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Journal of Pharmaceutical Policy and... Aug 2023Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and... (Review)
Review
BACKGROUND
Acute coronary syndrome (ACS) is the principal cause of death in developing countries including Ethiopia. No study reports the overall patterns of risk factors and burden of in-hospital mortality in Ethiopia. This study, therefore, aimed to assess the magnitude of risk factors, management, and in-hospital mortality of ACS in Ethiopia.
METHODS
Electronic searching of articles was conducted using PubMed, Science Direct, EMBASE, Scopus, Hinari, and Google Scholar to access articles conducted in Ethiopia. The Preferred Reporting Items for Systematic Reviews checklist was used for identification, eligibility screening, and selection of articles. Data were extracted with an abstraction form prepared with Microsoft Excel and exported to STATA for analysis. Funnel plot, Begg's test, and Egger's test were used to determine publication bias. Heterogeneity between the studies was checked by I statistic. The pooled prevalence of risk factors and in-hospital mortality of ACS were estimated using a random-effects meta-analysis model.
RESULTS
Most (59.367%) of the patients had ST-segment elevation myocardial infarction (STEMI). Hypertension (54.814%) was the leading risk factor for ACS followed by diabetes mellitus (38.549%). Aspirin (56.903%) and clopidogrel (55.266%) were most frequently used in patients with STEMI ACS, respectively. The pooled proportion of in-hospital mortality of ACS was 14.82% which was higher in patients with STEMI (16.116%).
CONCLUSION
The rate of in-hospital mortality is still high which was higher in patients with STEMI. Initiation of treatment must consider the heterogeneity of each patient's risk factor and reperfusion therapy should be implemented in our setting.
PubMed: 37550741
DOI: 10.1186/s40545-023-00603-7 -
Phytomedicine : International Journal... Jul 2022The primary therapeutic strategy in managing ischemic heart diseases is to restore the perfusion of the myocardial ischemic area by surgical methods that often result in... (Review)
Review
BACKGROUND
The primary therapeutic strategy in managing ischemic heart diseases is to restore the perfusion of the myocardial ischemic area by surgical methods that often result in an unavoidable injury called ischemia-reperfusion injury (IR). Fisetin is an effective flavonoid with antioxidant and anti-inflammatory properties, proven to be cardioprotective against IR injury in both in-vitro and invivo models, apart from its promising health benefits against cancer, diabetes, and neurodegenerative ailments.
PURPOSE
The potential of fisetin in attenuating myocardial IR is inconclusive as the effectiveness of fisetin needs more understanding in terms of its possible target sites and underlying different mechanisms. Considering the surge in recent scientific interests in fisetin as a pharmacological agent, this review not only updates the existing preclinical and clinical studies with fisetin and its underlying mechanisms but also summarizes its possible targets during IR protection.
METHODS
We performed a literature survey using search engines Pubmed, PMC, Science direct, Google, and research gate published across the years 2006-2021. The relevant studies were extracted from the databases with the combinations of the following keywords and summarized: myocardial ischemia-reperfusion injury, natural products, flavonoid, fisetin, PI3K, JAK-STAT, Nrf2, PKC, JNK, autophagy.
RESULTS
Fisetin is reported to be effective in attenuating IR injury by delaying the clotting time, preserving the mitochondrial function, reducing oxidative stress, and inhibiting GSK 3β. But it failed to protect diseased cardiomyocytes challenged to IR. As discussed in the current review, fisetin not only acts as a conventional antioxidant and anti-inflammatory agent to exert its biological effect but may also exert modulatory action on the cellular metabolism and adaptation via direct action on various signalling pathways that comprise PI3K, JAK-STAT, Nrf2, PKC, JNK, and autophagy. Moreover, the dosage of fisetin and co-morbidities like diabetes and obesity are found to be detrimental factors for cardioprotection.
CONCLUSION
For further evaluation and smooth clinical translation of the fisetin molecule in IR treatment, researchers should pay close attention to the potential of fisetin to possibly alter the key cardioprotective pathways and dosage, as the efficacy of fisetin is tissue and cell type-specific and varies with different doses.
Topics: Antioxidants; Flavonoids; Flavonols; Humans; Myocardial Reperfusion Injury; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases
PubMed: 35533608
DOI: 10.1016/j.phymed.2022.154123 -
Frontiers in Cardiovascular Medicine 2022At present, effective clinical therapies for myocardial ischemia-reperfusion injury (MIRI) are lacking. We investigated if luteolin conferred cardioprotective effects...
