Microsurgery and vasospasms: Spasms' predictive factors during harvesting.

BACKGROUND: Vasospasm (VS) in microsurgery is a source of surgical complications, repeat operations, stress for the patient and the surgical team, as well as increased length of stay. Various risk factors have been identified but knowledge regarding the implicated mechanism remains limited. HYPOTHESIS: Our objective was to determine if the harvesting conditions for microsurgical toe transfers could increase the risk of VS. Our secondary objective was to determine the correlation between VS occurrence before flap division, and the occurrence of vascular complications after completion of vascular anastomoses. PATIENTS AND METHODS: Primary endpoints were the existence of locoregional anaesthesia of the lower limb, the Gilbert classification, the nature of the graft taken from the foot, the characteristics of the patients and smoking status. Our secondary endpoints were the presence of secondary VS or microsurgical failure. This series consists of 14 toe transfers over a 30-month period. Primary VS was defined as occurring prior to flap division, while secondary VS occurred after transfer. RESULTS: In this series, we identified 4 cases of primary VS. The average age of the operated population was 30.6 ± 11.2 years (16-58). The patients who presented with primary VS had a mean age of 35.3 ± 16.2 years (21-58), with no statistical difference with the other group (p = 0.54). There was a statistically significant difference between the absence of locoregional anaesthesia and the occurrence of primary VS in toe transfer (p = 0.0008). Microsurgical failure occurred in 1 case. This failure was linked to the presence of a primary VS. Gilbert's classification and type of graft were not predictive of VS (p = 0.15 and p = 0.08, respectively). The occurrence of secondary VS was statistically linked to the occurrence of primary VS (p = 0.009). DISCUSSION: The occurrence of VS remains unpredictable and the effectiveness of available treatments is debated in the literature. Faced with the failure of curative treatments, this study aimed to determine predictive factors for VS. The existence of secondary VS, when prolonged and non-responsive to conventional measures, can lead to anastomotic revision. Performing locoregional anaesthesia on the lower limb makes it possible to effectively combat the occurrence of VS. The absence of primary VS was correlated with an absence of secondary VS and an absence of microsurgical failure. In addition to controlling vasospasm, regional anaesthesia provides effective analgesia at the harvesting site. LEVEL OF EVIDENCE: IV.

Temperature-responsive hydrogel-grafted vessel-on-a-chip: Exploring cold-induced endothelial injury.

Cold-induced vasoconstriction is a significant contributor that leads to chilblains and hypothermia in humans. However, current animal models have limitations in replicating cold-induced acral injury due to their low sensitivity to cold. Moreover, existing in vitro vascular chips composed of endothelial cells and perfusion systems lack temperature responsiveness, failing to simulate the vasoconstriction observed under cold stress. This study presents a novel approach where a microfluidic bioreactor of vessel-on-a-chip was developed by grafting the inner microchannel surface of polydimethylsiloxane with a thermosensitive hydrogel skin composed of N-isopropyl acrylamide and gelatin methacrylamide. With a lower critical solution temperature set at 30°C, the gel layer exhibited swelling at low temperatures, reducing the flow rate inside the channel by 10% when the temperature dropped from 37°C to 4°C. This well mimicked the blood stasis observed in capillary vessels in vivo. The vessel-on-a-chip was further constructed by culturing endothelial cells on the surface of the thermosensitive hydrogel layer, and a perfused medium was introduced to the cells to provide a physiological shear stress. Notably, cold stimulation of the vessel-on-a-chip led to cell necrosis, mitochondrial membrane potential (ΔΨm) collapse, cytoskeleton disaggregation, and increased levels of reactive oxygen species. In contrast, the static culture of endothelial cells showed limited response to cold exposure. By faithfully replicating cold-induced endothelial injury, this groundbreaking thermosensitive vessel-on-a-chip technology offers promising advancements in the study of cold-induced cardiovascular diseases, including pathogenesis and therapeutic drug screening.

Adrenergic Urticaria: An Updated Review.

