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Cell Biochemistry and Biophysics Jun 2024Rho-kinase (ROCK) regulates actomyosin contraction, coronary vasospasm, and cytoskeleton dynamics. ROCK and of NADPH oxidase (NOX) play an essential role in...
BACKGROUND
Rho-kinase (ROCK) regulates actomyosin contraction, coronary vasospasm, and cytoskeleton dynamics. ROCK and of NADPH oxidase (NOX) play an essential role in cardiovascular disease and proteoglycan synthesis, which promotes atherosclerosis by trapping low density lipoprotein. ROCK is activated by endothelin-1 (ET1) and transactivates the transforming growth factor beta receptor (TGFβR1), intensifying Smad signaling and proteoglycan production. This study aimed to identify the role of myosin light chain phosphatase (MLCP) as a downstream target of ROCK in TβR1 transactivation.
METHODS
Vascular smooth muscle cells were treated with ET1 and inhibitors of ROCK and MLCP were added. The phosphorylation levels of Smad2C, myosin light chain (MLC), and MLCP were monitored by western blot, and the mRNA expression of chondroitin 4-O-sulfotransferase 1 (C4ST1) was assessed by quantitative real-time PCR.
RESULTS
We examined ROCK's role in ET1-induced TGFβR1 activation. ROCK phosphorylated MLCP at the MYPT1 T853 residue, blocked by the ROCK inhibitor Y27632. ROCK also increased MLC phosphorylation and actomyosin contraction in response to ET1, enhanced by the phosphatase inhibitor Calyculin A. Calyculin A also increased C4ST1 expression, GAG-chain synthesizing enzymes.
CONCLUSIONS
This work suggests that ROCK is involved in ET1-mediated TβR1 activation through increased MLCP phosphorylation, which leads to Smad2C phosphorylation and stimulates C4ST1 expression.
PubMed: 38834831
DOI: 10.1007/s12013-024-01262-4 -
Acta Neurochirurgica Jun 2024Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling.
BACKGROUND
Thyroid hormones were reported to exert neuroprotective effects after ischemic stroke by reducing the burden of brain injury and promoting post-ischemic brain remodeling.
OBJECTIVE
We aimed to analyze the value of thyroid hormone replacement therapy (THRT) due to pre-existing hypothyroidism on the clinical course and outcome of aneurysmal subarachnoid hemorrhage (SAH).
METHODS
SAH individuals treated between January 2003 and June 2016 were included. Data on baseline characteristics of patients and SAH, adverse events and functional outcome of SAH were recorded. Study endpoints were cerebral infarction, in-hospital mortality and unfavorable outcome at 6 months. Associations were adjusted for outcome-relevant confounders.
RESULTS
109 (11%) of 995 individuals had THRT before SAH. Risk of intracranial pressure- or vasospasm-related cerebrovascular events was inversely associated with presence of THRT (p = 0.047). In multivariate analysis, THRT was independently associated with lower risk of cerebral infarction (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] = 0.41-0.99, p = 0.045) and unfavorable outcome (aOR = 0.50, 95% CI = 0.28-0.89, p = 0.018), but not with in-hospital mortality (aOR = 0.69, 95% CI = 0.38-1.26, p = 0.227).
CONCLUSION
SAH patients with THRT show lower burden of ischemia-relevant cerebrovascular events and more favorable outcome. Further experimental and clinical studies are required to confirm our results and elaborate the mechanistic background of the effect of THRT on course and outcome of SAH.
Topics: Humans; Subarachnoid Hemorrhage; Female; Male; Middle Aged; Hormone Replacement Therapy; Aged; Thyroid Hormones; Treatment Outcome; Hospital Mortality; Adult; Hypothyroidism; Retrospective Studies; Cerebral Infarction; Vasospasm, Intracranial
PubMed: 38829543
DOI: 10.1007/s00701-024-06118-7 -
Radiology Case Reports Aug 2024We report a case of acute myocardial infarction in a patient with polycythemia rubra vera, who has been treated with hydroxyurea. The patient presented with chest pain...