BACKGROUND
At present, effective clinical therapies for myocardial ischemia-reperfusion injury (MIRI) are lacking. We investigated if luteolin conferred cardioprotective effects against MIRI and elucidated the potential underlying mechanisms.
METHOD
Four databases were searched for preclinical studies of luteolin for the treatment of MIRI. The primary outcomes were myocardial infarct size (IS) and intracardiac hemodynamics. The second outcomes were representative indicators of apoptosis, oxidative stress, and inflammatory. The Stata and RevMan software packages were utilized for data analysis.
RESULTS
Luteolin administration was confirmed to reduce IS and ameliorate hemodynamics as compared to the control groups ( < 0.01). IS had decreased by 2.50%, 2.14%, 2.54% in three subgroups. Amelioration of hemodynamics was apparent in two different myocardial infarct models (model of left anterior descending branch ligation and model of global heart ischemia), as left ventricular systolic pressure improved by 21.62 and 35.40 mmHg respectively, left ventricular end-diastolic pressure decreased by 7.79 and 4.73 mmHg respectively, maximum rate of left ventricular pressure rise increased by 737.48 and 750.47 mmHg/s respectively, and maximum rate of left ventricular pressure decrease increased by 605.66 and 790.64 mmHg/s respectively. Apoptosis of cardiomyocytes also significantly decreased, as indicated by thelevels of MDA, an oxidative stress product, and expression of the inflammatory factor TNF-α ( < 0.001).
CONCLUSION
Pooling of the data demonstrated that luteolin exerts cardioprotective effects against MIRI through different signaling pathways. As possible mechanisms, luteolin exerts anti-apoptosis, anti-oxidation, and anti-inflammation effects against MIRI.
PubMed: 35548432
DOI: 10.3389/fcvm.2022.685998 -
Journal of Translational Medicine May 2021Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their... (Review)
Review
BACKGROUND
Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation.
METHODS
We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis.
RESULTS
Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery.
CONCLUSION
The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.
Topics: Animals; Cell Death; Child; Humans; Mitochondria; Reperfusion Injury
PubMed: 34001191
DOI: 10.1186/s12967-021-02878-3 -
Current Pharmaceutical Biotechnology Jan 2024Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
BACKGROUND
Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function.
OBJECTIVES
This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs.
METHODS
This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel.
RESULTS
Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-κB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs.
CONCLUSION
Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.
PubMed: 38310454
DOI: 10.2174/0113892010281821240102105415 -
Arquivos Brasileiros de Cardiologia Dec 2022Most cardiovascular deaths occur in low- and middle-income countries and myocardial infarction is one of the main life-threatening conditions. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Most cardiovascular deaths occur in low- and middle-income countries and myocardial infarction is one of the main life-threatening conditions.
OBJECTIVE
We assessed all-cause in-hospital mortality in patients admitted for myocardial infarction (STEMI and NSTEMI) in Latin America and the Caribbean from 2000 onward.
METHODS
We systematically searched in electronic bibliographic databases for cohort studies which reported in-hospital mortality due to STEMI and NSTEMI. A meta-analysis was performed and a p-value < 0.05 was considered significant.
RESULTS
We identified 38 studies (29 STEMI, 3 NSTEMI and 6 both). Pooled STEMI in-hospital mortality was 9.9% (95% CI: 9.1 - 10.7). Heterogeneity was not trivial (I2 = 74% and prediction interval = 6.6 - 14.5). The percentage of reperfusion therapy and decade explain part of the heterogeneity (I2 = 54%). The higher the rate of reperfusion therapy, the lower the in-hospital mortality (coefficient = -0.009, 95% CI: -0.013 to -0.006, p<0.001). This mortality was higher in the first decade as compared with the second (coefficient = -0.14, 95% CI: -0.27 to -0.02, p=0.047). Pooled NSTEMI in-hospital mortality was 6.3% (95% CI: 5.4 - 7.4) and heterogeneity was null.
CONCLUSION
Pooled STEMI in-hospital mortality in low- and middle-income countries was high in comparison with rates reported in high income countries. To improve these estimates, higher use of reperfusion therapy must be pursued. Pooled NSTEMI in-hospital mortality was similar to the ones found in high-income countries; however, it was based on few studies and most of them were carried out in two countries.
Topics: Humans; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction; Hospital Mortality; Latin America; Caribbean People; Myocardial Infarction; Risk Factors
PubMed: 36541993
DOI: 10.36660/abc.20220194 -
Frontiers in Cardiovascular Medicine 2022Myocardial ischemia/reperfusion injury (IRI) is a common and serious complication in clinical practice. Sevoflurane conditionings have been identified to provide a...
