Vasoconstriction Research Articles

Efficiency of an algorithm for the prevention of sternal infection after cardiac surgery in children under 1 year of age: A single-center retrospective study

BackgroundSternal infection is one of the most challenging complications to manage after heart surgery. The aim of our study is to evaluate the effectiveness of a developed algorithm for preventing sternal infection in pediatric patients after surgery for congenital heart disease (CHD). MethodsWe conducted a single-center study examining the treatment of 478 children with CHD. Patients were divided into 2 groups, taking into account the application of a developed management algorithm. A multivariate logistic regression analysis was used to identify the factors influencing the development of sternal infection following heart surgery using median sternotomy. ResultsA developed algorithm was applied in 308 children. In total, there were 16 cases of sternal infection (3.34 %) across both groups. Deep wound infection developed in 6 patients (1.26 %). Sternal infection developed in 2 children (0.65 %) in the first group (in which the algorithm was applied) and 14 children (8.2 %) in the second group. Deep sternal infection developed in 1 patient in the first group (0.33 %) and in 5 patients in the second group (2.94 %). As a result, perioperative risk factors as postoperative resternotomy (OR 23.315; p < 0.001), delayed sternal closure (OR 9.087; p = 0.003), development of acute renal failure (OR 5.322; p = 0.018) were associated with increased risk of infection and application of the developed algorithm resulted in a significant reduction in risk (OR 0.032; p < 0.001). ConclusionThe suggested method for the prevention of sternal infection has significantly reduced the incidence of sternal infection after cardiac surgery in children less than 1 year of age. In patients with moderate to high risk for surgical site infection, surgeons can enhance wound healing and prevent wound infections with simple, inexpensive, and readily available tools and techniques. Surgical aspects, topical use of antibiotics, prevention of peripheral vasoconstriction, maintenance of normal oxygen delivery rates, and an individual approach to intensive care are essential.

Comparing multimodal physiological responses to social and physical pain in healthy participants.

Previous physiology-driven pain studies focused on examining the presence or intensity of physical pain. However, people experience various types of pain, including social pain, which induces negative mood; emotional distress; and neural activities associated with physical pain. In particular, comparison of autonomic nervous system (ANS) responses between social and physical pain in healthy adults has not been well demonstrated. We explored the ANS responses induced by two types of pain-social pain, associated with a loss of social ties; and physical pain, caused by a pressure cuff-based on multimodal physiological signals. Seventy-three healthy individuals (46 women; mean age = 20.67 ± 3.27 years) participated. Behavioral responses were assessed to determine their sensitivity to pain stimuli. Electrocardiogram, electrodermal activity, photoplethysmogram, respiration, and finger temperature (FT) were measured, and 12 features were extracted from these signals. Social pain induced increased heart rate (HR) and skin conductance (SC) and decreased blood volume pulse (BVP), pulse transit time (PTT), respiration rate (RR), and FT, suggesting a heterogeneous pattern of sympathetic-parasympathetic coactivation. Moreover, physical pain induced increased heart rate variability (HRV) and SC, decreased BVP and PTT, and resulted in no change in FT, indicating sympathetic-adrenal-medullary activation and peripheral vasoconstriction. These results suggest that changes in HR, HRV indices, RR, and FT can serve as markers for differentiating physiological responses to social and physical pain stimuli.

Blood oxygen transport and depletion in diving emperor penguins.

Oxygen store management underlies dive performance and is dependent on the slow heart rate and peripheral vasoconstriction of the dive response to control tissue blood flow and oxygen uptake. Prior research has revealed two major patterns of muscle myoglobin saturation profiles during dives of emperor penguins. In Type A profiles, myoglobin desaturated rapidly, consistent with minimal muscle blood flow and low tissue oxygen uptake. Type B profiles, with fluctuating and slower declines in myoglobin saturation, were consistent with variable tissue blood flow patterns and tissue oxygen uptake during dives. We examined arterial and venous blood oxygen profiles to evaluate blood oxygen extraction and found two primary patterns of venous hemoglobin desaturation that complemented corresponding myoglobin saturation profiles. Type A venous profiles had a hemoglobin saturation that (a) increased/plateaued for most of a dive's duration, (b) only declined during the latter stages of ascent, and (c) often became arterialized [arterio-venous (a-v) shunting]. In Type B venous profiles, variable but progressive hemoglobin desaturation profiles were interrupted by inflections in the profile that were consistent with fluctuating tissue blood flow and oxygen uptake. End-of-dive saturation of arterial and Type A venous hemoglobin saturation profiles were not significantly different, but did differ from those of Type B venous profiles. These findings provide further support that the dive response of emperor penguins is a spectrum of cardiac and vascular components (including a-v shunting) that are dependent on the nature and demands of a given dive and even of a given segment of a dive.

