Microcirculatory Response Research Articles

Neuro- and vasoprotective potential of neuropeptide Y Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats

Numerous in vitro and in vivo experimental studies indicate that neuropeptide Y Y2 receptors (Y2R) are potential targets for neuroprotective therapy, including neuroprotection against ischemic stroke in healthy rats. Since stroke in humans is typically associated with comorbidities and long-term hypertension is the most common comorbidity leading to stroke, this study aimed to assess the neuroprotective potential of the Y2R agonist NPY13–36 in the rats with essential hypertension (SHR) subjected to 90 min middle cerebral artery suture occlusion with subsequent reperfusion (MCAOR). The cerebrocortical microflow in the ischemic focus and penumbra was continuously monitored with a Laser-Doppler flowmeter. NPY13–36 (10 μg/6 μl physiological saline solution) was administered intracerebroventricularly (i.c.v.) during ischemia or early reperfusion. The infarct area (triphenyltetrazolium chloride staining), behavioral tests (gait, mobility, and sensorimotor functions), and the response of the cerebrocortical microcirculation in the penumbra to hypercapnia and to the inhibition of the synthesis of nitric oxide were studied. Our results demonstrate that administration of NPY13-36 reduces the size of the infarct, improves motor functions, and restores microcirculatory response to the blockade of nitric oxide synthase when administered during reperfusion. The novelty of this study is a finding of the vasoprotective effect of NPY13-36 in brain ischemia/reperfusion. Moreover, this study provides evidence of the beneficial effects of NPY13-36 in animals with essential hypertension and indicates that Y2R ligands may be promising candidates for treating the ischemic brain in the case of this disease.

Assessment of Microvascular Function Based on Flowmotion Monitored by the Flow-Mediated Skin Fluorescence Technique.

This review summarizes studies dedicated to the assessment of microvascular function based on microcirculatory oscillations monitored by the Flow-Mediated Skin Fluorescence (FMSF) technique. Two approaches are presented. The first approach uses oscillatory parameters measured under normoxic conditions, expressed as flowmotion (FM), vasomotion (VM), and the normoxia oscillatory index (NOI). These parameters have been used for the identification of impaired microcirculatory oscillations associated with intense physical exercise, post-COVID syndrome, psychological stress, and erectile dysfunction. The second approach involves characterization of the microcirculatory response to hypoxia based on the measurement of hypoxia sensitivity (HS). The HS parameter is used to characterize microvascular complications in diabetes, such as diabetic kidney disease and diabetic foot ulcers. Based on research conducted by the authors of this review, the FMSF parameter ranges characterizing microvascular function are presented. The diagnostic approach to assessing microvascular function based on flowmotion monitored by the FMSF technique has a wide range of applications and the potential to be integrated into widespread medical practice.

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.

Efficacy of Low-Molecular-Weight Heparin in the Treatment of Severe Acute Pancreatitis: A Comparative Study at a Tertiary Health Center.

Introduction Acute pancreatitis is caused by multiple factors. The disease can progress to severe acute pancreatitis (SAP) rapidly, which is a fatal condition. SAP is associated with systemic inflammatory response and disturbances in microcirculation, which are responsible for the high rate of mortality. Low-molecular-weight heparin (LMWH), apart from preventing thrombus formation, also has a property of reducing the release of cytokines and inflammatory mediators. This aids in the improvement of microcirculation of the pancreas. Materials and methods A prospective hospital-based study was conducted on 60 patients diagnosed with SAP. Patients were randomly divided into two groups: conventional treatment group (C group consisting of 30 patients) and LMWH in addition to conventional treatment (L group, consisting of 30 patients). Clinical and laboratory parameters and computed tomography (CT) scores of pancreatic necrosis (CTSPN) were compared in the two study groups. Results No significant difference (p > 0.05) was observed in the clinical and laboratory parameters and CTSPN among the two study groups at the time of admission. On initiation of treatment, the rate of improvement in symptoms and laboratory parameters were significantly higher in the L group compared with the C group (p < 0.05). Acute physiology and chronic health evaluation (APACHE) II score and development of complications were significantly lower in the L group compared with the C group (p< 0.05). CTSPN was found to be very low in the L group compared with the C group (p < 0.05). After two weeks of treatment, the recovery rate in response to treatment was observed to be higher in the L group compared to the C group, and the mortality rate was very low in the L group (p <0.05, significant). Conclusion The addition of LMWH to conventional treatment in SAP augments the effect and improves the clinical response, improving the recovery rate and decreasing mortality. LMWH is highly effective for the treatment of SAP, with a good safety profile and easy availability and without high financial burden.

