-
Frontiers in Medicine 2024Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase...
BACKGROUND
Methylene blue is an interesting approach in reducing fluid overload and vasoactive drug administration in vasodilatory shock. The inhibition of guanylate cyclase induced by methylene blue infusion reduces nitric oxide production and improves vasoconstriction. This systematic review and meta-analysis aimed to assess the effects of methylene blue administration compared to placebo on the hemodynamic status and clinical outcomes in patients with sepsis and septic shock.
METHODS
The authors specifically included randomized controlled trials that compared the use of methylene blue with placebo in adult patients with sepsis and septic shock. The outcomes were length of intensive care unit stay, hemodynamic parameters [vasopressor use], and days on mechanical ventilation. We also evaluated the abnormal levels of methemoglobinemia. This systematic review and meta-analysis were recorded in PROSPERO with the ID CRD42023423470.
RESULTS
During the initial search, a total of 1,014 records were identified, out of which 393 were duplicates. Fourteen citations were selected for detailed reading, and three were selected for inclusion. The studies enrolled 141 patients, with 70 of them in the methylene blue group and 71 of them in the control group. Methylene blue treatment was associated with a lower length of intensive care unit stay (MD -1.58; 95%CI -2.97, -0.20; = 25%; = 0.03), decreased days on mechanical ventilation (MD -0.72; 95%CI -1.26, -0.17; = 0%; = 0.010), and a shorter time to vasopressor discontinuation (MD -31.49; 95%CI -46.02, -16.96; = 0%; < 0.0001). No association was found with methemoglobinemia.
CONCLUSION
Administering methylene blue to patients with sepsis and septic shock leads to reduced time to vasopressor discontinuation, length of intensive care unit stay, and days on mechanical ventilation.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023423470, CRD42023423470.
PubMed: 38698779
DOI: 10.3389/fmed.2024.1366062 -
Arquivos Brasileiros de Cardiologia Apr 2024Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role...
BACKGROUND
Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling.
OBJECTIVE
Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms.
METHODS
Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%.
RESULTS
T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates.
CONCLUSION
T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.
Topics: Animals; Vasodilation; Male; Triiodothyronine; Rats, Wistar; Oxidation-Reduction; Reactive Oxygen Species; Oxidative Stress; Phenylephrine; Endothelium, Vascular; Rats; Reproducibility of Results; Vasoconstrictor Agents; Aorta, Thoracic; In Vitro Techniques; Vasoconstriction
PubMed: 38695407
DOI: 10.36660/abc.20230236 -
Heliyon May 2024Sternal 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...
BACKGROUND
Sternal 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).
METHODS
We 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.
RESULTS
A 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).
CONCLUSION
The 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.
PubMed: 38694077
DOI: 10.1016/j.heliyon.2024.e29991 -
Frontiers in Neuroscience 2024Migraine is one of the world's most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These... (Review)
Review
Migraine is one of the world's most debilitating disorders, and it has recently been shown that changes in the retina can be a potential biomarker for the disease. These changes can be detected by optical coherence tomography (OCT), which measures retinal thickness, and optical coherence tomography angiography (OCTA), which measures vessel density. We searched the databases Google Scholar, ProQuest, Scopus, and Web of Science for studies in English using OCT and OCTA in migraineurs, using the search terms "optical coherence tomography," "OCT," "optical coherence tomography angiography," "OCTA" and "migraine." We found 73 primary studies, 11 reviews, and 8 meta-analyses pertaining to OCT and OCTA findings in migraineurs. They showed that migraineurs had reduced retinal thickness (via OCT), retinal vessel density, and greater foveal avascular zone area (via OCTA) than controls. OCTA changes reflect a perfusion compromise occurring in migraineurs as opposed to in healthy controls. OCT and OCTA deficits were worse in migraine-with-aura and chronic migraine than in migraine-without-aura and episodic migraine. Certain areas of the eye, such as the fovea, may be more vulnerable to these perfusion changes than other parts. Direct comparison between study findings is difficult because of the heterogeneity between the studies in terms of both methodology and analysis. Moreover, as almost all case-control studies were cross-sectional, more longitudinal cohort studies are needed to determine cause and effect between migraine pathophysiology and OCT/OCTA findings. Current evidence suggests both OCT and OCTA may serve as retinal markers for migraineurs, and further research in this field will hopefully enable us to better understand the vascular changes associated with migraine, perhaps also providing a new diagnostic and therapeutic biomarker.
