.1; versus ischemia-reperfusion, 1.2 ± 0.1; p < 0.05). Myeloperoxidase, a marker for neutrophil infiltration, was lower in the iloprost group (iloprost, 222 ± 5; versus ischemia-reperfusion, 291 ± 25; p < 0.05). This study showed that both iloprost and ischemic preconditioning reduced reperfusion injury in jejunal flaps. Based on histologic results, iloprost may be a novel treatment alternative to ischemic preconditioning.

Effects of vasopressors on circulation in the porcine abdominal island flap model

During reconstructive surgical procedures, systemic vasopressors are frequently used to maintain normal blood pressure. However, questions have arisen regarding the pharmacologic effects of vasopressors on flap circulation. Many plastic surgeons have expressed concern about the possibility of impaired flap circulation caused by the vasoconstrictive effect of the drugs. However, the opposing argument exists that the increase in mean arterial pressure from vasoactive agents may improve flap perfusion. The purpose of this study was to evaluate the effect of commonly used vasopressors on flap circulation. The vertical rectus abdominis myocutaneous (VRAM) island flap was raised in five female pigs (38.2∼40.7 kg). Hemodynamic parameters were measured continuously by a carotid arterial catheter. A bi-directional transonic vascular doppler flow probe and Laser Doppler perfusion monitor (LDPM) unit were applied to record the continuous change in pedicle artery flow and microvascular perfusion following intravenous administration of dopamine (3, 5, 10µg/kg/minute), dobutamine (1.25, 2.5, 5µg/kg/minute), and norepinephrine (0.05, 0.1, 0.2µg/kg/minute). Both microvascular perfusion and pedicle flow were generally proportional to the mean arterial pressure, and all three vasopressors improved flap perfusion and pedicle flow without deleterious effects. Norepinephrine showed the highest microvascular perfusion and dobutamine showed the highest pedicle flow rate. The mean blood pressure was the only statistically significant factor to affect both microvascular perfusion and pedicle flow (p<0.0001). Our results strongly suggest that the foremost three vasopressors can be used for flap surgery without deterioration, and that the maintenance of adequate systemic blood pressure is crucial for good flap circulation.

Anti-Migraine Effect of the Herbal Combination of Chuanxiong Rhizoma and Cyperi Rhizoma and UPLC-MS/MS Method for the Simultaneous Quantification of the Active Constituents in Rat Serum and Cerebral Cortex.

Chuanxiong Rhizoma and Cyperi Rhizoma (CRCR), an ancient and classic formula comprised of Chuanxiong Rhizoma and Cyperi Rhizoma in a weight ratio of 1:2, has long been used for curing migraine. This study aimed to explore their anti-migraine effect and active constituents. A nitroglycerin (NTG)-induced migraine model in rats was established to evaluate pharmacological effects. Cerebral blood flow was detected by a laser Doppler perfusion monitor. The levels of endothelin-1 (ET-1), γ-aminobutyric acid (GABA), nitric oxide synthase (NOS), nitric oxide (NO), 5-hydroxytryptamine (5-HT), 5-hydoxyindoleacetic acid (5-HIAA), calcitonin gene-related peptide (CGRP) and β-endorphin (β-EP) were quantified with enzyme-linked immunosorbent assay. CGRP and c-Fos mRNA expression were quantified with quantitative real-time polymerase chain reaction. A UPLC-MS/MS method was developed and validated for the simultaneous quantification of active constituents in rat serum and cerebral cortex. CRCR significantly increased cerebral blood flow, decreased the levels of ET-1, GABA and NOS, and increased the levels of 5-HT, 5-HIAA and β-EP in NTG-induced migraine rats. CGRP levels and CGRP mRNA expression, as well as c-Fos mRNA expression in the brainstem were markedly down-regulated with the treatment of CRCR. After oral administration of CRCR, ferulic acid (FA), senkyunolide A (SA), 3-n-butylphthalide (NBP), Z-ligustilide (LIG), Z-3-butylidenephthalide (BDPH), cyperotundone (CYT), nookatone (NKT) and α-cyperone (CYP) were qualified in rat serum and cerebral cortex. The above results suggested that CRCR showed powerfully therapeutic effects on migraine via increasing the cerebral blood flow, decreasing the expression of CGRP and c-Fos mRNA, and regulating the releasing of ET-1, GABA, NOS, 5-HT, 5-HIAA, CGRP and β-EP in the serum and brainstem, consequently relieving neurogenic inflammation. The active constituents in CRCR for treating migraine were FA, SA, NBP, LIG, BDPH, CYT, NKT and CYP. These findings contributed for the further use of CRCR as a combinational and complementary phytomedicine for migraine treatment.

Development of a Function-Integrative Sleeve for Medical Applications.