Which CAP components are relevant for enhancing dermal microcirculation in intact skin?

Cold atmospheric plasma (CAP) has been shown to be beneficial in various medical fields such as wound healing, oncology or dentistry. A prominent effect induced by CAP is the boost of microcirculation in human skin tissue. Being a complex cocktail of physical and chemically reactive components, the mechanisms by which CAP enhances microcirculation still remain unclear. Thus, this study aims to identify relevant CAP components involved in stimulation of dermal microcirculation. In a comparative approach, the application of the same CAP source was modified in such a way that three different treatment modalities could be realized, each with a characteristic composition of electrical current flow and concentration of reactive species. Microcirculation parameters oxygen saturation (StO2), tissue hemoglobin index, near-infrared perfusion index and tissue water index were recorded before and after each treatment on the lateral proximal left arm of 10 healthy volunteers by means of hyperspectral imaging. The maximum microcirculatory response to CAP was observed when all components were allowed to interact with skin tissue (standard treatment). In contrast, no upregulation was found as soon as electric currents and fields had been removed from the effective component spectrum. Application of the CAP source at reduced concentrations of reactive species compared to standard treatment led to significant but less pronounced enhancement of dermal microcirculation. The findings of this study indicate that a synergistic interplay of all CAP components promotes microcirculation in dermal tissue most effectively. Moreover, the findings support the hypothesis that electric currents and fields play a key role in enabling microcirculation boost whereas availability of reactive species in the gas phase is associated with the intensity of the tissue response to CAP treatment.

Hypoxia impairs Kv7 channel function in the coronary microcirculation

Ischemic heart disease (IHD) is a multifaceted pathological manifestation that continues to press an extensive burden on individuals and healthcare resources. The strenuous weight of this disease affects more than 80 million people in the United States, with an annual economic cost of more than $300 billion in healthcare expenses and lost productivity. Understanding the progression of this disease and the underlying regulatory mechanisms is essential for dampening the substantial socio-economic burden it poses by supporting the development of novel therapeutic strategies for afflicted patients. Myocardial perfusion is largely controlled by the microcirculation, consisting of small arteries and arterioles. Under physiological conditions, an increase in myocardial metabolic activity stimulates coronary vasodilation and increased vascular perfusion. However, pathological coronary stenosis of the conduit arteries impairs downstream flow and O2 delivery that must be compensated by collateral supply from neighboring nonoccluded regions. The ability of the vasculature to dilate in response to a reduction in flow is paramount for improved perfusion from the collateral circulation. Voltage-gated potassium (Kv) channels present as significant end effectors of vasodilation for many signaling axes, including reactive oxygen species, which are reported to be upregulated under ischemic conditions. Using the clinically relevant swine model for the current study, we isolate a reduction in oxygen tension, ex vivo, as a single characteristic of an otherwise complicated disease and test the hypothesis that hypoxic insult impairs Kv7 channel function. Isometric tension wire myography and perforated patch voltage clamp were used to investigate Kv7 channel contribution to H2O2-mediated vasodilation and Kv channel currents in response to hypoxic insult. Our data reveal that hypoxic conditions impair H2O2-mediated vasodilation and that this impairment is attributable, at least in part, to a loss of Kv7 channel activation. Further, protein kinases are known to associate with and activate Kv7 channels in other tissue types. Inhibition of protein kinase A (PKA) yields a similar inhibitory response to blockade of Kv7 channels. Taken together, these studies reveal Kv7 channels as potential targets of hypoxic insult, and their reduced contribution may be responsible for impaired vasoreactivity in the coronary microcirculation in response to hypoxic insult. Funding: NIH RO1 HL139903. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor-specific pain phenotype.

Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor-sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex-mediated microcirculatory responses. Cold-pressor-sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor-mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber-mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water-exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Skin microcirculatory responses: A potential marker for early diabetic neuropathy assessment using a low-cost portable diffuse optical spectrometry device.

Diffuse optical measurement is an evolving optical modality providing a fast and portable solution for microcirculation assessment. Diffuse optics in static and dynamic modalities are combined here in a system to assess hemodynamics in skin tissues of control and diabetic subjects. The in-house developed system consists of a laser source, fiber optic probe, a low-cost avalanche photodiode, a finite element model (FEM) derived static optical property estimator, and a software correlator for continuous flow monitoring through microvasculature. The studies demonstrated that the system quantifies the changes in blood flow rate in the immediate skin subsurface. The system is calibrated with in vitro flow models and a proof-of-concept was demonstrated on a limited number of subjects in a clinical environment. The flow changes in response to vasoconstrictive and vasodilative stimuli were analyzed and used to classify different stages of diabetes, including diabetic neuropathy.

Evaluating transient phenomena by wavelet analysis: early recovery to exercise.

Wavelet analysis (WA) provides superior time-frequency decomposition of complex signals than conventional spectral analysis tools. To illustrate its usefulness in assessing transient phenomena, we applied a custom-developed WA algorithm to laser-Doppler (LD) signals of the cutaneous microcirculation measured at glabrous (finger pulp) and nonglabrous (forearm) sites during early recovery after dynamic exercise. This phase, importantly contributing to the establishment of thermal homeostasis after exercise cessation, has not been adequately explored because of its complex, transient form. Using WA, we decomposed the LD signals measured during the baseline and early recovery into power spectra of characteristic frequency intervals corresponding to endothelial nitric oxide (NO)-dependent, neurogenic, myogenic, respiratory, and cardiac physiological influence. Assessment of relative power (RP), defined as the ratio between the median power in the frequency interval and the median power of the total spectrum, revealed that endothelial NO-dependent (5.87 early recovery; 1.53 baseline; P = 0.005; Wilcoxon signed-rank test) and respiratory (0.71 early recovery; 0.40 baseline; P = 0.001) components were significantly increased, and myogenic component (1.35 early recovery; 1.83 baseline; P = 0.02) significantly decreased during early recovery in the finger pulp. In the forearm, only the RP of the endothelial NO-dependent (1.90 early recovery; 0.94 baseline; P = 0.009) component was significantly increased. WA presents an irreplaceable tool for the assessment of transient phenomena. The relative contribution of the physiological mechanisms controlling the microcirculatory response in the early recovery phase appears to differ in glabrous and nonglabrous skin when compared with baseline; moreover, the endothelial NO-dependent influence seems to play an important role.NEW & NOTEWORTHY We address the applicability of wavelet analysis (WA) in evaluating transient phenomena on a model of early recovery to exercise, which is the only exercise-associated phase characterized by a distinct transient shape and as such cannot be assessed using conventional tools. Our WA-based algorithm provided a reliable spectral decomposition of laser-Doppler (LD) signals in early recovery, enabling us to speculate roughly on the mechanisms involved in the regulation of skin microcirculation in this phase.

Morphological features of the photoplethysmographic signal: a new approach to characterize the microcirculatory response to photobiomodulation.