We report a case of acute myocardial infarction in a patient with polycythemia rubra vera, who has been treated with hydroxyurea. The patient presented with chest pain extending to both arms accompanied by nausea and sweating. Hemoglobin was 18.1 mg/dL, hematocrit 53.2%, white blood cells 9600/mm³, and platelets 745,000/mm³. The levels of specific cardiac injury markers were increased, troponin I increased to 110 ng/mL and creatine kinase-MB to 361 U/l, respectively. Electrocardiography showed sinus rhythm with ST-segment elevation in leads V2-6, D1, and aVL as well as ST depression in D2, D3 and aVF. Echocardiography demonstrated hypokinesis of the interventricular septum and lateral wall with mildly reduced left ventricle (LV) ejection fraction (EF≈45%). Coronary angiography revealed proximal-LAD subtotal occlusion and 80% mid-LAD stenosis with distal-LAD vasospasm. Percutaneous coronary intervention was performed with a drug-eluting stent in mid- and proximal-LAD. Hypercoagulable state of polycythemia rubra vera may be complicated with acute myocardial infarction, in addition to the vasospastic effect and endothelium lesions of hydroxyurea regardless its favorable effect as a standard therapy.
PubMed: 38827039
DOI: 10.1016/j.radcr.2024.05.014 -
Journal of Electrocardiology May 2024A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelve‑lead ECG on admission exhibited prominent J waves...
A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelve‑lead ECG on admission exhibited prominent J waves in the inferolateral leads. During the treatment for hyponatremia, ventricular fibrillation (VF) occurred and the electrogram (ECG) after the VF incident exhibited marked ST elevation in the inferolateral leads. An Ach provocation test induced vasospasms in the right and left coronary arteries and J wave augmentation, suggesting a high risk for vasospastic angina. Finally, a subcutaneous implantable cardioverter defibrillator was implanted in the patient. We hereby discuss the possible contribution of hyponatremia to VF episodes in early repolarization syndrome based on the present case.
PubMed: 38823212
DOI: 10.1016/j.jelectrocard.2024.05.098 -
Child's Nervous System : ChNS :... May 2024Teratomas account for 18-20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar...
Teratomas account for 18-20% of all intracranial germ cell tumors and mostly occur in the pineal region with only a few cases of pediatric sellar and suprasellar teratomas described in the literature. Here, we present a case of a child with an intracranial mature teratoma with pancreatic features causing vasospasm and subsequent stroke, found to be positive for CDKN2A-an independent variant associated with malignancy and small vessel disease leading to stroke.
PubMed: 38819669
DOI: 10.1007/s00381-024-06471-z -
Clinical Neuroradiology May 2024The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate the...
PURPOSE
The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate the effect of adding nimodipine to the guiding catheter flush (GCF) to prevent vasospasm during EVT.
METHODS
This is a single-center retrospective analysis including patients with EVT (stent-retriever and/or distal aspiration) treated for anterior or posterior circulation intracranial vessel occlusion from January 2018 to June 2023. Exclusion criteria were intracranial or extracranial stenosis, intra-arterial alteplase, patient age over 80 years. Study groups were patients with (nimo+) and without (nimo-) nimodipine in the GCF. They were compared for occurrence of vasospasm as primary endpoint and clinical outcome in univariate analysis.
RESULTS
477 patients were included in the analysis (nimo+ n = 94 vs. nimo- n = 383). Nimo+ patients experienced less vasospasm during EVT (e.g. vasospasm in target vessel n (%): nimo- = 113 (29.6) vs. nimo+ = 9 (9.6), p < 0.001; extracranial vasospasm, n (%): nimo- = 68 (17.8) vs. nimo+ = 7 (7.4), p = 0.017). Patients of the two study groups had a comparable clinical outcome (90 day mRS, median (IQR): 3 (1-6) for both groups, p = 0.896). In general, patients with anterior circulation target vessel occlusion (TVO) experienced more vasospasm (anterior circ. TVO 38.7% vs. posterior circ. 7.5%, p = 0.006).
CONCLUSION
Prophylactic adding of nimodipine reduces the risk of vasospasm during EVT without affecting the clinical outcome. Patients with anterior circulation TVO experienced more vasospasm compared to posterior circulation TVO.
PubMed: 38819643
DOI: 10.1007/s00062-024-01424-0 -
European Heart Journal. Case Reports May 2024Vasospastic angina (VSA) is uncommon in premenopausal women who have less chronic endothelial injury causing vascular remodelling, considered to play a primary role in...
BACKGROUND
Vasospastic angina (VSA) is uncommon in premenopausal women who have less chronic endothelial injury causing vascular remodelling, considered to play a primary role in the pathogenesis for coronary vasospasms. Furthermore, vasospasms rarely occur in the bilateral coronary ostia. Isolated coronary ostial stenosis (ICOS), which often causes severe effort angina and requires surgical intervention, is more commonly reported in middle-aged women, with causes including fibromuscular dysplasia (FMD) and large-vessel vasculitis. However, ICOS associated with VSA is extremely rare.