It can be difficult to delineate the cause of urticarial eruptions, and in chronic cases, it can be a challenging condition to effectively treat. Several forms of urticarial eruptions are well documented and established. Our review focuses on a form of urticaria that is less commonly reported: adrenergic urticaria. In this review, we aim to consolidate the literature in the hopes that this urticarial subtype is considered in urticarial differentials, as well as highlight potential gaps in the research and future directions in treatment options.

Downregulation of stromal interaction molecule-1 is implicated in the age-associated vasoconstriction dysfunction of aorta, intrarenal, and coronary arteries.

The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-ß-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway.

Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea.

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima-media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.

Pharmacological Gq inhibition induces strong pulmonary vasorelaxation and reverses pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a life-threatening disease with limited survival. Herein, we propose the pharmacological inhibition of Gq proteins as a novel concept to counteract pulmonary vasoconstriction and proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in PAH. We demonstrate that the specific pan-Gq inhibitor FR900359 (FR) induced a strong vasorelaxation in large and small pulmonary arteries in mouse, pig, and human subjects ex vivo. Vasorelaxation by FR proved at least as potent as the currently used triple therapy. We also provide in vivo evidence that local pulmonary application of FR prevented right ventricular systolic pressure increase in healthy mice as well as in mice suffering from hypoxia (Hx)-induced pulmonary hypertension (PH). In addition, we demonstrate that chronic application of FR prevented and also reversed Sugen (Su)Hx-induced PH in mice. We also demonstrate that Gq inhibition reduces proliferation and migration of PASMCs in vitro. Thus, our work illustrates a dominant role of Gq proteins for pulmonary vasoconstriction as well as remodeling and proposes direct Gq inhibition as a powerful pharmacological strategy in PH.

Neuropsychological aspects of reversible cerebral vasoconstriction syndrome.

Despite the increasing knowledge in the past years, only minimal attention has been directed to the neuropsychological aspects and the prevalence of cognitive impairment associated with reversible cerebral vasoconstriction syndrome (RCVS). Objective: To describe the frequency and expand the understanding of cognitive dysfunction in RCVS. Methods: The neuropsychological evaluation was performed using a battery consisting of specific neuropsychological instruments that were administered to patients diagnosed with RCVS. A triage was conducted to exclude other potential causes of cognitive impairment. Performance on the tests was treated as a categorical variable, and a cutoff of -1.5 Z-score was adopted to indicate impaired performance. Results: Seven patients diagnosed with RCVS were evaluated, all of whom had a bachelor's degree and normal score in the Mini-Mental State Examination. The average time between diagnosis and neuropsychological evaluation was 1.8 years. Among the patients, 85.6% (n=6) exhibited performance below that of the normal population in at least two of the administered tests. Specifically, 71.4% (n=5) showed alterations in tests from the Psychological Battery for Attention Assessment, with impairment observed in concentrated (n=1), divided (n=3), or alternating (n=4) attention. Furthermore, 28.6% (n=2) demonstrated impairments in the Phonological Verbal Fluency Task, another 28.6% (n=2) exhibited difficulties copying elements of the Rey Complex Figure, and 14.3% (n=1) displayed lower performance in the Five-Digit test, all indicating executive dysfunction. Conclusion: This study provides evidence that cognitive impairment associated with RCVS is more prevalent than previously believed and has not received sufficient attention. Specifically, attention and executive functions are the cognitive domains most significantly impacted by RCVS.

