scholarly journals Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis

2020 ◽  
Vol 40 (8) ◽  
pp. 1565-1575 ◽  
Author(s):  
Julian V Clarke ◽  
Julia M Suggs ◽  
Deepti Diwan ◽  
Jin V Lee ◽  
Kim Lipsey ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Subarachnoid Hemorrhage ◽  
Platelet Aggregation ◽  
Randomized Clinical Trials ◽  
Experimental Studies ◽  
Delayed Cerebral Ischemia ◽  
Therapeutic Options ◽  
Large Artery ◽  
Ongoing Research ◽  
Human Autopsy

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been associated with numerous pathophysiological sequelae, including large artery vasospasm and microvascular thrombosis. The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal-spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following SAH, as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process. Upon review of the literature, we discovered that microvascular platelet aggregation and thrombosis occur after experimental SAH across multiple species and SAH induction techniques in a similar time frame to other components of DCI, occurring in the cerebral cortex and hippocampus across both hemispheres. We discuss the relationship of these findings to human autopsy studies. In the final section of this review, we highlight the important therapeutic options for targeting microvascular platelet aggregation and thrombosis, and emphasize why therapeutic targeting of this neurovascular pathology may improve patient care. We encourage ongoing research into the pathophysiology of SAH and DCI, especially in regard to microvascular platelet aggregation and thrombosis and the translation to randomized clinical trials.

scholarly journals Sevoflurane and Desflurane Exposures Following Aneurysmal Subarachnoid Hemorrhage Confer Multifaceted Protection against Delayed Cerebral Ischemia

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 820
Author(s):  
Keshav Jayaraman ◽  
Meizi Liu ◽  
Gregory J. Zipfel ◽  
Umeshkumar Athiraman
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Preclinical Studies ◽  
Large Artery ◽  
Sham Surgery ◽  
Neurological Patients ◽  
Neurologic Function ◽  
Preclinical And Clinical Studies

Numerous studies have demonstrated the ability of isoflurane conditioning to provide multifaceted protection against aneurysmal subarachnoid hemorrhage (SAH)-associated delayed cerebral ischemia (DCI); however, preclinical studies have not yet examined whether other commonly used inhalational anesthetics in neurological patients such as sevoflurane or desflurane are also protective against SAH-induced neurovascular deficits. We therefore sought to identify the potential for sevoflurane and desflurane conditioning to protect against DCI in an endovascular perforation mouse model of SAH. Neurological function was assessed daily via neuroscore. Large artery vasospasm and microvessel thrombosis were assessed three days after SAH or sham surgery. Four groups were examined: Sham, SAH + room air, SAH + 2% Sevoflurane, and SAH + 6% Desflurane. For the SAH groups, one hour after surgery, mice received 2% sevoflurane, 6% desflurane, or room air for one hour. We found that conditioning with sevoflurane or desflurane attenuated large artery vasospasm, reduced microvessel thrombosis, and improved neurologic function. Given their frequent clinical use and strong safety profile in patients (including those with SAH), these data strongly support further studies to validate these findings in preclinical and clinical studies and to elucidate the mechanisms by which these agents might be acting.

scholarly journals Clinical Outcomes of Aspirin Interaction with Other Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review

2018 ◽  
Vol 21 (1s) ◽  
pp. 48s-73s ◽  
Author(s):  
Zuhair Alqahtani ◽  
Fakhreddin Jamali
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Clinical Outcomes ◽  
Randomized Clinical Trials ◽  
Ex Vivo ◽  
Biologically Active ◽  
Cardioprotective Effect ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Aggregation Level