Introduction and Objectives: Advanced analysis of the morphological features of the photoplethysmographic (PPG) waveform may provide greater understanding of mechanisms of action of photobiomodulation (PBM). Photobiomodulation is a non-ionizing, red to near-infrared irradiation shown to induce peripheral vasodilatation, promote wound healing, and reduce pain. Using laser Doppler flowmetry combined with thermal imaging we found previously in a clinical study that PBM stimulates microcirculatory blood flow and that baseline palm skin temperature determines, at least in part, why some individuals respond favorably to PBM while others do not. "Responders" (n = 12) had a skin temperature range of 33°C-37.5°C, while "non-responders" (n = 8) had "cold" or "hot" skin temperature (<33°C or >37.5°C respectively). The continuous PPG signals recorded from the index fingers of both hands in the original clinical study were subjected to advanced post-acquisitional analysis in the current study, aiming to identify morphological features that may improve the accuracy of discrimination between potential responders and non-responders to PBM. Methods: The PPG signals were detrended by subtracting the lower envelope from the raw signal. The Root Mean Square (RMS) and Entropy features were extracted as were two additional morphological features -- Smoothness and number of local extrema per PPG beat (#Extrema). These describe the signal jaggedness and were developed specifically for this study. The Wilcoxon test was used for paired comparisons. Correlations were determined by the Spearman correlation test (rs). Results: The PPG waveforms of responders to PBM had increased amplitude and decreased jaggedness (Baseline vs. 10' post-irradiation: Entropy, 5.0 ± 1.3 vs. 3.9 ± 1.1, p = 0.012; #Extrema, 4.0 ± 1.1 vs. 3.0 ± 1.6, p = 0.009; RMS, 1.6 ± 0.9 vs. 2.3 ± 1.2, p = 0.004; Smoothness, 0.10 ± 0.05 vs. 0.19 ± 0.16, p = 0.016). In addition, unilateral irradiation resulted in a bilateral response, although the response of the contralateral, non-irradiated hand was shorter in duration and lower in magnitude. Although subjects with 'cold,' or 'hot,' baseline skin temperature appeared to have morphologically distinct PPG waveforms, representing vasoconstriction and vasodilatation, these were not affected by PBM irradiation. Conclusion: This pilot study indicates that post-acquisitional analysis of morphological features of the PPG waveform provides new measures for the exploration of microcirculation responsiveness to PBM.

Assessment of the Microcirculation in Superficial and Deep Biotissue with Photobiomodulation

Background Quantitative measurement of blood flow in specific biotissue targets is crucial for photobiomodulation therapy (PBMT). PBMT has been applied on many clinical applications. However, the conclusive confirmation of its effects on microcirculation and laser wavelength dependency in superficial and deep tissues is lacking. Objective This study examines the microcirculatory response and laser wavelength dependency of red and near infrared (NIR) lasers in biotissue. Laser Doppler flowmetry (LDF) was used to assess the flux and velocity of erythrocytes in buccal tissue when exposed to 660 nm and 830 nm laser radiation. Discussion The microcirculatory response of subjects during and after laser radiation were analyzed. Each laser has an energy density of 73.17 J/cm2 . Both the 660 nm and 830 nm lasers demonstrated the capability to enhance microcirculation in both superficial and deep tissues. Furthermore, we observed that laser wavelengths at 660 nm and 830 nm respectively enhanced the microcirculatory response in superficial and deep tissues. Importantly, this cumulative effect persisted for at least 10 minutes. Conclusions The present results indicate that PBM can effectively improve local blood perfusion in specific target areas and peripheral biotissues. These findings have potential applications in enhancing wound healing and local microcirculation within the target areas.

Interleukin-36 is vasculoprotective in both sexes despite sex-specific changes in the coronary microcirculation response to IR injury.

