-
Anesthesiology May 2024Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models....
BACKGROUND
Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain oedema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid (CSF) flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial CSF-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, we studied the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences - vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane (ISO).
METHODS
End-tidal carbon dioxide (EtCO2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (EtCO2 80 mmHg) or hyperventilation (EtCO2 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 minutes in 1) normoventilated (EtCO2 40 mmHg) K/DEX, 2) normoventilated ISO, 3) hypercapnic K/DEX, and 4) hyperventilated ISO groups using dynamic whole-body single-photon emission tomography. CSF volume changes were assessed with magnetic resonance imaging.
RESULTS
Under normoventilation, cortical CSF tracer perfusion, perivascular space size around middle cerebral arteries (MCAs), and intracranial CSF volume were higher under K/DEX compared with ISO (cortical Cmax ratio 2.33 [95% CI 1.35 to 4.04], perivascular size ratio 2.20 [95% CI 1.09 to 4.45], and intracranial CSF volume ratio 1.90 [95% CI 1.33 to 2.71]). Under ISO, tracer was directed to systemic circulation. Under K/DEX, the intracranial tracer distribution and CSF volume were uninfluenced by hypercapnia compared with normoventilation. Intracranial CSF tracer distribution was unaffected by hyperventilation under ISO despite a 28% increase in CSF volume around MCAs.
CONCLUSIONS
K/DEX and ISO overrode carbon dioxide as a regulator of CSF flow. K/DEX could be used to preserve CSF space and dynamics in hypercapnia whereas hyperventilation was insufficient to increase cerebral CSF perfusion under ISO.
PubMed: 38787687
DOI: 10.1097/ALN.0000000000005039 -
Biomolecules May 2024Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare subtype of group 1 pulmonary hypertension (PH) diseases, characterized by high pulmonary artery pressure leading to right ventricular dysfunction and potential life-threatening consequences. PAH involves complex mechanisms: vasoconstriction, vascular remodeling, endothelial dysfunction, inflammation, oxidative stress, fibrosis, RV remodeling, cellular hypoxia, metabolic imbalance, and thrombosis. These mechanisms are mediated by several pathways, involving molecules like nitric oxide and prostacyclin. PAH diagnosis requires clinical evaluation and right heart catheterization, confirming a value of mPAP ≥ 20 mmHg at rest and often elevated pulmonary vascular resistance (PVR). Even if an early and accurate diagnosis is crucial, PAH still lacks effective biomarkers to assist in its diagnosis and prognosis. Biomarkers could contribute to arousing clinical suspicion and serve for prognosis prediction, risk stratification, and dynamic monitoring in patients with PAH. The aim of the present review is to report the main novelties on new possible biomarkers for the diagnosis, prognosis, and treatment monitoring of PAH.
Topics: Humans; Biomarkers; Pulmonary Arterial Hypertension; Prognosis; Hypertension, Pulmonary; Oxidative Stress
PubMed: 38785959
DOI: 10.3390/biom14050552 -
American Journal of Hypertension May 2024Extracellular volume (ECV) overload and endothelial cell dysfunction (ECD) are independent risk factors for mortality in hemodialysis patients. Endothelin-1 (ET-1), an...
INTRODUCTION
Extracellular volume (ECV) overload and endothelial cell dysfunction (ECD) are independent risk factors for mortality in hemodialysis patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in hemodialysis patients and heart failure patients without kidney disease. We hypothesized there would be associations between ET-1 and ECV overload assessed with bioimpedance spectroscopy (BIS) in hypertensive hemodialysis patients.
METHODS
We obtained pre-HD plasma ET-1, ECV/weight (using multi-frequency BIS), pre-HD hemodynamic measurements, and ambulatory blood pressure (BP) in a cohort of HD patients. Following appropriate transformations, we conducted correlation and linear regression analyses to identify associations between ET-1 and ECV overload. We further explored associations between ET-1 and total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP.