Purpose: Concomitant use of some non-Aspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) reduces the extent of platelet aggregation of Aspirin (acetylsalicylic acid). This is while many observational studies and clinical trials suggest that Aspirin reduces cardiovascular (CV) risk attributed to the use of NANSAIDs. Thus, the therapeutic outcome of the interaction needs to be assessed. Methods: We searched various databases up to October 2017 for molecular interaction studies between the drugs and long-term clinical outcomes based on randomized clinical trials and epidemiological observations that reported the effect estimates of CV risks (OR, RR or HR; 95% CI) of the interacting drugs alone or in combinations. Comparisons were made between outcomes after Aspirin alone, NANSAIDs alone and Aspirin with naproxen, ibuprofen, celecoxib, meloxicam, diclofenac or rofecoxib. Results: In total, 32 eligible studies (20 molecular interactions studies and 12 observational trials) were found. Conflicting in vitro/in vivo/ex vivo platelet aggregation data were found for ibuprofen, naproxen and celecoxib. Nevertheless, for naproxen, the interaction at the aggregation level did not amount to a loss of cardioprotective effects of Aspirin. Similarly, for ibuprofen, the results overwhelmingly suggest no negative clinical CV outcomes following the combination therapy. Meloxicam and rofecoxib neither interacted with Aspirin at the level of platelet aggregation nor altered clinical outcomes. The clinical outcomes data for celecoxib and diclofenac are in conflict. Conclusion: Aspirin appears to maintain its cardioprotective effect in the presence of naproxen, ibuprofen, meloxicam and rofecoxib. The limited available data suggest that the effect of interaction at the platelet aggregation level may dissipate shortly, or the reduced platelet aggregation yielded by the interaction may be sufficient for cardioprotection; i.e., no need for near complete aggregation. In addition, cardioprotective effect of Aspirin, despite reduced platelet aggregation caused by NANSAIDs, may be through its involvement in other mechanisms such as the renin-angiotensin system and/or metabolism of arachidonic acid to biologically active compounds mediated by cytochrome P450. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Opening windows of opportunities: Evidence for interventions to prevent or treat depression in pregnant women being associated with changes in offspring's developmental trajectories of psychopathology risk

2018 ◽  
Vol 30 (3) ◽  
pp. 1179-1196 ◽  
Author(s):  
Sherryl H. Goodman ◽  
Katherine A. Cullum ◽  
Sona Dimidjian ◽  
Laura M. River ◽  
Christine Youngwon Kim
Keyword(s):  
Clinical Trials ◽  
Pregnant Women ◽  
Fetal Programming ◽  
Randomized Clinical Trials ◽  
Programming Model ◽  
Developmental Trajectories ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Behavioral Changes ◽  
Small Effect Size

AbstractAlthough animal models and correlational studies support a model of fetal programming as a mechanism in the transmission of risk for psychopathology from parents to children, the experimental studies that are required to empirically test the model with the human prenatal dyad are scarce. With a systematic review and meta-analysis of the literature, we critically examined the evidence regarding the neurobiological and behavioral changes in infants as a function of randomized clinical trials to prevent or reduce maternal depression during pregnancy, treating randomized clinical trials as experiments testing the fetal programming model. Based on 25 articles that met inclusion criteria, we found support for interventions designed to change maternal prenatal mood being associated with changes in offspring functioning, but with a very small effect size. Effect sizes ranged broadly, and were higher for younger children. The findings enhance understanding of putative mechanisms in the transmission of risk from women's prenatal depression to infants’ vulnerabilities to, and early signs of, the development of psychopathology. We note limitations of the literature and suggest solutions to advance understanding of how preventing or treating depression in pregnant women might disrupt the transmission of risk to the infants.

scholarly journals Análise da Revisão Cochrane: Terapêutica Farmacológica da Hiperuricemia em Doentes Hipertensos. Cochrane Database Syst Rev. 2017;4:CD008652.

2017 ◽  
Vol 30 (5) ◽  
pp. 356
Author(s):  
Miguel Bigotte Vieira ◽  
Rute Baeta Baptista ◽  
João Costa ◽  
António Vaz-Carneiro
Keyword(s):  
Blood Pressure ◽  
Clinical Trials ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Randomized Clinical Trials ◽  
Experimental Studies ◽  
Public Health Problem ◽  
Primary Hypertension ◽  
World Health ◽  
Cochrane Central Register

Arterial hypertension is a public health problem that affects approximately 25% of the world’s adult population. The association between hypertension and hyperuricemia has been shown on epidemiological and experimental studies. However, it is unclear whether lowering serum uric acid might lower blood pressure. This Cochrane systematic review - a revised edition of a previously published one - intended as primary objective to evaluate the effect of hypouricemic drugs in patients with primary hypertension or prehypertension. The secondary objectives were to evaluate the efficacy and safety of hypouricemic drugs. A systematic search until February 2016 on controlled, randomized or quasi-randomized trials comparing the effect of hypouricemic drug versus placebo in hypertensive or prehypertensive patients was performed on the following databases: The Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, The World Health Organization International Clinical Trials Registry Platform, e ClinicalTrials.gov. LILACS database up to March 2016 was also searched and the authors of relevant studies were contacted. There were 349 identified papers, 21 were preselected and three randomized clinical trials (211 patients) were included in the qualitative analysis and in the meta-analysis. Two of the trials were conducted exclusively on adolescents. The authors conclude that hypouricemic drugs are not effective in lowering blood pressure in patients with hyperuricemia and primary prehypertension or hypertension. However, this strategy might be more effective in the specific population of adolescents with prehypertension or mild primary hypertension recently diagnosed. Hypouricemic drugs effectively reduce serum uric acid level and withdrawals of therapy due to adverse effects were not superior in the treated group, comparing to placebo; however, one patient withdrew due to a severe cutaneous reaction.