PubMed: 38686331
DOI: 10.3389/fnins.2024.1376282 -
Cureus Mar 2024This report describes the case of an 18-year-old Micronesian pregnant woman at 32 weeks gestation, initially presumed to have eclampsia but later diagnosed with...
This report describes the case of an 18-year-old Micronesian pregnant woman at 32 weeks gestation, initially presumed to have eclampsia but later diagnosed with reversible cerebral vasoconstriction syndrome (RCVS). She presented with seizures, altered mental status, nystagmus, lower extremity weakness, and absent reflexes. An extensive workup ruled out infectious and autoimmune causes, but a computed tomography angiogram (CTA) revealed severe cerebral vasoconstriction. Treatment included levetiracetam, intravenous magnesium, and nimodipine. The case highlights the challenge of differentiating RCVS from eclampsia in the postpartum period, emphasizing the importance of considering alternative diagnoses and brain CTA when RCVS is suspected, with calcium channel blockers potentially contributing to favorable neurological outcomes.
PubMed: 38681466
DOI: 10.7759/cureus.57021 -
Pharmaceuticals (Basel, Switzerland) Mar 2024Exposure to hypoxia results in the development of pulmonary arterial hypertension (PAH). An increase in the intracellular Ca concentration ([Ca]) in pulmonary artery...
Exposure to hypoxia results in the development of pulmonary arterial hypertension (PAH). An increase in the intracellular Ca concentration ([Ca]) in pulmonary artery smooth muscle cells (PASMCs) is a major trigger for pulmonary vasoconstriction and proliferation. This study investigated the mechanism by which KMUP-1, a xanthine derivative with phosphodiesterase inhibitory activity, inhibits hypoxia-induced canonical transient receptor potential channel 1 (TRPC1) protein overexpression and regulates [Ca] through store-operated calcium channels (SOCs). Ex vivo PASMCs were cultured from Sprague-Dawley rats in a modular incubator chamber under 1% O/5% CO for 24 h to elucidate TRPC1 overexpression and observe the Ca release and entry. KMUP-1 (1 μM) inhibited hypoxia-induced TRPC family protein encoded for SOC overexpression, particularly TRPC1. KMUP-1 inhibition of TRPC1 protein was restored by the protein kinase G (PKG) inhibitor KT5823 (1 μM) and the protein kinase A (PKA) inhibitor KT5720 (1 μM). KMUP-1 attenuated protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA, 1 μM)-upregulated TRPC1. We suggest that the effects of KMUP-1 on TRPC1 might involve activating the cyclic guanosine monophosphate (cGMP)/PKG and cyclic adenosine monophosphate (cAMP)/PKA pathways and inhibiting the PKC pathway. We also used Fura 2-acetoxymethyl ester (Fura 2-AM, 5 μM) to measure the stored calcium release from the sarcoplasmic reticulum (SR) and calcium entry through SOCs in hypoxic PASMCs under treatment with thapsigargin (1 μM) and nifedipine (5 μM). In hypoxic conditions, store-operated calcium entry (SOCE) activity was enhanced in PASMCs, and KMUP-1 diminished this activity. In conclusion, KMUP-1 inhibited the expression of TRPC1 protein and the activity of SOC-mediated Ca entry upon SR Ca depletion in hypoxic PASMCs.