Apesar do crescente conhecimento nos últimos anos, pouca atenção tem sido direcionada aos aspectos neuropsicológicos e à prevalência de declínio cognitivo associado à Síndrome de Vasoconstrição Cerebral Reversível (SVCR). Objetivo: Descrever a frequência e expandir o entendimento da disfunção cognitiva associada à SVCR. Métodos: A avaliação neuropsicológica foi realizada por meio de uma bateria composta de instrumentos neuropsicológicos específicos, que foram aplicados aos pacientes com SVCR. Uma triagem foi realizada para excluir outras potenciais causas de declínio cognitivo. O desempenho nos testes foi considerado como variável categórica, e o corte de −1,5 escore z foi adotado para indicar desempenho comprometido. Resultados: Sete pacientes com diagnóstico de SVCR foram avaliados, os quais tinham todos nível de ensino superior e pontuação normal no Miniexame do Estado Mental. A média de tempo entre o diagnóstico e a avaliação neuropsicológica foi de 1,8 ano. Dentre os pacientes, 85,6%(n=6) apresentaram desempenho comprometido em pelo menos dois dos testes aplicados. Especificamente, 71,4% (n=5) apresentaram alterações nos testes da Bateria Psicológica para Avaliação da Atenção, com comprometimento observado nas atenções concentrada (n=1), dividida (n=3), ou alternada (n=4). Além disso, 28,6% (n=2) demonstraram comprometimento na Fluência Verbal Fonológica, 28,6% (n=2) exibiram dificuldades na cópia da Figura Complexa de Rey e um paciente obteve desempenho alterado no Teste dos Cinco Dígitos, todos indicando disfunção executiva. Conclusão: Este estudo fornece evidência de que o declínio cognitivo associado à SVCR é mais prevalente do que se acreditava anteriormente. Especialmente, os domínios mais significativamente comprometidos foram a atenção e as funções executivas.

Foot Drop Following a Popliteal Sciatic Nerve Block with Ropivacaine, A Case Report and Literature Review.

Although peripheral nerve blocks are deemed very safe, a significant number of patients for whom this anesthetic technique may be particularly appealing to apply may present with preexisting peripheral neuropathies, putting them at risk for further nerve damage. We present a case with a 74-year-old male with several risk factors for peripheral neuropathy who developed a foot drop following a popliteal sciatic nerve block with ropivacaine. We suggest that the vasoconstrictive properties of ropivacaine may have contributed to a preexisting neuronal ischemia, thus further damaging an already compromised nerve.

LPA-Induced Thromboxane A2-Mediated Vasoconstriction Is Limited to Poly-Unsaturated Molecular Species in Mouse Aortas.

We have previously reported that, in aortic rings, 18:1 lysophosphatidic acid (LPA) can induce both vasodilation and vasoconstriction depending on the integrity of the endothelium. The predominant molecular species generated in blood serum are poly-unsaturated LPA species, yet the vascular effects of these species are largely unexplored. We aimed to compare the vasoactive effects of seven naturally occurring LPA species in order to elucidate their potential pathophysiological role in vasculopathies. Vascular tone was measured using myography, and thromboxane A2 (TXA2) release was detected by ELISA in C57Bl/6 mouse aortas. The Ca2+-responses to LPA-stimulated primary isolated endothelial cells were measured by Fluo-4 AM imaging. Our results indicate that saturated molecular species of LPA elicit no significant effect on the vascular tone of the aorta. In contrast, all 18 unsaturated carbon-containing (C18) LPAs (18:1, 18:2, 18:3) were effective, with 18:1 LPA being the most potent. However, following inhibition of cyclooxygenase (COX), these LPAs induced similar vasorelaxation, primarily indicating that the vasoconstrictor potency differed among these species. Indeed, C18 LPA evoked a similar Ca2+-signal in endothelial cells, whereas in endothelium-denuded aortas, the constrictor activity increased with the level of unsaturation, correlating with TXA2 release in intact aortas. COX inhibition abolished TXA2 release, and the C18 LPA induced vasoconstriction. In conclusion, polyunsaturated LPA have markedly increased TXA2-releasing and vasoconstrictor capacity, implying potential pathophysiological consequences in vasculopathies.

Pathophysiologic Vasodilation in Cardiogenic Shock and Its Impact on Mortality.