Effectiveness of Biology-Based Methods for Inhibiting Orthodontic Tooth Movement. A Systematic Review

2017 ◽  
Vol 41 (6) ◽  
pp. 494-502 ◽  
Author(s):  
M Cadenas de Llano-Pérula ◽  
RM Yañez-Vico ◽  
E Solano-Reina ◽  
JC Palma-Fernandez ◽  
A Iglesias-Linares
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Continuous Wave ◽  
Tooth Movement ◽  
Experimental Studies ◽  
Orthodontic Tooth Movement ◽  
Low Level Laser Therapy ◽  
Cochrane Library ◽  
Level Laser

Introduction: Several experimental studies in the literature have tested different biology-based methods for inhibiting or decreasing orthodontic tooth movement (OTM) in humans. This systematic review investigated the effects of these interventions on the rate of tooth movement. Study design: Electronic [MedLine; SCOPUS; Cochrane Library; OpenGrey;Web of Science] and manual searches were conducted up to January 26th, 2016 in order to identify publications of clinical trials that compared the decreasing or inhibiting effects of different biology-based methods over OTM in humans. A primary outcome (rate of OTM deceleration/inhibition) and a number of secondary outcomes were examined (clinical applicability, orthodontic force used, possible side effects). Two reviewers selected the studies complying with the eligibility criteria (PICO format) and assessed risk of bias [Cochrane Collaboration's tool]. Data collection and analysis were performed following the Cochrane recommendations. Results: From the initial electronic search, 3726 articles were retrieved and 5 studies were finally included. Two types of biology-based techniques used to reduce the rate of OTM in humans were described: pharmacological and low-level laser therapy. In the first group, human Relaxin was compared to a placebo and administered orally. It was described as having no effect on the inhibition of OTM in humans after 32 days, while the drug tenoxicam, injected locally, inhibited the rate of OTM by up to 10% in humans after 42 days. In the second group, no statistically significant differences were reported, compared to placebo, for the rate of inhibition of OTM in humans after 90 days of observation when a 860 nm continuous wave GaAlA slow-level laser was used. Conclusions: The currently available data do not allow us to draw definitive conclusions about the use of various pharmacological substances and biology-based therapies in humans able to inhibit or decrease the OTM rate. There is an urgent need for more sound well-designed randomized clinical trials in the field.

scholarly journals Cardioprotective Properties Of Xenon

2020 ◽  
Vol 9 (2) ◽  
pp. 264-272
Author(s):  
A. I. Shpichko ◽  
O. A. Grebenchikov ◽  
I. V. Molchanov ◽  
A. K. Shabanov ◽  
N. P. Shpichko ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Randomized Clinical Trials ◽  
Protective Action ◽  
Experimental Studies ◽  
Molecular Targets ◽  
Cardiac Complications ◽  
Ischemia And Reperfusion

Abstract The review presents the main aspects of the cardioprotective properties of the xenon inhalation anesthetic. Based on the analysis of publications, the article discusses modern views on the mechanisms of the protective action of xenon, realized using pre- and post-conditioning mechanisms, shows major molecular targets and their effects. The article presents the results of experimental studies in vivo and in vitro, which showed the protective effect of xenon on the myocardium and the results of recent randomized clinical trials. The analysis of studies demonstrates the ability of xenon to increase myocardial resistance to ischemia and reperfusion and opens up good prospects for its use in clinical practice in patients with a high risk of cardiac complications.

scholarly journals New targets and old therapies for arterial hypertension

2019 ◽  
pp. 46-52
Author(s):  
S. R. Gilyarevsky ◽  
N. G. Bendeliani ◽  
M. V. Golshmid ◽  
G. Yu. Zakharova ◽  
I. M. Kuzmina ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Arterial Hypertension ◽  
Randomized Clinical Trials ◽  
Antihypertensive Drugs ◽  
Experimental Studies ◽  
The Elderly ◽  
Published Data ◽  
Efficacy And Safety ◽  
Adoption And Implementation ◽  
Moderate Cognitive Impairment