RESULTS
Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/mL. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) L/kg, 3161 (2711-3642) dynes*sec/cm-5/m2, 2.92 (0.6) L/min/m2, and 143 (14) mmHg, respectively. After reciprocal transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r=0.3, p=.01), log-transformed TPRI (r=-0.3, p=.006), CI (r=0.3, p=.009) and ambulatory BP (r=-0.3, p=.02). Controlling for demographic variables, these associations persisted in linear regression analysis (β=0.15, p=.002; β=-0.8, p=.002; β=0.2, p=.002; β=-19, p=.03).
CONCLUSIONS
In hypertensive HD patients, ECV overload is associated with ET-1. ET-1 is associated with higher TPRI and lower CI before dialysis and higher ambulatory BP. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload.
PubMed: 38779972
DOI: 10.1093/ajh/hpae060 -
BMC Cardiovascular Disorders May 2024Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis...
INTRODUCTION
Surgery remains the primary treatment modality for thymic carcinoma, with adjuvant radiotherapy being recommended to effectively mitigate local recurrence and metastasis rates subsequent to incomplete or complete resection. Chemoradiotherapy has the potential to induce coronary artery occlusion, thereby potentially impacting patients' long-term survival rates. The existing literature currently lacks comprehensive research on the lesion characteristics of coronary artery injury resulting from chemoradiotherapy.
CASE PRESENTATION
The male patient, aged 55, was admitted to the hospital due to recurrent chest tightness and pain persisting for one week. Notably, the patient had previously undergone curative resection surgery for thymic carcinoma seven years ago. After the surgical procedure, the patient underwent a course of adjuvant chemotherapy comprising docetaxel and platinum. 11 months later, imaging examination diagnosed tumor recurrence, and concurrent chemoradiotherapy was administered at a total dose of 62 Gy/31F for planning gross target volume (PGTV) and 54 Gy/31F for planning target volume (PTV) with 2 cycles of paclitaxel and cisplatin. Re-admission of the patient occurred after a 7-year interval subsequent to the completion of concurrent chemoradiotherapy, leading to a subsequent diagnosis of acute non-ST segment elevation myocardial infarction. Following administration of antiplatelet, anticoagulant, and anti-myocardial ischemia therapy, coronary angiography revealed the presence of a bifurcation lesion at the distal end of the left main trunk. Intravascular ultrasound (IVUS) examination demonstrated significant negative remodeling of both the main trunk and its branches at the bifurcation site, characterized by minimal atherosclerotic plaque components.
CONCLUSIONS
Chemoradiotherapy may induce damage to endothelial cells, resulting in an inflammatory response. Negative remodeling of blood vessels is likely to occur, primarily characterized by vasoconstriction but with less atherosclerotic plaque burden. Routine stent implantation in negatively remodeled areas may lead to vascular rupture, necessitating intravascular imaging examination.
Topics: Humans; Male; Thymus Neoplasms; Middle Aged; Treatment Outcome; Time Factors; Thymoma; Coronary Angiography; Vascular System Injuries; Coronary Vessels; Chemoradiotherapy
PubMed: 38778265
DOI: 10.1186/s12872-024-03948-2 -
Brazilian Journal of Medical and... 2024Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced...
Arthritis has important cardiovascular repercussions. Phenylephrine-induced vasoconstriction is impaired in rat aortas in the early phase of the adjuvant-induced arthritis (AIA), around the 15th day post-induction. Therefore, the present study aimed to verify the effects of AIA on hyporesponsiveness to phenylephrine in rat aortas. AIA was induced by intradermal injection of Mycobacterium tuberculosis (3.8 mg/dL) in the right hind paw of male Wistar rats (n=27). Functional experiments in isolated aortas were carried out 15 days after AIA induction. Morphometric and stereological analyses of the aortas were also performed 36 days after the induction of AIA. AIA did not promote structural modifications in the aortas at any of the time points studied. AIA reduced phenylephrine-induced contraction in endothelium-intact aortas, but not in endothelium-denuded aortas. However, AIA did not change KCl-induced contraction in either endothelium-intact or denuded aortas. L-NAME (non-selective NOS inhibitor), 1400W (selective iNOS inhibitor), and ODQ (guanylyl cyclase inhibitor) reversed AIA-induced hyporesponsiveness to phenylephrine in intact aortas. 7-NI (selective nNOS inhibitor) increased the contraction induced by phenylephrine in aortas from AIA rats. In summary, the hyporesponsiveness to phenylephrine induced by AIA was endothelium-dependent and mediated by iNOS-derived NO through activation of the NO-guanylyl cyclase pathway.