Risks and outcomes of myocardial infarction (MI) are different between men and women and some studies have demonstrated that the latter have a higher risk of mortality. Whilst there are many reasons for this, it may also partially be linked to stronger innate and adaptive immune responses mounted by females compared to males. However, little is known about how sex impacts the coronary microvessels, the site where inflammatory processes take place, after an MI. Intravital and laser speckle microscopy was used to image coronary microvessels and ventricular perfusion in vivo in response to myocardial ischaemia-reperfusion (IR) injury in male and female mice. Interleukin-36 (IL-36) is the latest addition to the IL-1 superfamily of pro-inflammatory cytokines and has recently been shown to mediate inflammation in a number of non-cardiovascular diseases. Its role in mediating potential sex-related microcirculatiory pertubations in the heart are unknown. Therefore, the vasculoprotective efficacy of an IL-36 receptor antagonist (IL-36Ra) was also investigated. Immunostaining and flow cytometry demonstrated higher expression of IL-36 and its receptor in female hearts, an observation confirmed in human samples. Intravital imaging of the anaesthetised mouse beating heart identified significantly greater neutrophil recruitment in female hearts, but a greater burden of thrombotic disease in male hearts. Male mice had reduced functional capillary density and were unable to restore perfusion to baseline values as effectively as females. However, female mice had significantly larger infarcts. Interestingly, IL-36Ra decreased inflammation, improved perfusion, and reduced infarct size in both sexes despite increasing platelet presence in male hearts. Mechanistically, this was explained by IL-36Ra attenuating endothelial oxidative damage and VCAM-1 expression. Importantly, IL-36Ra administration during ischaemia was critical for vasculoprotection to be realised. This novel study identified notable sex-related differences in the coronary microcirculatory response to myocardial IR injury which may explain why some studies have noted poorer outcomes in women after MI. Whilst contemporary MI treatment focuses on anti-platelet strategies, the heightened presence of neutrophils in female IR injured coronary microvessels necessitates the development of an effective anti-inflammatory approach for treating female patients. We also emphasise the importance of early intervention during the ischaemic period in order to maximise therapeutic effectiveness.

Sex Variations in Retinal Microcirculation Response to Lower Body Negative Pressure.

Lower body negative pressure (LBNP) is routinely used to induce central hypovolemia. LBNP leads to a shift in blood to the lower extremities. While the effects of LBNP on physiological responses and large arteries have been widely reported, there is almost no literature regarding how these cephalad fluid shifts affect the microvasculature. The present study evaluated the changes in retinal microcirculation parameters induced by LBNP in both males and females. Forty-four participants were recruited for the present study. The retinal measurements were performed at six time points during the LBNP protocol. To prevent the development of cardiovascular collapse (syncope) in the healthy participants, graded LBNP until a maximum of -40 mmHg was applied. A non-mydriatic, hand-held Optomed Aurora retinal camera was used to capture the retinal images. MONA Reva software (version 2.1.1) was used to analyze the central retinal arterial and venous diameter changes during the LBNP application. Repeated measures ANOVAs, including sex as the between-subjects factor and the grade of the LBNP as the within-subjects factor, were performed. No significant changes in retinal microcirculation were observed between the evaluated time points or across the sexes. Graded LBNP application did not lead to changes in the retinal microvasculature across the sexes. The present study is the first in the given area that attempted to capture the changes in retinal microcirculation caused by central hypovolemia during LBNP. However, further research is needed with higher LBNP levels, including those that can induce pre-fainting (presyncope), to fully understand how retinal microcirculation adapts during complete cardiovascular collapse (e.g., during hypovolemic shock) and/or during severe hemorrhage.