Function-integrative textiles bear the potential for a variety of applications in the medical field. Recent clinical investigations suggest that the application of a function-integrative fabric could have a positive impact on currently applied diagnostic procedures of a specific type of tumour. In this context, the fabric should enable local warming of a patient’s upper extremity as well as blood flow measurement. Existing solutions comprise a warming system but lack a measuring apparatus for blood flow determination. With regard to the quality of results of current diagnostic procedures, the local warming of the patients’ upper extremity and the simultaneous determination of the blood flow plateau are crucial. In the present paper, the development process of a function-integrative sleeve is introduced. Besides the development of an adaptable sleeve-design, the manufacturing process of an integrated warming system was also addressed. Furthermore, the identification of crucial physiological effects, using a Laser Doppler Perfusion Monitor, is introduced. During testing of the function-integrative sleeve, modulation of the desired physiological effects was observed. The results support the initial assumptions and dictate further investigations on increasing user-friendliness and cost-efficiency during adjusting and determining the physiological effects in the course of tumour diagnosis.

Cutaneous perfusion of the human lactating breast: a pilot study with laser Doppler perfusion monitoring

Objective: Knowledge on the hemodynamics of the human lactating breast contributes to our understanding of lactation physiology, as well as the development and management of breastfeeding problems. The objective of this pilot study was to investigate whether laser Doppler perfusion monitoring (LDPM) can be employed to measure physiological changes in mammary cutaneous perfusion during milk extraction. Approach: We evaluated mammary cutaneous perfusion with LDPM in nine lactating women during milk extraction in both the ipsilateral (‘milk extracting’) and contralateral (‘passive’) breast. Fourier domain filtering of the LDPM signal was applied to correct for the influence of the periodic tissue movement caused by the breast pump. Main results: Cutaneous perfusion increased temporary during 23.7 ± 18.9 s by 18%–74% for all women who sensed their milk ejection reflex (n = 6) in both the ipsilateral and contralateral breast. For those women who did not sense a milk ejection reflex (n = 3), the changes in cutaneous perfusion were less outspoken (maximally 26%). Significance: This pilot study provides new insights into mammary hemodynamics and demonstrates that LDPM is a promising method for the further investigation of physiological changes in mammary cutaneous perfusion during milk ejection. Objective feedback on the occurrence and progression of milk ejection can support lactation research in general, maternal breastfeeding confidence, and may be an early indicator for the development of breastfeeding problems.

Quantification of Electromechanical Coupling to Prevent Inappropriate Implantable Cardioverter-Defibrillator Shocks.

ObjectivesThis study sought to test specialized processing of laser Doppler signals for discriminating ventricular fibrillation (VF) from common causes of inappropriate therapies.BackgroundInappropriate implantable cardioverter-defibrillator (ICD) therapies remain a clinically important problem associated with morbidity and mortality. Tissue perfusion biomarkers, implemented to assist automated diagnosis of VF, sometimes mistake artifacts and random noise for perfusion, which could lead to shocks being inappropriately withheld.MethodsThe study tested a novel processing algorithm that combines electrogram data and laser Doppler perfusion monitoring as a method for assessing circulatory status. Fifty patients undergoing VF induction during ICD implantation were recruited. Noninvasive laser Doppler and continuous electrograms were recorded during both sinus rhythm and VF. Two additional scenarios that might have led to inappropriate shocks were simulated for each patient: ventricular lead fracture and T-wave oversensing. The laser Doppler was analyzed using 3 methods for reducing noise: 1) running mean; 2) oscillatory height; and 3) a novel quantification of electromechanical coupling which gates laser Doppler relative to electrograms. In addition, the algorithm was tested during exercise-induced sinus tachycardia.ResultsOnly the electromechanical coupling algorithm found a clear perfusion cut off between sinus rhythm and VF (sensitivity and specificity of 100%). Sensitivity and specificity remained at 100% during simulated lead fracture and electrogram oversensing. (Area under the curve running mean: 0.91; oscillatory height: 0.86; electromechanical coupling: 1.00). Sinus tachycardia did not cause false positive results.ConclusionsQuantifying the coupling between electrical and perfusion signals increases reliability of discrimination between VF and artifacts that ICDs may interpret as VF. Incorporating such methods into future ICDs may safely permit reductions of inappropriate shocks.

Microvascular endothelial dysfunction during cardiopulmonary bypass in surgery for correction of cyanotic and acyanotic congenital heart disease

ObjectiveTo evaluate endothelium-dependent microvascular reactivity during cardiopulmonary bypass (CPB) in surgery for the correction of cyanotic and acyanotic congenital heart disease (CHD) in children and infants using laser Doppler perfusion monitoring (LDPM). MethodsThis cross-sectional observational study included one hundred consecutive acyanotic (AC, n = 61) and cyanotic (C, n = 39) pediatric patients scheduled for cardiac surgery for correction of CHD. The endothelium-dependent microvascular vasodilation of the skin of the forehead was evaluated using a single-point LDPM coupled with local thermal hyperemia (LTH). ResultsLTH induced significant increases in microvascular conductance both in AC and C patients after the induction of anesthesia, during CPB and after weaning from CPB. Nevertheless, the vasodilation induced by LTH was significantly blunted during CPB when compared with values obtained after the induction of anesthesia both in AC and C patients. Microvascular endothelial reactivity nearly normalized after the discontinuation of CPB. ConclusionThe evaluation of systemic microvascular reactivity on the forehead skin of infants and children using LDPM appears to be a valuable tool for optimizing microvascular perfusion during CPB in pediatric cardiac surgery.