OBJECTIVE
Myocardial ischemia/reperfusion injury (IRI) is a common and serious complication in clinical practice. Sevoflurane conditionings have been identified to provide a protection against myocardial IRI in animal experiments, but their true clinical benefits remain controversial. Here, we aimed to analyze the preclinical evidences obtained in animal models of myocardial IRI and explore the possible reasons for controversial clinical benefits.
METHODS
Our primary outcome was the difference in mean infarct size between the sevoflurane and control groups in animal models of myocardial IRI. After searching the databases of PubMed, Embase, Web of Science, and the Cochrane Library, a systematic review retrieved 37 eligible studies, from which 28 studies controlled comparisons of sevoflurane preconditioning (SPreC) and 40 studies controlled comparisons of sevoflurane postconditioning (SPostC) that were made in a pooled random-effects meta-analysis. In total, this analysis included data from 313 control animals and 536 animals subject to sevoflurane conditionings.
RESULTS
Pooled estimates for primary outcome demonstrated that sevoflurane could significantly reduce the infarct size after myocardial IRI whether preconditioning [weighted mean difference (WMD): -18.56, 95% CI: -23.27 to -13.85, < 0.01; = 94.1%, < 0.01] or postconditioning (WMD: -18.35, 95% CI: -20.88 to -15.83, < 0.01; = 90.5%, < 0.01) was performed. Interestingly, there was significant heterogeneity in effect size that could not be explained by any of the prespecified variables by meta-regression and stratified analysis. However, sensitivity analysis still identified the cardioprotective benefits of sevoflurane conditionings with robust results.
CONCLUSION
Sevoflurane conditionings can significantly reduce infarct size in models of myocardial IRI. Given the fact that there is a lack of consistency in the quality and design of included studies, more well-performed studies with the detailed characterization of sevoflurane protocols, especially studies in larger animals regarding cardioprotection effects of sevoflurane, are still required.
PubMed: 35571167
DOI: 10.3389/fcvm.2022.841654 -
Cureus Aug 2023Myocardial infarction (MI) is a significant cause of morbidity and mortality in low- and middle-income countries. Fibrinolytic agents and percutaneous coronary... (Review)
Review
Myocardial infarction (MI) is a significant cause of morbidity and mortality in low- and middle-income countries. Fibrinolytic agents and percutaneous coronary intervention (PCI) are the main approaches for the recanalization and reperfusion of the myocardium following MI. Many studies have shown that PCI is superior to thrombolytics due to better outcomes and decreased mortality. Nevertheless, PCI's mortality gain over thrombolysis decreases as the time between presentation and PCI procedure increases. Furthermore, PCI is not widely available in most developing countries; thus, it cannot be delivered promptly. Most patients in developing countries cannot afford the cost of PCI. Thus, thrombolytic therapy remains essential to managing MI in developing countries and should not be disregarded. Tenecteplase (TNK) and streptokinase (SK) are the two most widely used fibrinolytics in managing MI in underdeveloped nations. Despite their widespread availability, comparative studies on them have been inconclusive. This study aims to review the available literature on the effectiveness and safety of TNK versus SK in managing MI in resource-poor nations. The study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) extension and analyzed according to Cochrane guidelines on synthesis without meta-analysis. A comprehensive literature search for studies comparing TNK and STK was conducted on EMBASE, Cochrane Library, Web of Science, CINAHL, Scopus, Google Scholar, and Ovid version of MEDLINE databases. A reference list of the eligible articles and systematic reviews was also screened. A narrative synthesis of the available data was done by representing the data on the effect direction plot, followed by vote counting. Of the 2284 references retrieved from the databases, only 17 studies met the inclusion criteria and were selected for final analysis. The study suggested that TNK is more effective in complete ST-segment resolution (80% vs 10% on the effect direction plot) and symptom relief (80% vs 20%) than SK. SK and TNK were comparable in achieving successful fibrinolysis (50% vs 50%). For the safety parameters, TNK is associated with a lesser risk of major bleeding than SK (88.9% vs 11.1%) and minor bleeding (25% vs 75%). SK was linked with a higher risk of hypotension/shock (77.8% vs 11.1%) and anaphylaxis/allergy (100% vs 0%). Long-term mortality was higher in the SK arm (100% vs 0%). In-hospital mortality is comparable between the two agents (37.5% vs 37.5%). There is conflicting evidence regarding other safety and efficacy endpoints. Compared to SK, TNK results in better complete ST-segment resolution and symptom relief. A higher risk of long-term mortality, increased risk of major and minor bleeding, hypotension, and allergy/anaphylaxis was observed in patients who received SK. Both agents were comparable in terms of in-hospital mortality and successful fibrinolysis. Controversy exists regarding which agent is linked with increased risk of 30-35-day mortality benefit and stroke. Randomized controlled trials (RCTs) with large sample sizes are needed to establish TNK vs SK superiority in efficacy and safety. The long-term duration of follow-up of the mortality rate of the two agents is also essential, as most patients in these regions cannot afford the recommended PCI post-fibrinolysis.