Effect of norepinephrine on the vascular waterfall and tissue perfusion in vasoplegic hypotensive patients: a prospective, observational, applied physiology study in cardiac surgery

BackgroundNorepinephrine is a commonly used drug for treating vasoplegic acute circulatory failure in ICU. The prediction of norepinephrine macro- and micro-circulatory response is complicated by its uneven receptors’ distribution between the arterial and the venous structures, and by the presence of a physiological vascular waterfall (VW) that disconnects the arterial and the venous circulation in two pressure systems. The objectives of this study were to describe the VW in patients with arterial hypotension due to vasodilatory circulatory shock, and its behavior according to its response to norepinephrine infusion.MethodsA prospective, observational, bi-centric study has included adult patients, for whom the physician decided to initiate norepinephrine during the six first hours following admission to the ICU after cardiac surgery, and unresponsive to a fluid challenge. The mean systemic pressure (MSP) and the critical closing pressure (CCP) were measured at inclusion and after norepinephrine infusion.ResultsThirty patients were included. Norepinephrine increased arterial pressure and total peripheral resistances in all cohort. The cohort was dichotomized as VW responders (patients with a change of VW over the least significant change (≥ 93% increase in VW)), and as VW non-responders. In 19 (63%) of the 30 patients, VW increased from 3.47 [− 14.43;7.71] mmHg to 43.6 [25.8;48.1] mmHg, p < 0.001) with norepinephrine infusion, being classified as VW responders. The VW responders improved cardiac index (from 1.8 (0.6) L min−1 m−2 to 2.2 (0.5) L min−1 m−2, p = 0.002), capillary refill time (from to 4.2 (1.1) s to 3.1 (1) s, p = 0.006), and pCO2 gap (from 9 [7;10] mmHg to 6 [4;8] mmHg, p = 0.04). No baseline parameters were able to predict the VW response to norepinephrine. In comparison, VW non-responders did not significantly change the VW (from 5 [-5;16] mmHg to -2 [-12;15] mmHg, p = 0.17), cardiac index (from 1.6 (0.3) L min−1 m−2 to 1.8 (0.4) L min−1 m−2, p = 0.09) and capillary refill time (from 4.1 (1) s to 3.7 (1.4), p = 0.44).ConclusionsIn post-cardiac surgery patients with vasoplegic arterial hypotension, the vascular waterfall is low. Norepinephrine did not systematically restore the vascular waterfall. Increase of the vascular waterfall was associated with an improvement of laboratory and clinical parameters of tissue perfusion.

Videocapillaroscopic monitoring of microcirculation in rats during photodynamic therapy

The proposed approach to microcirculation assessment is non-invasive, informative, and can be implemented during photoactivation, and thus is perspective both for research tasks and clinical practice. The functional principles of the vasculature response to photodynamic exposure, identified using this technique, also foster the efficiency and safety of photodynamic therapy. The developed setup allows simultaneous photodynamic exposure and studying the microcirculation parameters by videocapillaroscopy and photoplethysmography techniques. Photodynamic action is carried out by 662 nm laser radiation with a power density of 15 mW/cm2 in continuous and pulsed modes. The imaging system of the setup consists of a large working distance microscope, an optical filter, and a monochrome camera. The illumination system is based on LED with a central wavelength of 532 nm. The acquired images were processed in order to obtain morphometric and hemodynamic microcirculation data in the inspected skin area. To compare the proposed approach with existing methods, we measured blood flow parameters by a laser Doppler flowmeter. We tested the developed setup on rats injected with a photosensitizer and obtained active vessel maps, photoplethysmograms, and skin vessel density values before, during, and after photoactivation in both generation modes. The proposed approach allows to reveal differences in the microcirculation response to photodynamic effects of low power densities in different modes, in particular, the discrepancy between the time from the start of exposure to the cessation of blood flow and the start of the recovery period.

Serum uric acid: a futile bystander in endothelial function?