Oxy-Inflammation in Humans during Underwater Activities.

Underwater activities are characterized by an imbalance between reactive oxygen/nitrogen species (RONS) and antioxidant mechanisms, which can be associated with an inflammatory response, depending on O2 availability. This review explores the oxidative stress mechanisms and related inflammation status (Oxy-Inflammation) in underwater activities such as breath-hold (BH) diving, Self-Contained Underwater Breathing Apparatus (SCUBA) and Closed-Circuit Rebreather (CCR) diving, and saturation diving. Divers are exposed to hypoxic and hyperoxic conditions, amplified by environmental conditions, hyperbaric pressure, cold water, different types of breathing gases, and air/non-air mixtures. The "diving response", including physiological adaptation, cardiovascular stress, increased arterial blood pressure, peripheral vasoconstriction, altered blood gas values, and risk of bubble formation during decompression, are reported.

Ultrasound images of the ascending aorta of anesthetized northern fur seals and Steller sea lions confirm that the aortic bulb maintains continuous blood flow.

The increased size and enhanced compliance of the aortic bulb-the enlargement of the ascending aorta-are believed to maintain blood flow in pinnipeds during extended periods of diastole induced by diving bradycardia. The aortic bulb has been described ex vivo in several species of pinnipeds, but in vivo measurements are needed to investigate the relationship between structure and function. We obtained ultrasound images using electrocardiogram-gated transesophageal echocardiography during anesthesia and after atropine administration to assess the relationship between aortic bulb anatomy and cardiac function (heart rate, stroke volume, cardiac output) in northern fur seals (Callorhinus ursinus) and Steller sea lions (Eumetopias jubatus). We observed that the aortic bulb in northern fur seals and Steller sea lions expands during systole and recoils over the entire diastolic period indicating that blood flow is maintained throughout the entire cardiac cycle as expected. The stroke volumes we measured in the fur seals and sea lions fit the values predicted based on body size in mammals and did not change with increased heart rates, suggesting that greater stroke volumes are not needed for aortic bulb function. Overall, our results suggest that peripheral vasoconstriction during diving is sufficient to modulate the volume of blood in the aortic bulb to ensure that flow lasts over the entire diastolic period. These results indicate that the shift of blood into the aortic bulb of pinnipeds is a fundamental mechanism caused by vasoconstriction while diving, highlighting the importance of this unique anatomical adaptation.

Hypovolemic shock Hypovolemic Shock: How Does Lactic Acid Affect the Heart?

Hypovolemic shock is due to a critical loss in the effective circulating blood volume with systemic hypoperfusion. If left untreated, hypovolemic shock can lead to ischemic injury of vital organs, leading to multi-system organ failure and death. Hypovolemic shock is a potentially life-threatening condition (1,2). There are five causes of hypovolemic shock: hemorrhage, trauma, surgical intervention, burns, and fluid loss caused by vomiting or diarrhea. This woman was involved in a motor vehicle accident, which resulted in a traumatic crash (2,3). This was caused by blood loss to the abdomen, as the physical examination suggested (3). Early recognition and appropriate management are essential. Hypovolemic shock results from depletion of intravascular volume, whether by extracellular fluid loss or blood loss (1,2). The pre-shock stage is characterized by compensatory mechanisms with increased sympathetic tone resulting in increased heart rate, increased cardiac contractility, and peripheral vasoconstriction (2,3).

Guyton perspective in managing peripartum cardiomyopathy patient with pulmonary edema: a case report

BackgroundPeripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related condition characterized by left ventricular dysfunction and heart failure, typically occurring in the peripartum period. Individuals with a history of preeclampsia and hypertension are particularly prone to developing PPCM. Recent research suggests that the condition may be triggered by vascular dysfunction influenced by maternal hormones in the late stages of gestation. The onset of left heart failure results in decreased cardiac output, leading to insufficient perfusion, which in turn, contributes to pulmonary edema and exacerbates tissue hypoxia. This cardiovascular response activates the neurohumoral system, causing peripheral vasoconstriction and elevating both mean capillary filling pressure (MCFP) and central venous pressure (CVP). Early administration of furosemide reduces volume overload due to negative cumulative fluid balance gaining and vasodilation, which increases the velocity of intravascular refilling and causes interstitial edema to resolve. This will decrease interstitial fluid pressure, resulting in decreased mechanical compression to systemic capillary and systemic vein pressure, thus decreasing MCFP and CVP subsequently. Reduced CVP also contributes to increased venous return by decreasing the gradient pressure between MCFP and CVP, resulting in increased cardiac output (CO) and improved tissue oxygenation.CaseA 33-year-old Asian woman, para 3 at full term pregnancy, admitted to the intensive care unit (ICU) after c-section and tubectomy due to shortness of breath and palpitation. Based on history taking, physical examination and echocardiography the patient fulfilled the criteria of PPCM which was also complicated by pulmonary edema. Despite impending respiratory failure, the patient rejected intubation and continuous positive airway pressure (CPAP), and was given oxygen supplementation through nasal cannula. Furosemide was given rapidly continued by maintenance dose and CVP was monitored. Antihypertensive drug, anticoagulants, and bromocriptine were also administered. After achieving negative cumulative fluid balance the patient’s symptoms resolved and was discharged one week later.ConclusionThere is a correlation between negative cumulative fluid balance and reduced central venous pressure after early furosemide therapy. Suspicion for PPCM should not be lowered in the presence of preeclampsia, it could delay appropriate treatment and increase the mortality.

THE RELATIONSHIP BETWEEN AGE AND DURATION OF SURGERY WITH THE INCIDENCE OF POST ANESTHESIA SHIVERING IN SECTION CAESAREAN PATIENTS AT BENDAN HOSPITAL PEKALONGAN CITY

Background: Shivering is a physiological response to exposure to cold and the body's next steps to maintain heat after peripheral vasoconstriction. The incidence of shivering is caused by several factors including age and length of surgery. Postanesthesia shivering is involuntary oscillatory muscle activity during early recovery after anesthesia. Objective: This study aims to determine the relationship between age and duration of surgery with the incidence of shivering after anesthesia in caesarean section patients at Bendan Hospital, Pekalongan City. Methods: This research includes quantitative research with the type of analytical correlational observational research with a cross sectional approach. The subjects or samples used were 50 caesarean section patients. Determination of subjects was carried out using consecutive sampling technique. Data collection was carried out using an observation sheet for the degree of shivering. Result: Based on the research, the results of the Spearman rank test were obtained with a value of (p) 0.0004 &lt; 0.05 between age and the incidence of shivering and p 0.000 &lt; 0.05 between the length of operation and the incidence of shivering. Conclusion: The conclusion of this study is that there is a relationship between age and length of operation and the incidence of post-anesthesia shivering in caesarean section patients.

Heat Stress but Not Capsaicin Application Alleviates the Hypertensive Response to Isometric Exercise

Heat stress and cutaneous capsaicin application act independently to reduce mean arterial blood pressure (MAP) at rest. The present study investigated whether a mixed intervention might alleviate to a greater extent the hypertensive response to isometric exercise. An end-exercise systolic blood pressure (SBP) lower than 215 mmHg or higher than 220 mmHg was set for the inclusion in the group observed with typical (CON, n = 9) or hypertensive (HRE, n = 8) response to dynamic exercise, respectively. The participants performed four trials held in thermoneutral (TN:23 °C) or hot (HT:33 °C) conditions with capsaicin (CA:4.8 mg·patch−1) or placebo (PL) patches (12 × 18 cm2) applied to their two quadriceps, left pectoralis major and left scapula. The trials comprised: a 5 min baseline period preceding patch application, a 30 min rest period and a 5 min isometric handgrip exercise (20% maximal voluntary contraction, 10.1 ± 1.9 kg). Thermoregulatory and cardiovascular data were analyzed using mixed three-way ANOVA. End-resting MAP and pain sensation were higher in PL-TN (p = 0.008) and CA-HT (p = 0.012), respectively. End-exercise SBP tended to be higher in HRE individuals across environments (p = 0.10). Total peripheral resistance and MAP remained lower in HT across groups (p &lt; 0.05). Despite the alleviating effect of the heat stressor, an augmented burning sensation-induced peripheral vasoconstriction might have blunted the pressure-lowering action of capsaicin.

Study of ischemic progression in different intestinal tissue layers during acute intestinal ischemia using swept-source optical coherence tomography angiography.