PubMed: 37750155
DOI: 10.7759/cureus.44125 -
Annals of Translational Medicine Sep 2022Though best known for its immunosuppressant effects, cyclosporine A (CsA) has also been studied as a treatment to mitigate ischemia-reperfusion injury (IRI) by its...
BACKGROUND
Though best known for its immunosuppressant effects, cyclosporine A (CsA) has also been studied as a treatment to mitigate ischemia-reperfusion injury (IRI) by its inhibition of the mitochondria permeability transition pore (mPTP). Despite numerous preclinical studies supporting its benefit in reducing infarct size following myocardial IRI, large randomized controlled clinical trials have been unable to show a beneficial effect. Exploring existing preclinical data can give us the opportunity to revisit some the assumptions that may have led to the failure of these studies to translate clinically. Herein, we present a systematic review of preclinical studies testing CsA to attenuate myocardial IRI (PROSPERO CRD42020159620).
METHODS
We conducted a systematic search of health research databases Ovid MEDLINE, Ovid EMBASE, Web of Science BIOSIS, and Scopus, as well as Cochrane and PROSPERO systematic review databases, on March 9, 2022 for non-human animal studies of myocardial IRI, using CsA as a treatment that reported clinically relevant outcomes. Bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool and a modified Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies checklist. Sub-group meta-analyses were conducted to identify potential factors influencing outcomes.
RESULTS
We identified 71 studies, 59 of which were studies of coronary occlusion. Overall, 75% of studies reported a clear positive effect of CsA in mitigating myocardial IRI by some clinically relevant parameter (e.g., infarct size). A meta-analysis including 43 coronary occlusion studies showed an overall reduction in infarct size with CsA treatment (16.09%; 95% CI: -18.50% to -13.67%). Subgroup meta-analyses identified species, age, timing of administration, and duration of ischemia as factors potentially affecting the efficacy of CsA in the setting of myocardial IRI.
CONCLUSIONS
Our systematic review and meta-analysis identifies questions that have yet to be answered by preclinical studies, highlighting important differences between these and clinical studies that should be addressed prior to proceeding with any further clinical studies using CsA to treat IRI in the heart or other organs. We also use the example of CsA to highlight general considerations for researchers attempting to translate animal studies into the clinical setting.
PubMed: 36267756
DOI: 10.21037/atm-22-618 -
Frontiers in Cardiovascular Medicine 2022Several studies have investigated the combined use of sacubitril- valsartan after reperfusion in acute ST-segment elevation myocardial infarction (STEMI). However, the...
BACKGROUND
Several studies have investigated the combined use of sacubitril- valsartan after reperfusion in acute ST-segment elevation myocardial infarction (STEMI). However, the sample sizes of these studies were small and their results were somewhat heterogeneous. To determine the effect of sacubitril-valsartan on myocardial ischemia-reperfusion.
METHODS
Search PubMed, EMbase, Web of Science and The Cochrane Library, CNKI database, VIP database and Wanfang digital journal full-text database for eligible articles from their date of inception up to April, 2022. All data were meta-analyzed using Review Manager 5.3 and STATA 16.0 software.
RESULTS
A total of 23 studies including 2,326 patients with acute STEMI were included. These results of this meta-analysis indicated that left ventricular ejection fractions (LVEF) value within 6 months after surgery (OR, 4.29; 95% confidence interval, 3.78-4.80; < 0.00001), left ventricular end-diastolic diameter (LVEDD) value within 6 months after surgery (OR, -3.11; 95% CI, -3.87 to -2.35; < 0.00001) and left ventricular end-diastolic volume (LVEDV) value 6 months after operation (OR, -6.22; 95% CI, -7.10 to -5.35; < 0.00001) are better than without sacubitril and valsartan.
CONCLUSION
To sum up the above, the results of this study suggest that sacubitril- valsartan can reduce the reperfusion injury of ischemic myocardium by improving cardiac function within a follow-up period of 6 months.
PubMed: 36531731
DOI: 10.3389/fcvm.2022.1036151