BACKGROUND: Cardiogenic shock (CS) mortality remains near 40%. In addition to inadequate cardiac output, patients with severe CS may exhibit vasodilation. We aimed to examine the prevalence and consequences of vasodilation in CS. METHODS: We analyzed all patients hospitalized at a CS referral center who were diagnosed with CS stages B to E and did not have concurrent sepsis or recent cardiac surgery. Vasodilation was defined by lower systemic vascular resistance (SVR), higher norepinephrine equivalent dose, or a blunted SVR response to pressors. Threshold SVR values were determined by their relation to 14-day mortality in spline models. The primary outcome was death within 14 days of CS onset in multivariable-adjusted Cox models. RESULTS: This study included 713 patients with a mean age of 60 years and 27% females; 14-day mortality was 28%, and 38% were vasodilated. The median SVR was 1308 dynes•s•cm-5 (interquartile range, 870-1652), median norepinephrine equivalent was 0.11 µg/kg per minute (interquartile range, 0-0.2), and 28% had a blunted pressor response. Each 100-dynes•s•cm-5 decrease in SVR below 800 was associated with 20% higher mortality (adjusted hazard ratio, 1.23; P=0.004). Each 0.1-µg/kg per minute increase in norepinephrine equivalent dose was associated with 15% higher mortality (adjusted hazard ratio, 1.12; P<0.001). A blunted pressor response was associated with a nearly 2-fold mortality increase (adjusted hazard ratio, 1.74; P=0.003). CONCLUSIONS: Pathophysiologic vasodilation is prevalent in CS and independently associated with an increased risk of death. CS vasodilation can be identified by SVR <800 dynes•s•cm-5, high doses of pressors, or a blunted SVR response to pressors. Additional studies exploring mechanisms and treatments for CS vasodilation are needed.

Radiological Findings in Reversible Cerebral Vasoconstriction Syndrome: A Systematic Review of Literature.

Reversible cerebral vasoconstriction syndrome (RCVS) poses a complex neurological challenge characterized by sudden, severe headaches and multifocal cerebral vasoconstriction. While our understanding of its clinical aspects and underlying mechanisms has advanced, the focus of investigation remains on radiological manifestations. This systematic review aims to comprehensively analyze the existing literature on radiological findings in RCVS, synthesizing evidence from diverse imaging modalities to enhance the understanding of imaging features associated with the syndrome. Accurate diagnosis based on radiological findings is pivotal for initiating appropriate management and preventing complications. Specific markers may facilitate the differentiation of RCVS from other conditions, thereby enhancing patient care. This review explores a wide range of radiological presentations, from vasoconstriction to infarctions and hemorrhages, thereby refining diagnostic criteria and guiding clinical practice. By consolidating current knowledge, the review sheds light on areas of consensus, controversies, and gaps, with the aim of serving as a comprehensive resource for evidence-based decision-making.

Mapping the unicellular transcriptome of the ascending thoracic aorta to changes in mechanosensing and mechanoadaptation during aging.

Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.

Oxygen fluctuations in the brain and periphery induced by intravenous fentanyl: effects of dose and drug experience.

Fentanyl is the leading contributor to drug overdose deaths in the United States. Its potency, rapid onset of action, and lack of effective reversal treatment make the drug much more lethal than other opioids. Although it is understood that fentanyl is dangerous at higher doses, the literature surrounding fentanyl's physiological effects remains contradictory at lower doses. To explore this discrepancy, we designed a study incorporating electrochemical assessment of oxygen in the brain (nucleus accumbens) and subcutaneous space, multisite thermorecording (brain, skin, muscle), and locomotor activity at varying doses of fentanyl (1.0, 3.0, 10, 30, and 90 µg/kg) in rats. In the nucleus accumbens, lower doses of fentanyl (3.0 and 10 µg/kg) led to an increase in oxygen levels while higher doses (30 and 90 µg/kg) led to a biphasic pattern, with an initial dose-dependent decrease followed by an increase. In the subcutaneous space, oxygen decreases started to appear at relatively lower doses (>3 µg/kg), had shorter onset latencies, and were stronger and prolonged. In the temperature experiment, lower doses of fentanyl (1.0, 3.0, and 10 µg/kg) led to an increase in brain, skin, and muscle temperatures, while higher doses (30 and 90 µg/kg) resulted in a dose-dependent biphasic temperature change, with an increase followed by a prolonged decrease. We also compared oxygen and temperature responses induced by fentanyl over six consecutive days and found no evidence of tolerance in both parameters. In conclusion, we report that fentanyl's effects are highly dose-dependent, drawing attention to the importance of better characterization to adequately respond in emergent cases of illicit fentanyl misuse.NEW & NOTEWORTHY By using electrochemical oxygen sensors in freely moving rats, we show that intravenous fentanyl induces opposite changes in brain oxygen at varying doses, increasing at lower doses (<10 µg/kg) and inducing a biphasic response, decrease followed by increase, at higher doses (>10-90 µg/kg). In contrast, fentanyl-induced dose-dependent oxygen decreases in the subcutaneous space. We consider the mechanisms underlying distinct oxygen responses in the brain and periphery and discuss naloxone's role in alleviating fentanyl-induced brain hypoxia.