CASE SUMMARY
A 50-year-old premenopausal Japanese woman presented with a complaint of typical chest pain due to angina during light exertion daily in the early morning hours since 3 years. Coronary angiography (CAG) revealed bilateral mild-to-moderate ICOS in addition to multi-vessel spasms involving the bilateral coronary ostia confirmed by the vasospasm provocation test using intracoronary acetylcholine injection. Tests to determine the cause of ICOS did not identify FMD or any other disease. The angina attacks alleviated after calcium channel blocker (CCB) administration without intervention for bilateral ICOS for 24 years since the first presentation. Moreover, coronary computed tomography angiography (CTA) performed 24 years after the first presentation showed no ICOS.
DISCUSSION
In our patient with typical and frequent VSA symptoms, CAG revealed both mild-to-moderate ICOS and the vasospasms in the bilateral coronary ostia. Fibromuscular dysplasia or large-vessel vasculitis was ruled out as the causes of ICOS. Vasospastic angina rarely occurred after the prescription of CCB, and coronary CTA 24 years after the first presentation showed no ICOS. Bilateral ICOS in our patient might be VSA related.
PubMed: 38817315
DOI: 10.1093/ehjcr/ytae249 -
AJNR. American Journal of Neuroradiology May 2024Delayed cerebral ischemia and vasospasm are the most common causes of late morbidity following aneurysmal SAH, but their diagnosis remains challenging.
BACKGROUND
Delayed cerebral ischemia and vasospasm are the most common causes of late morbidity following aneurysmal SAH, but their diagnosis remains challenging.
PURPOSE
This systematic review and meta-analysis investigated the diagnostic performance of CTP for detection of delayed cerebral ischemia and vasospasm in the setting of aneurysmal SAH.
DATA SOURCES
Studies evaluating the diagnostic performance of CTP in the setting of aneurysmal SAH were searched on the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Clinical Answers, Cochrane Methodology Register, Ovid MEDLINE, EMBASE, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Health Technology Assessment, National Health Service Economic Evaluation Database, PubMed, and Google Scholar from their inception to September 2023.
STUDY SELECTION
Thirty studies were included, encompassing 1786 patients with aneurysmal SAH and 2302 CTP studies. Studies were included if they compared the diagnostic accuracy of CTP with a reference standard (clinical or radiologic delayed cerebral ischemia, angiographic spasm) for the detection of delayed cerebral ischemia or vasospasm in patients with aneurysmal SAH. The primary outcome was accuracy for the detection of delayed cerebral ischemia or vasospasm.
DATA ANALYSIS
Bivariate random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Subgroup analyses for individual CTP parameters and early-versus-late study timing were performed. Bias and applicability were assessed using the modified QUADAS-2 tool.
DATA SYNTHESIS
For assessment of delayed cerebral ischemia, CTP demonstrated a pooled sensitivity of 82.1% (95% CI, 74.5%-87.8%), specificity of 79.6% (95% CI, 73.0%-84.9%), positive likelihood ratio of 4.01 (95% CI, 2.94-5.47), and negative likelihood ratio of 0.23 (95% CI, 0.12-0.33). For assessment of vasospasm, CTP showed a pooled sensitivity of 85.6% (95% CI, 74.2%-92.5%), specificity of 87.9% (95% CI, 79.2%-93.3%), positive likelihood ratio of 7.10 (95% CI, 3.87-13.04), and negative likelihood ratio of 0.16 (95% CI, 0.09-0.31).
LIMITATIONS
QUADAS-2 assessment identified 12 articles with low risk, 11 with moderate risk, and 7 with a high risk of bias.
CONCLUSIONS
For delayed cerebral ischemia, CTP had a sensitivity of >80%, specificity of >75%, and a low negative likelihood ratio of 0.23. CTP had better performance for the detection of vasospasm, with sensitivity and specificity of >85% and a low negative likelihood ratio of 0.16. Although the accuracy offers the potential for CTP to be used in limited clinical contexts, standardization of CTP techniques and high-quality randomized trials evaluating its impact are required.
PubMed: 38816018
DOI: 10.3174/ajnr.A8249 -
Therapeutic Hypothermia and Temperature... May 2024The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the... (Review)
Review
The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk (RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.
PubMed: 38813648
DOI: 10.1089/ther.2024.0001 -
Transplantation Jun 2024
Topics: Humans; Heart Transplantation; Coronary Vasospasm; Heart Arrest; Recurrence; Male; Middle Aged; Treatment Outcome; Coronary Angiography; Female
PubMed: 38809433
DOI: 10.1097/TP.0000000000004975