The article discusses approaches to the choice of antihypertensive drugs, which may be based on the adoption and implementation of new clinical guidelines for the management of patients with arterial hypertension. This paper provides data on the efficacy and safety of candesartan, an antihypertensive drug, which advantages were identified during a large number of randomized clinical trials. It discusses the recently published data on the effectiveness of more intensive regimens of antihypertensive therapy to reduce the risk of moderate cognitive impairment in patients with arterial hypertension. In this regard, the authors provide data of the previously completed studies, which showed the effect of candesartan on the rate of cognitive decline in patients with arterial hypertension in the elderly and senile age. The features of the pharmacological characteristics of candesaratan that can remotely explain its clinical efficacy are considered. The data of experimental studies of candesartan in animals, which contribute to the concept of the possible effects of candesartan, are presented.

scholarly journals Statins Improve Clinical Outcome After Non-aneurysmal Subarachnoid Hemorrhage: A Translational Insight From a Systematic Review of Experimental Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Sepide Kashefiolasl ◽  
Marlies Wagner ◽  
Nina Brawanski ◽  
Volker Seifert ◽  
Stefan Wanderer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Subarachnoid Hemorrhage ◽  
Clinical Outcome ◽  
Lower Risk ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Experimental Studies ◽  
Delayed Cerebral Ischemia ◽  
Statin Treatment ◽  
Favorable Outcome ◽  
Simvastatin Treatment

The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in non-aneurysmal (na)SAH in accordance with animal research data illustrating the pathophysiology of naSAH. We systematically searched PubMed using PRISMA-guidelines and selected experimental studies assessing the statin-effect on SAH. Detecting the accordance of the applied experimental models with the pathophysiology of naSAH, we analyzed our institutional database of naSAH patients between 1999 and 2018, regarding the effect of statin treatment in these patients and creating a translational concept. Patient characteristics such as statin-treatment (simvastatin 40 mg/d), the occurrence of cerebral vasospasm (CVS), delayed infarction (DI), delayed cerebral ischemia (DCI), and clinical outcome were recorded. In our systematic review of experimental studies, we found 13 studies among 18 titles using blood-injection-animal-models to assess the statin-effect in accordance with the pathophysiology of naSAH. All selected studies differ on study-setting concerning drug-administration, evaluation methods, and neurological tests. Patients from the Back to Bedside project, including 293 naSAH-patients and 51 patients with simvastatin-treatment, were recruited for this analysis. Patients under treatment were affected by a significantly lower risk of CVS (p < 0.01; OR 3.7), DI (p < 0.05; OR 2.6), and DCI (p < 0.05; OR 3). Furthermore, there was a significant association between simvastatin-treatment and favorable-outcome (p < 0.05; OR 3). However, dividing patients with statin-treatment in pre-SAH (n = 31) and post-SAH (n = 20) treatment groups, we only detected a tenuously significant higher chance for a favorable outcome (p < 0.05; OR 0.05) in the small group of 20 patients with statin post-SAH treatment. Using a multivariate-analysis, we detected female gender (55%; p < 0.001; OR 4.9), Hunt&Hess ≤III at admission (p < 0.002; OR 4), no anticoagulant-therapy (p < 0.0001; OR 0.16), and statin-treatment (p < 0.0001; OR 24.2) as the main factors improving the clinical outcome. In conclusion, we detected a significantly lower risk for CVS, DCI, and DI in naSAH patients under statin treatment. Additionally, a significant association between statin treatment and favorable outcome 6 months after naSAH onset could be confirmed. Nevertheless, unified animal experiments should be considered to create the basis for developing new therapeutic schemes.

Simvastatin for the Prevention of Delayed Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage

US Neurology ◽  
2010 ◽  
Vol 05 (02) ◽  
pp. 58
Author(s):  
Kassi Kronfeld ◽  
Sherry Hsiang-Yi Chou ◽  
◽  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Animal Studies ◽  
Randomized Clinical Trials ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Delayed Cerebral Ischemia ◽  
Delayed Cerebral Vasospasm ◽  
Life Years ◽  
The Us

Aneurysmal subarachnoid hemorrhage (SAH) affects over 30,000 people annually in the US and is responsible for 27% of all stroke-related potential life-years lost before 65 years of age. Delayed cerebral vasospasm, defined as the narrowing of the cerebral arteries at the base of the brain, can occur several days after the initial SAH and cause significant additional morbidity and mortality. Currently, preventive and therapeutic options for delayed cerebral vasospasm are limited and may involve high risk. Oral nimodipine is the only therapeutic agent proven to modestly improve outcome following SAH in multicenter randomized clinical trials. Statins have pleiotropic effects targeting many known pathways in cerebral vasospasm pathogenesis and show promise as potential new therapeutic agents for delayed vasospasm in preliminary animal studies, while results from human data are mixed. In this article, we review the known pathogenic mechanisms of delayed cerebral vasospasm, pre-clinical animal studies on statin use and delayed cerebral vasospasm, and results from human studies to date.

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