Effect of lipid emulsion on vasoconstriction induced by epinephrine or norepinephrine in isolated rat aorta.

Background: Epinephrine (EPI) or norepinephrine (NOR) is widely used to treat cardiovascular collapse during lipid emulsion (LE) resuscitation for drug toxicity. However, the effect of LE on the vasoconstriction caused by EPI or NOR remains unknown. The purpose of this study was to examine the effect of an LE (Intralipid) on the vasoconstriction caused by EPI and NOR in isolated rat aorta. Methods: The effect of LE on the vasoconstriction caused by EPI or NOR in isolated rat aorta was examined. Additionally, the effect of LE on the calcium increase caused by EPI or NOR was investigated. The distribution constant (KD: lipid to aqueous phase) of EPI or NOR between a LE (1%) and an aqueous phase was determined. Results: LE (1 and 2%) did not significantly alter vasoconstriction caused by EPI or NOR in isolated endothelium-intact aorta. Moreover, the LE did not significantly alter the increased calcium level caused by EPI or NOR. The log KD of EPI in the LE (1%) was -0.71, -0.99, and -1.00 at 20, 50, and 100 mM ionic strength, respectively. The log KD of NOR in the LE (1%) was -1.22, -1.25, and -0.96 at 20, 50, and 100 mM ionic strength, respectively. Conclusions: Taken together, the Intralipid emulsion did not alter vasoconstriction induced by EPI or NOR that seems to be due to the hydrophilicity of EPI or NOR, leading to sustained hemodynamic support produced by EPI or NOR used during LE resuscitation.

Cerebrospinal Fluid Proteome Map Reveals Molecular Signatures of Reversible Cerebral Vasoconstriction Syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n = 21) compared to the age- and sex-matched controls (n  = 20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations.

Prenatal High-Sucrose Diet Induced Vascular Dysfunction of Renal Interlobar Arteries in the Offspring via PPARγ-RXRg-ROS/Akt Signaling.

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.

Sex-based difference in selected stroke etiologies: cerebral dural sinus venous thrombosis, reversible cerebral vasoconstriction syndrome, dissection, migraine, pregnancy/puerperium/OC use.

Females are at higher risk than males for a multitude of cerebrovascular conditions, both common and rare; partially resulting from a complex interplay between differing process involving genetics, hormonal influences, common cerebrovascular risk factors among others. Specific topics including cervical artery dissection, cerebral dural sinus venous thrombosis, reversible cerebral vasoconstriction syndrome, migraine, along with these disorders in the setting of pregnancy, puerperium and oral contraceptive utilization. Epidemiology, pathophysiology, presentation, basics of management and outcomes are presented, with sex differences throughout.

[Effects of Rhodiola rosea injection on intrapulmonary shunt and blood IL-6 and TNF-α levels during single lung ventilation in patients undergoing radical resection of esophageal cancer].

OBJECTIVE: To explore the effects of Rhodiola rosea injection on pulmonary shunt and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during single lung ventilation in patients undergoing radical resection of esophageal cancer. METHODS: Forty-six patients undergoing radical operation for esophageal cancer were randomized equally into control group and Rhodiola rosea injection group. In the Rhodiola group, 10 mL of Rhodiola rosea injection was added into 250 mL of normal saline or 5% glucose solution for slow intravenous infusion, and normal saline of the same volume was used in the control group after the patients entered the operation room. At T0, T1 and T3, PaO2 of the patient was recorded and 2 mL of deep venous blood was collected for determination of serum TNF-α and IL-6 levels. The incidence of postoperative atelectasis of the patients was recorded. RESULTS: Compared with those in the control group, the patients receiving Rhodiola rosea injection had significantly higher PaO2 and Qs/Qt at T1 and T2 (P<0.05) and lower serum IL-6 and TNF-α levels at T3 (P<0.05). No significant difference in the incidence of postoperative atelectasis was observed between the two groups (P>0.05). CONCLUSION: Rhodiola rosea injection before anesthesia induction can reduce intrapulmonary shunt during single lung ventilation, improve oxygenation, reduce serum IL-6 and TNF-α levels, and alleviate intraoperative lung injury in patients undergoing radical resection of esophageal cancer.