Topics: Animals; Male; Phenylephrine; Rats, Wistar; Arthritis, Experimental; Nitric Oxide; Vasoconstriction; Endothelium, Vascular; Vasoconstrictor Agents; Rats; Aorta
PubMed: 38775546
DOI: 10.1590/1414-431X2024e13304 -
Journal of Veterinary Internal Medicine May 2024Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and...
BACKGROUND
Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH.
HYPOTHESIS
Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet-leukocyte, and platelet-neutrophil aggregate formation.
ANIMALS
Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH.
METHODS
Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3-view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet-leukocyte/platelet-neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA.
RESULTS
Unstimulated platelets from dogs with MMVD and PH expressed more surface P-selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet-leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet-neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups.
CONCLUSION AND CLINICAL IMPORTANCE
Platelet hyperresponsiveness and increased platelet-neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.
PubMed: 38773707
DOI: 10.1111/jvim.17067 -
Acta Pharmacologica Sinica May 2024The endothelium, lining the inner surface of blood vessels and spanning approximately 3 m, serves as the largest organ in the body. Comprised of endothelial cells, the...
The endothelium, lining the inner surface of blood vessels and spanning approximately 3 m, serves as the largest organ in the body. Comprised of endothelial cells, the endothelium interacts with other bodily components including the bloodstream, circulating cells, and the lymphatic system. Functionally, the endothelium primarily synchronizes vascular tone (by balancing vasodilation and vasoconstriction) and prevents vascular inflammation and pathologies. Consequently, endothelial dysfunction disrupts vascular homeostasis, leading to vascular injuries and diseases such as cardiovascular, cerebral, and metabolic diseases. In this opinion/perspective piece, we explore the recently identified mechanisms of endothelial dysfunction across various disease subsets and critically evaluate the strengths and limitations of current therapeutic interventions at the pre-clinical level.
PubMed: 38773228
DOI: 10.1038/s41401-024-01295-8 -
European Journal of Internal Medicine May 2024
PubMed: 38772829
DOI: 10.1016/j.ejim.2024.05.021 -
Archivos Argentinos de Pediatria May 2024Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations...
Raynaud's phenomenon consists of excessive contraction of the blood vessels in response to various stimuli; although it usually affects the extremities, other locations are less frequently involved. This study focused on describing the characteristics of a series of women with Raynaud's phenomenon of the nipple. Through medical record review and direct communication with patients, data from 12 women diagnosed with Raynaud's phenomenon of the nipple between 2016 and 2023 were collected and analyzed. The following variables were assessed: age, symptoms, triggering factors, treatment, and duration of symptoms. In this case series, Raynaud's phenomenon of the nipple in breastfeeding women was more common among primiparous women around 10 days after delivery; pain was severe and, in most cases, improved with local and/or drug treatment, and did not limit the duration of breastfeeding.
PubMed: 38771559
DOI: 10.5546/aap.2023-10280.eng -
Revista Brasileira de Ginecologia E... 2024Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium...
OBJECTIVE
Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies.
METHODS
To investigate the effects of the inhibition of K, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin.
RESULTS
There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights.
CONCLUSION
In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Umbilical Arteries; Adult; Glyburide; Vasoconstriction; Young Adult; KATP Channels; Potassium Chloride
PubMed: 38765503
DOI: 10.61622/rbgo/2024AO02