In acute intestinal ischemia, the progression of ischemia varies across different layers of intestinal tissue. We established a mouse model and used swept-source optical coherence tomography (OCT) to observe the intestinal ischemic process longitudinally in different tissue layers. Employing a method that combines asymmetric gradient filtering with adaptive weighting, we eliminated the vessel trailing phenomenon in OCT angiograms, reducing the confounding effects of superficial vessels on the imaging of deeper vasculature. We quantitatively assessed changes in vascular perfusion density (VPD), vessel length, and vessel average diameter across various intestinal layers. Our results showed a significant reduction in VPD in all layers during ischemia. The mucosa layer experienced the most significant impact, primarily due to disrupted capillary blood flow, followed by the submucosa layer, where vascular constriction or decreased velocity was the primary factor.

Impaired cardiopulmonary baroreflex function and altered cardiovascular responses to hypovolemia in patients with heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is associated with autonomic dysregulation, which may be related to baroreflex dysfunction. Thus, we tested the hypothesis that cardiac and peripheral vascular responses to baroreflex activation via lower-body negative pressure (LBNP; -10, -20, -30, -40 mmHg) would be diminished in patients with HFpEF (n = 10, 71 ± 7 yr) compared with healthy controls (CON, n = 9, 69 ± 5 yr). Changes in heart rate (HR), mean arterial pressure (MAP, Finapres), forearm blood flow (FBF, ultrasound Doppler), and thoracic impedance (Z) were determined. Mild levels of LBNP (-10 and -20 mmHg) were used to specifically assess the cardiopulmonary baroreflex, whereas responses across the greater levels of LBNP represented an integrated baroreflex response. LBNP significantly increased in HR in CON subjects at -30 and -40 mmHg (+3 ± 3 and +6 ± 5 beats/min, P < 0.01), but was unchanged in patients with HFpEF across all LBNP levels. LBNP provoked progressive peripheral vasoconstriction, as quantified by changes in forearm vascular conductance (FVC), in both groups. However, a marked (40%-60%) attenuation in FVC responses was observed in patients with HFpEF (-6 ± 8, -15 ± 6, -16 ± 5, and -19 ± 7 mL/min/mmHg at -10, -20, -30, and -40 mmHg, respectively) compared with controls (-15 ± 10, -22 ± 6, -25 ± 10, and -28 ± 10 mL/min/mmHg, P < 0.01). MAP was unchanged in both groups. Together, these data provide new evidence for impairments in cardiopulmonary baroreflex function and diminished cardiovascular responsiveness during hypovolemia in patients with HFpEF, which may be an important aspect of the disease-related changes in autonomic cardiovascular control in this patient group.NEW & NOTEWORTHY Data from the current study demonstrate diminished cardiovascular responsiveness during hypovolemia induced by incremental lower-body negative pressure in patients with heart failure with preserved ejection fraction (HFpEF). These diminished responses imply impaired cardiopulmonary baroreflex function and altered autonomic cardiovascular regulation which may represent an important aspect of HFpEF pathophysiology.

Optical Coherence Tomography Angiography: Investigating Vessel Density Changes Induced by Caffeine in Healthy Subjects.

Introduction: Caffeine, the most widely consumed psychoactive drug globally, has been associated with vascular changes in various organs, including the retina. Researchers have reported vascular constriction in the retina in response to caffeine, although data on its effects remain limited and somewhat contradictory. Further research is needed to clarify the specific impact of caffeine on retinal blood vessels and its potential implications for ocular health. Purpose: To investigate the effects of 200 mg of caffeine on systolic and diastolic blood pressure (SBP and DBP) and retinal vessel density (VD) assessed by optical coherence tomography angiography (OCTA). Methods: Prospective randomized, double-blind placebo-controlled, IRB-approved study in 59 healthy low caffeine users (< 136 mg of caffeine daily). Baseline 3 × 3 and 6 × 6 mm OCTA scans centered on the fovea as well as a 6 × 6 mm scans centered on the optic nerve head (ONH) were obtained. Participants were randomly assigned into caffeine group (CG, n = 42) receiving 200 mg caffeine pill or placebo group (PG, n = 17). OCTA scans were repeated at 60 and 120 min after intervention. VD was measured with Advanced Retina Imaging (ARI) network software (Carl Zeiss Meditec, Dublin, CA) for superficial capillary plexus (SCP) and deep capillary plexus (DCP). SBP/DBP readings were recorded before each imaging session. Ordinary one-way analysis of variance (ANOVA) of each group was performed using GraphPad Prism Version 9.3.0. Results: Both groups had comparable demographics and OCTA parameters at baseline. Two hours after intervention, the CG had a significantly higher SBP (123 ± 7 mmHg) and DBP (81 ± 5 mmHg) compared to the control group (118 ± 7 mmHg, 77 ± 6 mmHg) (p value = 0.012, 0.023). Regarding the OCTA VD metrics, there were no significant differences in VD between the caffeine and placebo groups, regardless of whether the scans were centered on the macula or ONH. Additionally, the comparison across different OCTA scan modalities, specifically the 3 × 3 mm and 6 × 6 mm scans, showed no discernible differences among groups. Conclusion: In conclusion, 200 mg of caffeine elevated blood pressure after 2 h but did not impact the retinal VD. This underscores the intricate relationship between caffeine, blood pressure, and retinal vascular dynamics, prompting further exploration of their implications for ocular health, especially in subjects with vascular disease.