The Enigma of Norbormide, a Rattus-Selective Toxicant.

Norbormide (NRB) is a Rattus-selective toxicant, which was serendipitously discovered in 1964 and formerly marketed as an eco-friendly rodenticide that was deemed harmless to non-Rattus species. However, due to inconsistent efficacy and the emergence of second-generation anticoagulants, its usage declined, with registration lapsing in 2003. NRBs' lethal action in rats entails irreversible vasoconstriction of peripheral arteries, likely inducing cardiac damage: however, the precise chain of events leading to fatality and the target organs involved remain elusive. This unique contractile effect is exclusive to rat arteries and is induced solely by the endo isomers of NRB, hinting at a specific receptor involvement. Understanding NRB's mechanism of action is crucial for developing species-selective toxicants as alternatives to the broad-spectrum ones currently in use. Recent research efforts have focused on elucidating its cellular mechanisms and sites of action using novel NRB derivatives. The key findings are as follows: NRB selectively opens the rat mitochondrial permeability transition pore, which may be a factor that contributes to its lethal effect; it inhibits rat vascular KATP channels, which potentially controls its Rattus-selective vasoconstricting activity; and it possesses intracellular binding sites in both sensitive and insensitive cells, as revealed by fluorescent derivatives. These studies have led to the development of a prodrug with enhanced pharmacokinetic and toxicological profiles, which is currently undergoing registration as a novel efficacious eco-sustainable Rattus-selective toxicant. The NRB-fluorescent derivatives also show promise as non-toxic probes for intracellular organelle labelling. This review documents in more detail these developments and their implications.

How selective antagonists and genetic modification have helped characterise the expression and functions of vascular P2Y receptors.

Vascular P2Y receptors mediate many effects, but the role of individual subtypes is often unclear. Here we discuss how subtype-selective antagonists and receptor knockout/knockdown have helped identify these roles in numerous species and vessels. P2Y1 receptor-mediated vasoconstriction and endothelium-dependent vasodilation have been characterised using the selective antagonists, MRS2179 and MRS2216, whilst AR-C118925XX, a P2Y2 receptor antagonist, reduced endothelium-dependent relaxation, and signalling evoked by UTP or fluid shear stress. P2Y2 receptor knockdown reduced endothelial signalling and endothelial P2Y2 receptor knockout produced hypertensive mice and abolished vasodilation elicited by an increase in flow. UTP-evoked vasoconstriction was also blocked by AR-C118925XX, but the effects of P2Y2 receptor knockout were complex. No P2Y4 receptor antagonists are available and P2Y4 knockout did not affect the vascular actions of UTP and UDP. The P2Y6 receptor antagonist, MRS2578, identified endothelial P2Y6 receptors mediating vasodilation, but receptor knockout had complex effects. MRS2578 also inhibited, and P2Y6 knockout abolished, contractions evoked by UDP. P2Y6 receptors contribute to the myogenic tone induced by a stepped increase in vascular perfusion pressure and possibly to the development of atherosclerosis. The P2Y11 receptor antagonists, NF157 and NF340, inhibited ATP-evoked signalling in human endothelial cells. Vasoconstriction mediated by P2Y12/P2Y13 and P2Y14 receptors was characterised using the antagonists, cangrelor, ticagrelor, AR-C67085 and MRS2211 or PPTN respectively. This has yet to be backed up by receptor knockout experiments. Thus, subtype-selective antagonists and receptor knockout/knockdown have helped identify which P2Y subtypes are functionally expressed in vascular smooth muscle and endothelial cells and the effects that they mediate.