PubMed: 38675401
DOI: 10.3390/ph17040440 -
Nutrients Apr 2024Copper (Cu), being an essential mineral, plays a crucial role in maintaining physiological homeostasis across multiple bodily systems, notably the cardiovascular system....
Copper (Cu), being an essential mineral, plays a crucial role in maintaining physiological homeostasis across multiple bodily systems, notably the cardiovascular system. However, an increased Cu level in the body may cause blood vessel dysfunction and oxidative stress, which is unfavorable for the cardiovascular system. Middle-aged (7-8 months old) male Wistar rats (n/group = 12) received a diet supplemented with 6.45 mg Cu/kg (100% of the recommended daily dietary quantity of copper) for 8 weeks (Group A). The experimental group received 12.9 mg Cu/kg of diet (200%-Group B). An ex vivo study revealed that supplementation with 200% Cu decreased the contraction of isolated aortic rings to noradrenaline (0.7-fold) through FP receptor modulation. Vasodilation to sodium nitroprusside (1.10-fold) and acetylcholine (1.13-fold) was potentiated due to the increased net effect of prostacyclin derived from cyclooxygenase-1. Nitric oxide (NO, 2.08-fold), superoxide anion (O, 1.5-fold), and hydrogen peroxide (HO, 2.33-fold) measured in the aortic rings increased. Blood serum antioxidant status (TAS, 1.6-fold), Cu (1.2-fold), Zn (1.1-fold), and the Cu/Zn ratio (1.4-fold) increased. An increase in Cu (1.12-fold) and the Cu/Zn ratio (1.09-fold) was also seen in the rats' livers. Meanwhile, cyclooxygenase-1 (0.7-fold), cyclooxygenase-2 (0.4-fold) and glyceraldehyde 3-phosphate dehydrogenase (0.5-fold) decreased. Moreover, a negative correlation between Cu and Zn was found (r = -0.80) in rat serum. Supplementation with 200% Cu did not modify the isolated heart functioning. No significant difference was found in the body weight, fat/lean body ratio, and organ weight for either the heart or liver, spleen, kidney, and brain. Neither Fe nor Se, the Cu/Se ratio, the Se/Zn ratio (in serum and liver), heme oxygenase-1 (HO-1), endothelial nitric oxide synthase (eNOS), or intercellular adhesion molecule-1 (iCAM-1) (in serum) were modified. Supplementation with 200% of Cu potentiated pro-oxidant status and modified vascular contractility in middle-aged rats.
Topics: Animals; Male; Copper; Rats, Wistar; Oxidative Stress; Rats; Vasoconstriction; Antioxidants; Vasodilation; Dietary Supplements; Aorta
PubMed: 38674863
DOI: 10.3390/nu16081172 -
International Journal of Molecular... Apr 2024Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper"...
Using a lipopolysaccharide model of acute lung injury, we previously showed that endothelin-1 (ET-1), a potent mediator of vasoconstriction, may act as a "gatekeeper" for the influx of inflammatory cells into the lung. These studies provided a rationale for testing the effect of HJP272, an endothelin receptor antagonist (ERA), in hamster models of pulmonary fibrosis induced by intratracheal instillation of either bleomycin (BLM) or amiodarone (AM). To determine the temporal effects of blocking ET-1 activity, animals were given HJP272 either 1 h before initiation of lung injury or 24 h afterward. The results indicated that pretreatment with this agent caused significant reductions in various inflammatory parameters, whereas post-treatment was ineffective. This finding suggests that ERAs are only effective at a very early stage of pulmonary fibrosis and explains their lack of success in clinical trials involving patients with this disease. Nevertheless, ERAs could serve as prophylactic agents when combined with drugs that may induce pulmonary fibrosis. Furthermore, developing a biomarker for the initial changes in the lung extracellular matrix could increase the efficacy of ERAs and other therapeutic agents in preventing the progression of the disease. While no such biomarker currently exists, we propose the ratio of free to peptide-bound desmosine, a unique crosslink of elastin, as a potential candidate for detecting the earliest modifications in lung microarchitecture associated with pulmonary fibrosis.