Seated Elliptical Exercise, But Not Periodic Standing, Alleviates Sitting-Induced Changes to Arterial Wave Reflections.

Sedentary behavior may contribute to increased central wave reflection due to associated peripheral vasoconstriction, yet its impact on central hemodynamics and the mitigating effects of interventional strategies have not been thoroughly investigated. We tested whether standing or seated elliptical breaks alleviate the deleterious effects of prolonged sitting on central wave reflections. Eighteen healthy adults (9 9 females, 25 ± 3 yr) completed three 3-h protocols on separate days: uninterrupted sitting, sitting with periodic standing, and sitting with periodic seated elliptical activity. Central wave reflection, central pulse wave velocity, and lower-limb pulse wave velocity were measured before and after each intervention. Central relative wave reflection magnitude (RM) increased during sitting (0.31 ± 0.05 to 0.35 ± 0.05; P < 0.01) but did not change after standing (0.30 ± 0.05 to 0.32 ± 0.04; P = 0.19) or elliptical protocols (0.30 ± 0.05 to 0.30 ± 0.04; P > 0.99). The change in RM during prolonged sitting (ΔRM) was attenuated with elliptical activity (0.04 ± 0.05 vs 0.00 ± 0.03; P = 0.02) but not with periodic standing (0.04 ± 0.04 vs 0.02 ± 0.05; P = 0.54). In addition, augmentation index and central pulse wave velocity increased after sitting (both P < 0.01) and periodic standing (both P < 0.01) but were unchanged after elliptical activity. Lower limb pulse wave velocity did not change after sitting ( P = 0.73) or standing ( P = 0.21) but did decrease after elliptical activity ( P = 0.03). Prolonged sitting without interruptions increased central wave reflection, whereas elliptical but not standing interruptions were able to ameliorate multiple sitting-induced vascular consequences. More work is required to examine the long-term effectiveness of interruption strategies, as well as the optimal type, frequency, and duration for reducing vascular risk associated with sedentary behaviors.

Exaggerated Peripheral and Systemic Vasoconstriction During Trauma Recall in Posttraumatic Stress Disorder: A Co-Twin Control Study

BackgroundIndividuals with posttraumatic stress disorder (PTSD) face an increased risk of cardiovascular disease, but the mechanisms linking PTSD to cardiovascular disease remain incompletely understood. We used a co-twin control study design to test the hypothesis that individuals with PTSD exhibit augmented peripheral and systemic vasoconstriction during a personalized trauma recall task. MethodsIn 179 older male twins from the Vietnam Era Twin Registry, lifetime history of PTSD and current (last month) PTSD symptoms were assessed. Participants listened to neutral and personalized trauma scripts while peripheral vascular tone (Peripheral Arterial Tone ratio) and systemic vascular tone (e.g., total vascular conductance) were measured. Linear mixed-effect models were used to assess the within-pair relationship between PTSD and vascular tone indices. ResultsThe mean age of participants was 68 years, and 19% had a history of PTSD. For the Peripheral Arterial Tone ratio analysis, 32 twins were discordant for a history of PTSD, and 46 were discordant for current PTSD symptoms. Compared with their brothers without PTSD, during trauma recall, participants with a history of PTSD had greater increases in peripheral (β = −1.01, 95% CI [−1.72, −0.30]) and systemic (total vascular conductance: β = −1.12, 95% CI [−1.97, −0.27]) vasoconstriction after adjusting for cardiovascular risk factors. Associations persisted after adjusting for antidepressant medication use and heart rate and blood pressure during the tasks. Analysis of current PTSD symptom severity showed consistent results. ConclusionsPTSD is associated with exaggerated peripheral and systemic vasoconstrictor responses to traumatic stress reminders, which may contribute to elevated risk of cardiovascular disease.