Purpose This study aims to investigate the relationship between serum uric acid levels and endothelial function, oxidative stress, and hemodynamic parameters, and to determine if uric acid levels provide additional insights beyond traditional factors like ageing and hypertension in volunteers with low cardiovascular risk factors. Serum uric acid is known for its antioxidant properties, but it may also contribute to cardiovascular risk. Materials and Methods The study enrolled 40 male participants, divided into three groups based on age and blood pressure status. Group 1 comprised younger participants, group 2 included older individuals without hypertension, and group 3 consisted of older patients with hypertension. The study assessed endothelial function using laser Doppler imaging and measured acetylcholine- and sodium nitroprusside-induced hyperaemia. The heat microcirculatory response was also examined in the presence of L-NAME, an inhibitor of NOS synthase. The study evaluated oxidative stress and arterial stiffness by measuring allantoin, angiotensin II, Homocitrulline/Lysine, and Chloro-Tyrosine/Tyrosine ratios, as well as by performing non-invasive measurements of aortic augmentation indexes and carotid-femoral pulse wave velocity. Results The study found that uric acid levels did not differ significantly among the three groups. Augmentation indexes increased with ageing, but hypertension did not have an additional effect. Blood pressure and carotid-femoral pulse wave velocity differed among the groups, with the lowest values among younger participants and the highest values among older individuals with hypertension. Allantoin and angiotensin II levels did not differ among the groups. However, Homocitrulline/Lysine and Chloro-Tyrosine/Tyrosine ratios were significantly lower in young subjects. Correlation and multivariable analysis showed that uric acid had no effect on any of the studied parameters. Despite a strong association between ageing and systolic blood pressure with impaired endothelial function, oxidative stress, and arterial stiffness, only ageing retained a significant effect in the multivariable analysis. Conclusion In healthy or hypertensive adults with normal renal function, serum uric acid appears to be a futile bystander in endothelial function, oxidative stress, and arterial stiffness, in contrast to ageing, which reduces NO bioavailability. This study suggests that traditional factors such as ageing and hypertension should be the focus of clinical assessment and management of cardiovascular risk, rather than uric acid levels.

Non-invasive intradialytic percutaneous perfusion monitoring: a view to the heart through the skin.

The life-sustaining treatment of hemodialysis (HD) induces recurrent and cumulative systemic circulatory stress resulting in cardiovascular injury. These recurrent insults compound preexisting cardiovascular sequalae leading to the development of myocardial injury and resulting in extremely high morbidity/mortality. This is largely a consequence of challenged microcirculatory flow within the myocardium (evidenced by detailed imaging-based studies). Currently, monitoring during HD is performed at the macrovascular level. Non-invasive monitoring of organ perfusion would allow the detection and therapeutic amelioration of this pathophysiological response to HD. Non-invasive percutaneous perfusion monitoring of the skin (using photoplethysmography-PPG) has been shown to be predictive of HD-induced myocardial stunning (a consequence of segmental ischemia). In this study, we extended these observations to include a dynamic assessment of skin perfusion during HD compared with directly measured myocardial perfusion during dialysis and cardiac contractile function. We evaluated the intradialytic microcirculatory response in 12 patients receiving conventional HD treatments using continuous percutaneous perfusion monitoring throughout HD. Cardiac echocardiography was performed prior to the initiation of HD, and again at peak-HD stress, to assess the development of regional wall motion abnormalities (RWMAs). Myocardial perfusion imaging was obtained at the same timepoints (pre-HD and peak-HD stress), utilizing intravenous administered contrast and a computerized tomography (CT)-based method. Intradialytic changes in pulse strength (derived from PPG) were compared with the development of HD-induced RWMAs (indicative of myocardial stunning) and changes in myocardial perfusion. We found an association between the lowest pulse strength reduction (PPG) and the development of RWMAs (p = 0.03) and also with changes in global myocardial perfusion (CT) (p = 0.05). Ultrafiltration rate (mL/kg/hour) was a significant driver of HD-induced circulatory stress [(associated with the greatest pulse strength reduction (p = 0.01), a reduction in global myocardial perfusion (p = 0.001), and the development of RWMAs (p = 0.03)]. Percutaneous perfusion monitoring using PPG is a useful method of assessing intradialytic hemodynamic stability and HD-induced circulatory stress. The information generated at the microcirculatory level of the skin is reflective of direct measures of myocardial perfusion and the development of HD-induced myocardial stunning. This approach for the detection and management of HD-induced cardiac injury warrants additional evaluation.