Topics: Animals; Pulmonary Fibrosis; Endothelin Receptor Antagonists; Bleomycin; Cricetinae; Disease Models, Animal; Male; Lung; Humans; Endothelin-1
PubMed: 38673771
DOI: 10.3390/ijms25084184 -
Journal of Clinical Medicine Apr 2024: Owing to the association between dysfunctional maternal autonomic regulation and pregnancy complications, assessing non-invasive features reflecting autonomic...
: Owing to the association between dysfunctional maternal autonomic regulation and pregnancy complications, assessing non-invasive features reflecting autonomic activity-e.g., heart rate variability (HRV) and the morphology of the photoplethysmography (PPG) pulse wave-may aid in tracking maternal health. However, women with early pregnancy complications typically receive medication, such as corticosteroids, and the effect of corticosteroids on maternal HRV and PPG pulse wave morphology is not well-researched. : We performed a prospective, observational study assessing the effect of betamethasone (a commonly used corticosteroid) on non-invasively assessed features of autonomic regulation. Sixty-one women with an indication for betamethasone were enrolled and wore a wrist-worn PPG device for at least four days, from which five-minute measurements were selected for analysis. A baseline measurement was selected either before betamethasone administration or sufficiently thereafter (i.e., three days after the last injection). Furthermore, measurements were selected 24, 48, and 72 h after betamethasone administration. HRV features in the time domain and frequency domain and describing heart rate (HR) complexity were calculated, along with PPG morphology features. These features were compared between the different days. : Maternal HR was significantly higher and HRV features linked to parasympathetic activity were significantly lower 24 h after betamethasone administration. Features linked to sympathetic activity remained stable. Furthermore, based on the PPG morphology features, betamethasone appears to have a vasoconstrictive effect. : Our results suggest that administering betamethasone affects maternal autonomic regulation and cardiovasculature. Researchers assessing maternal HRV in complicated pregnancies should schedule measurements before or sufficiently after corticosteroid administration.
PubMed: 38673715
DOI: 10.3390/jcm13082442 -
Children (Basel, Switzerland) Mar 2024The effect of pediatric inguinal hernia repair (IHR) on testicular vascularization remains unclear. Manipulating the spermatic cord during surgery may reduce blood flow... (Review)
Review
BACKGROUND
The effect of pediatric inguinal hernia repair (IHR) on testicular vascularization remains unclear. Manipulating the spermatic cord during surgery may reduce blood flow due to edema and vasoconstriction. This can lead to testicular atrophy. The study aims to review current knowledge of testicular vascular impairment following IHR in children.
METHODS
A systematic literature search was conducted in PubMed/Medline, Embase, Cochrane Library, and Web of Science. Methodological quality was assessed using validated tools. Data were extracted, and a pooled data analysis was performed.
RESULTS
Ten studies were included in the systematic review. Six of these studies were eligible for meta-analysis. This revealed a significant decrease in testicular vascularization during the short-term follow-up (1 day-1 week) after IHR using the open surgical approach. This decrease was not present after laparoscopic intervention. There was no more increased resistance in the vessels at long-term follow-up (1 month-6 months), suggesting that the impaired vascularity is only temporary.
CONCLUSIONS
There seems to be a short-term transient vascular impairment of the testis after open IHR in children. This might be of clinical relevance to prefer the laparoscopic approach for IHR in children, even though the open approach is the gold standard, in contrast to adult IHR. The impact on testicular function and sperm quality later in life remains unclear. Comparative studies of both techniques are needed to determine if there is a significant difference in testicular vascularity. Long-term studies are necessary to assess the impact of transiently reduced vascularity on sperm quality and fertility later in life.
PubMed: 38671625
DOI: 10.3390/children11040409