Tom70-regulated mitochondrial biogenesis via TFAM improves hypoxia-induced dysfunction of pulmonary vascular endothelial cells and alleviates hypoxic pulmonary hypertension

BackgroundHypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. A large number of studies have shown that pulmonary vascular endothelial cells (PVECs) dysfunction plays an important role in the initiation and development stages of HPH, but the mechanism of PVECs dysfunction after hypoxia remains unclear. In this study, we explored the exact mechanism of PVECs dysfunction after hypoxia.MethodsIn vitro, we used primary cultured PVECs hypoxia model to mimic HPH injury. We detected the expressions of mitochondrial biogenesis markers, mitochondrial transcription factor A (TFAM) level inside mitochondria, mitochondrial quantity and function, and the components expressions of translocase of outer mitochondrial membrane (TOM) at 24 h after hypoxia. To explore the effects of Tom70 on mitochondrial biogenesis and functions of PVECs after hypoxia, Tom70 overexpression adenovirus was constructed, and the expressions of mitochondrial biogenesis markers, TFAM level inside mitochondria, mitochondrial quantity and function, and the functions of PVECs were detected. And in vivo, we used cre-dependent overexpression adenovirus of Tom70 in the Cdh5-CreERT2 mouse model of HPH to verify the role of upregulating PVECs Tom70 in improving HPH.ResultsHypoxia obviously increased the expressions of mitochondrial biogenesis markers for PGC-1α, NRF-1 and TFAM, but reduced the content of TFAM in mitochondria and the quantity and functions of mitochondria. In addition, only Tom70 expression among the TOM components was significantly decreased after hypoxia, and up-regulation of Tom70 significantly increased the content of TFAM in mitochondria of PVECs by transporting TFAM into mitochondria after hypoxia, enhanced the quantity and functions of mitochondria, improved the functions of PVECs, and ultimately alleviated HPH.ConclusionThe findings of present study demonstrated that hypoxia induced the decreased expression of Tom70 in PVECs, reduced the mitochondrial biogenesis-associated TFAM protein transporting into mitochondria, inhibited mitochondrial biogenesis, caused PVECs injury, and prompted the formation of HPH. However, up-regulation of Tom70 abolished the hypoxia-induced injurious effects on PVECs and alleviated HPH.

Acute response of astrocytes under rose bengal photoinduction‐mediated vascular injury

AbstractBackgroundCerebrovascular pathology, often found in autopsy confirmed Alzheimer’s disease (AD), is widely believed to exacerbate AD pathophysiology and complicate anti‐AD treatment strategies. Perivascular cells such as astrocytes maintain the microenvironment for proper brain cell function and vascular integrity. Early occurrence of cerebral small vessel disease and astrocyte reactivity could lower the threshold of neuronal disorders and AD. Studies of astrocyte and microvascular pathology and function in the brain have been limited and reaction of astrocytes to vascular damage has yet to be fully understood.MethodAAV‐Gfa‐EGFP or AAV‐Gfa‐GCaMP6 was injected into the barrel cortex of wild type mice followed by glass window installation. After 3 weeks recovery, rhodamine dextran was IV‐injected and intravital brain imaging through two‐photon microscopy was performed at pre‐ and post‐photoinduction. Photoactivation of IV‐injected Rose Bengal dye (RB) technique was used to create vascular pathology. ImageJ was used for data analysis and GraphPad prism was used for statistical analysis.ResultAfter photoinduction, green fluorescence intensity was increased in blood stream of both EGFP and GCaMP expressing brains. This result indicates a leakage of brain parenchyma component to blood stream. Astrocytic EGFP fluorescence intensity and astrocyte processes complexity were reduced after photoinduction in a time‐dependent manner. Interestingly, astrocyte calcium signaling was strikingly increased after photoinduction and returned back to the baseline at ∼1,000s post‐induction. The highest peak of astrocyte calcium signaling was located near a site of vascular damage, indicated by an increased in rhodamine fluorescence intensity in the brain parenchyma area. Astrocytic GCaMP intensity at the astrocyte endfeet surrounding small vasculature was increased, on the other hand, GCaMP intensity at the astrocyte processes are decreased in a time‐dependent manner. Consistently, we observed a reduction of vascular diameter after photoinduction in both EGFP and GCaMP expressing brains.ConclusionAcute vascular injury induced by rose bengal photoinduction altered astrocyte integrity and cellular signaling. This injury model resembles vascular constriction and hemorrhages found in human brain that could accelerate neurodegeneration and AD progression.