Pulmonary Microcirculation in Experimental Model of Pulmonary Thromboembolism after Pretreatment with Chloroquine.

Changes of pulmonary microcirculation in response to pulmonary artery embolization after pretreatment with chloroquine were studied on the model of isolated perfused rabbit lungs. The increase in the pulmonary vascular resistance and pre- and postcapillary resistance was less pronounced than after pulmonary thromboembolism after pretreatment with mibefradil (T-type Ca2+ channels blocker) or nifedipine (L-type Ca2+ channels blocker). The shifts of capillary filtration coefficient correlated with changes in the precapillary resistance. When modeling pulmonary thromboembolism after pretreatment with chloroquine combined with glibenclamide (KATP channels blocker), the studied hemodynamics parameters increased to the same extent as after pretreatment with nifedipine. The results indicate that chloroquine exhibits the properties of an L- and T-type Ca2+ channels blocker and an activator of KATP channels.

Microcirculatory response to cold stress test in the healthy hand.

Cold sensitivity of the fingers is common in several conditions. It has been linked to digital vasospasm, microvascular dysfunction, and neural mechanisms. This study aimed to investigate the normal digital microvascular response to a cold stress test in healthy individuals using Laser Speckle Contrast Imaging (LSCI). Twenty-six healthy individuals, mean age 31 (SD 9) years were included. Skin perfusion of digits II-V was measured using Laser Speckle Contrast Imaging before and after a standardized cold stress test. Changes in skin perfusion from baseline were analyzed between hands, digits, and sexes. Skin perfusion was significantly (p<0.0001) affected by cold provocation in both the cold exposed and the contralateral hands in all participants of the study. This effect was significantly different between the radial (digit II and III) and the ulnar (digit V) side of the hands (p<0.001). There was a trend towards a larger decrease in perfusion in men (ns), and a faster recovery to baseline values in women (ns). A larger inter subject variability was seen in perfusion values in women. The normal microvascular response to cold provocation may involve both centrally and regionally mediated processes. When exposing one hand to a cold stress test, the contralateral hand responds with simultaneous but smaller decreases in perfusion.

Functional Evaluation of Microcirculation in Response to Fluid Resuscitation in Hypovolemic Adult Post-cardiac Surgical Patients

Objectives: Microcirculation is bound to be altered during cardiac surgery due to multiple factors, mainly the intense systemic inflammatory response syndrome which peaks in the first 24-h postoperatively. Decreased microvascular flow associated with increased postoperative morbidity has been reported. The literature suggests a potential independence of macrocirculation and microcirculation during fluid loading. The present study was conducted to assess thenar muscle tissue oxygen saturation (StO2) changes during vascular occlusion test (VOT) in response to hypovolemia and to assess the dynamic responses of the StO2 variables post-volume expansion (VE). Material and Methods: Thirty-five adult post-cardiac surgical patients, with stroke volume (SV) variation &gt;12% were included in the study. Fifty-two fluid challenges were studied. Functional evaluation of microcirculation using VOT and near infrared spectroscopy (NIRS) variables along with monitoring of macrocirculatory indices was performed before and after VE. Statistical analysis was done using Student t-test. Results: Post-VE, 34 were responders with increase in SV ≥15% and 18 were non-responders (SV &lt;15%). Rate of resaturation was significantly faster in responders compared to non-responders after VE (P = 0.0293 vs. P = 0.1480). However, macrocirculatory indices including cardiac output, SV, and delivery of oxygen showed significant improvement in both responders and non-responders. Conclusion: Preload dependence is associated with significant change in the StO2 recovery slope measured at the thenar eminence in volume responders. Functional evaluation of microcirculation using VOT and StO2 can be a useful complimentary tool along with the macrocirculatory indices for optimal fluid rescuscitaion in adult post-cardiac surgical patients.