Nocturnal Autonomic and Vasoconstriction Parameters By Wearable Wrist Photoplethysmography Predict Intensity of Imminent Pain in Subjects with Sickle Cell Disease

Introduction: Sudden and unpredictable onset of pain is one of the biggest contributors to the morbidity of sickle cell disease (SCD), thought to occur due to obstruction of microvascular blood flow by rigid sickle-shaped red blood cells. Autonomic mediated vasoconstriction in the peripheral vasculature, with resulting decrease in tissue perfusion, is likely a triggering mechanism for the onset of vaso-occlusive pain, while the autonomic nervous system is also implicated in the pathogenesis of chronic neuropathic pain. Our analysis of 212 polysomnograms in SCD subjects showed that greater magnitude of nocturnal vasoconstriction (Mvasoc) is predictive of increased frequency of hospitalizations for vaso-occlusive pain crises (VOC) in the subsequent years (Chalacheva et al., Am J Hematol, 2020). In order to further develop this finding into a biomarker of more imminent pain, we monitored nocturnal photoplethysmography (PPG) at home with a wearable wristband device to measure vasoconstriction activity and heart rate variability, along with a daily electronic pain survey. Methods: 10 subjects with SCD were consented and underwent autonomic monitoring with a wristband device (Biostrap Inc) that uses an optical sensor to measure continuous PPG during sleep, with the raw PPG waveforms available from a cloud-based server. A unique biomarker (Mvasoc) was used to quantify the magnitude of vasoconstriction from the raw PPG signal, considering the frequency, magnitude, and duration of autonomic mediated spontaneous vasoconstrictions each night. Heart rate variability was derived from the pulse-to-pulse interval (PPI) of the PPG signal. Spectral indices of the PPI represent parasympathetic activity (high frequency power; HFP) and sympatho-vagal balance (Low to high Ratio; LHR = low frequency power(LFP)/HFP). Subjects concurrently documented daily pain incidence using an electronic text-based REDCap survey, with pain intensity measured on a scale of 1-10 if experiencing pain. Daily stress levels were also recorded on a scale of 1-10. Multivariate regression analysis was performed. Results: The subjects had a mean age of 25 years (range 14- 40 years) with an average hemoglobin of 8.8 g/dl . A total of 68 usable nocturnal PPG recordings were made (3-16 nights per subject). Therewere 25 incidents of pain on the day following autonomic monitoring with Biostrap, with the pain intensity ranging from 3-8. Multivariate analysis of nocturnal autonomic and vasoconstriction parameters revealed that a lower HFP ( p =0.0002) and a higher Mvasoc ( p=0.02) both preceded a higher intensity of pain the following day (Table 1). These results are consistent with a greater parasympathetic withdrawal and a higher magnitude of peripheral vasoconstriction predicting higher intensity of imminent pain. Age, gender, hemoglobin, stress levels and LHR were not predictive of pain the following day. Conclusion: Augmented nocturnal vasoconstriction and parasympathetic withdrawal noted prior to high intensity of pain imply that dysautonomia, with attendant changes in peripheral perfusion, has a significant role in pathogenesis of pain in SCD. Furthermore, autonomic vasoreactivity parameters were not significantly altered on the night after pain onset suggesting that the dysautonomia precedes pain. These results support the possibility of employing indices of nocturnal autonomic vasoreactivity as a predictive biomarker for imminent pain in SCD and provides a potential window for therapeutic intervention. This pilot study demonstrates the successful use of a wearable device PPG to remotely monitor nocturnal autonomic vasoreactivity and the ability to objectively quantify peripheral vasoconstriction responses. These findings will need to be applied in a larger cohort of SCD subjects with longer term monitoring for further validation and development of autonomic vasoreactivity as a predictive tool for pain in SCD.

Subjective perceptions of 8, 11 and 14°C chemotherapy liquid cooled gloves and socks

We investigated the effects of peripheral cooling using chemotherapy gloves and socks at three cooling temperatures on subjective perceptions. The hands and feet were cooled with 8, 11, and 14°C by water-perfused gloves or socks. Nine females participated in six experimental conditions: hands or feet cooling at 8, 11, and 14°C. The heat was extracted at 3.8, 5.4, and 7.7 kJ·min1 via the gloves and at 4.1, 6.0, and 9.0 kJ·min-1 via the socks. While the results showed that overall subjective perceptions did not differ among the three temperatures (~ 9.0 kJ·min-1), there were significant differences in local thermal comfort, pain sensation, and pain discomfort among the three cooling temperatures (P < 0.05). When cooling the hands or feet at 8, 11 or 14°C, subjects felt ‘cold’ or ‘cool’, on average, at the end of 60-min cooling with no significant differences among the three temperatures, whereas subjects felt more uncomfortable at 8°C than 14°C for cooling either the hands or feet (P < 0.05). Subjects felt more pain at 8°C than 14°C cooling for both hands and feet. These results indicate that the 8°C cooling for 60 min might cause uncomfortable pain sensation, especially for cold-vulnerable individuals. We recommend 1) a cooling bout of less than 60 min, 2) a cooling temperature higher than 8oC when cooling the hands or feet, and 3) a higher temperature for the feet when the hands are simultaneously cooled. However, the present results on subjective perceptions should be interpreted with peripheral vasoconstriction of fingers and toes while cooling.

Physiological Responses during Prolonged Immersed Static Apnea in Well-Trained Apneists

Breath-hold diving has been traditionally practiced for professional and recreational reasons and has recently emerged as a competitive sport. The physiological response during breath-holding, also known as diving response, consists mainly of bradycardia and peripheral vasoconstriction. Elite apneists can suppress the urge to breathe, sustain greater arterial desaturation and develop pronounced bradycardia, thus accomplishing impressively long breath-hold times. This study explored physiological responses during static apnea and their association with apnea duration in breath-hold divers with high physiological adaptations acquired from long-term apnea training. Nine well-trained competitive divers held their breath for as long as possible while floating motionlessly in a swimming pool (26–27 °C), simulating an actual “static apnea competition”. Long apnea durations (302 ± 60 s) as well as severe oxygen desaturation (minSaO2 46 ± 11%) and bradycardia (minHR 49 ± 8 bpm) were achieved. Apnea duration was positively correlated with forced vital capacity (r = 0.771) and apnea duration until initiation of desaturation (r = 0.736) and negatively correlated with minSaO2 (r = −0.672) (p &lt; 0.05). Moreover, minHR during apnea was correlated with pre-apneic hemoglobin concentration (r = 0.685) (p &lt; 0.05). The prolonged apnea durations achieved by the well-trained divers in this study, while performing maximum immersed static apnea under competitive simulated conditions, were related to their high lung volumes and their delayed and profound O2 desaturation, whereas their bradycardic response was not a decisive factor.

Specific role of NAD+ biosynthesis reduction mediated mitochondrial dysfunction in vascular endothelial injury induced by chronic intermittent hypoxia.

Cardiovascular diseases (CVD) are prevalent among those with obstructive sleep apnea (OSA) and are the leading cause of death in these individuals. However, due to clinical confounders, the mechanism by which OSA induces CVD is still unclear. Previous studies have shown that chronic intermittent hypoxia (CIH) and high cholesterol diet (HCD) induce distinct characteristics of atherosclerotic plaques, highlighting the specific mechanisms involved in CIH-induced vascular endothelial injury. This study aims to investigate whether nicotinamide adenine dinucleotide (NAD+) biosynthesis reduction-mediated mitochondrial dysfunction is responsible for vascular endothelial injury induced by CIH and to elucidate its specific role in this process. Models were established to stimulate human umbilical vein endothelial cells (HUVECs) with CIH and oxidized low-density lipoprotein (ox-LDL), and the NAD+ biosynthesis-related indicators, such as NAD+ levels and nicotinamide phosphoribosyltransferase (NAMPT) enzyme activity, were measured in this model. Additionally, interventions were performed by supplementing NAD+ levels with nicotinamide mononucleotide (NMN), inhibiting NAD+ synthesis with FK866, and evaluating mitochondrial function, oxidative stress status, vascular constriction and dilation function, and endothelial adhesion function in these models. A comparative study was conducted to assess the effects of these interventions. We found that under CIH conditions, NAMPT enzyme activity was inhibited, leading to a reduction in NAD+ biosynthesis and a decrease in NAD+/NADH ratio. At the same time, CIH caused mitochondrial dysfunction in HUVECs, including a decrease in adenosine triphosphate (ATP) content and mitochondrial membrane potential, as well as the activity of respiratory chain complex I and III, induced an increase in oxidative stress levels in endothelial cells, impaired vascular constriction and dilation function, and significantly increased expression of adhesion factors. The impact of CIH on endothelial cell-related mitochondrial function and endothelial function was restored by supplementing NMN. Although ox-LDL also causes multi-level endothelial injury, it does not involve the NAD+ pathway, as there were no significant changes in the related indicators, and the impaired endothelial function under ox-LDL conditions was not restored by supplementing NMN. CIH-induced vascular endothelial injury may be associated with NAD+ biosynthesis reduction-mediated mitochondrial dysfunction. Supplementing NAD+ precursors to increase its levels may be a potential intervention to ameliorate CIH-induced vascular endothelial injury, while it does not have a significant effect on endothelial injury caused by ox-LDL.