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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 -
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 -
International Journal of Cardiology May 2011Patients with ST elevation acute myocardial infarction (STEMI) have different outcome depending on the reperfusion strategy. (Review)
Review
BACKGROUND
Patients with ST elevation acute myocardial infarction (STEMI) have different outcome depending on the reperfusion strategy.
METHODS
To discern if the presence of initial Q waves in the infarct leads is a useful prognostic parameter in STEMI patients within 6 h of symptom onset treated by different reperfusion strategies (fibrinolysis, fibrinolysis followed by percutaneous coronary intervention [PCI], and primary PCI) we performed a systematic review on outcome comparing patients with and without initial Q waves.
RESULTS
The relative risks for those with Q waves were significantly raised for both mortality and the composite outcome of mortality, congestive heart failure or cardiogenic shock, and at both 30-day and 90-day time points. The relative risk for mortality varied from 2.18 (95% CI 1.32-3.61) at 30 days to 2.54 (95% CI 1.87-3.44) at 90 days. The relative risk for composite outcome was 2.28 (95% CI 1.71-3.04) at 30 days and 2.25 (95% CI 1.81-2.80) at 90 days.
CONCLUSION
The presence of initial Q waves is a relatively robust parameter to stratify outcome regardless of the reperfusion methods.
Topics: Angioplasty, Balloon, Coronary; Animals; Electrocardiography; Fibrinolysis; Humans; Myocardial Infarction; Myocardial Reperfusion; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 20004987
DOI: 10.1016/j.ijcard.2009.11.013 -
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 -
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 -
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 -
Critical Care Medicine Sep 2016Noble gases have been attributed to organ protective effects in ischemia reperfusion injury in a variety of medical conditions, including cerebral and cardiac ischemia,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Noble gases have been attributed to organ protective effects in ischemia reperfusion injury in a variety of medical conditions, including cerebral and cardiac ischemia, acute kidney injury, and transplantation. The aim of this study was to appraise the available evidence by systematically reviewing the literature and performing meta-analyses.
DATA SOURCES
PubMed, EMBASE, and the Cochrane Library.
STUDY SELECTION
Inclusion criteria specified any articles on noble gases and either ischemia reperfusion injury or transplantation. In vitro studies, publications without full text, review articles, and letters were excluded.
DATA EXTRACTION
Information on noble gas, organ, species, model, length of ischemia, conditioning and noble gas dose, duration of administration of the gas, endpoints, and effects was extracted from 79 eligible articles. Study quality was evaluated using the Jadad scale. Effect sizes were extracted from the articles or retrieved from the authors to allow meta-analyses using the random-effects approach.
DATA SYNTHESIS
Argon has been investigated in cerebral, myocardial, and renal ischemia reperfusion injury; helium and xenon have additionally been tested in hepatic ischemia reperfusion injury, whereas neon was only explored in myocardial ischemia reperfusion injury. The majority of studies show a protective effect of these noble gases on ischemia reperfusion injury across a broad range of experimental conditions, organs, and species. Overall study quality was low. Meta-analysis for argon was only possible in cerebral ischemia reperfusion injury and did not show neuroprotective effects. Helium proved neuroprotective in rodents and cardioprotective in rabbits, and there were too few data on renal ischemia reperfusion injury. Xenon had the most consistent effects, being neuroprotective in rodents, cardioprotective in rodents and pigs, and renoprotective in rodents.
CONCLUSIONS
Helium and xenon show organ protective effects mostly in small animal ischemia reperfusion injury models. Additional information on timing, dosing, and comparative efficacy of the different noble gases, as well as confirmation in large animal models, is needed before designing clinical trials.
Topics: Animals; Humans; Noble Gases; Reperfusion Injury
PubMed: 27071065
DOI: 10.1097/CCM.0000000000001717 -
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 -
Journal of Anesthesia Feb 2022Cardiopulmonary bypass (CPB) technology provides potential for cardiac surgery, but it is followed by myocardial injury and inflammation related to ischemia-reperfusion.... (Meta-Analysis)
Meta-Analysis Review
Myocardial protective and anti-inflammatory effects of dexmedetomidine in patients undergoing cardiovascular surgery with cardiopulmonary bypass: a systematic review and meta-analysis.
Cardiopulmonary bypass (CPB) technology provides potential for cardiac surgery, but it is followed by myocardial injury and inflammation related to ischemia-reperfusion. This meta-analysis aimed to systematically evaluate the cardioprotective effect of dexmedetomidine on cardiac surgery under CPB and its effect on accompanied inflammation. PubMed, Cochrane Library, EMBASE and Web of Science databases were comprehensively searched for all randomized controlled trials (RCTs) published before April 1st, 2021 that explored the application of dexmedetomidine in cardiac surgery. Compared with the control group (group C), the concentrations of CK-MB in the perioperative period and cTn-I at 12 h and 24 h after operation in dexmedetomidine group (group D) were significantly decreased (P < 0.05). In addition, in group D, the levels of interleukin-6 at 24 h after operation, tumor necrosis factor-a at the 12 h and 24 h after operation were significantly decreased (P < 0.05). At the same time, the length of Intensive Care Unit stay in group D was significantly shorter than group C (P < 0.05). However, there was no significant difference in interleukin-10 level, C reactive protein level, the time on ventilator and length of hospital stay between the two groups (P > 0.05). The application of dexmedetomidine in cardiac surgery with CPB can reduce CK-MB and cTn-I concentration and interleukin-6, tumor necrosis factor-α levels to a certain extent and shorten the length of Intensive Care Unit stay, but it has no significant effect on IL-10 level, C reactive protein level, the time on ventilator and length of hospital stay.
Topics: Anti-Inflammatory Agents; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Dexmedetomidine; Humans; Length of Stay
PubMed: 34342722
DOI: 10.1007/s00540-021-02982-0 -
American Heart Journal Oct 2014Evidence suggests that ischemic postconditioning (IPoC) may reduce the extent of reperfusion injury. We performed a meta-analysis of randomized controlled trials, which... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Evidence suggests that ischemic postconditioning (IPoC) may reduce the extent of reperfusion injury. We performed a meta-analysis of randomized controlled trials, which compared the role of IPoC during primary percutaneous coronary intervention (PCI) to PCI alone (control group) in ST-segment elevation myocardial infarction.
METHODS
Several databases were searched, which yielded 19 studies. The outcomes of interest were measures of myocardial damage (serum cardiac enzymes and infarct size by imaging) and left ventricular function (left ventricular ejection fraction and wall motion score index). Mean difference (MD) and standardized mean difference (SMD) were used to assess the treatment effect. An inverse variance method was used to pool data into a random-effects model.
RESULTS
Ischemic postconditioning demonstrated a decrease in serum cardiac enzymes (SMD -0.48, 95% CI -0.92 to -0.05, I(2) = 92%), reduction in infarct size by imaging (SMD -0.30, 95% CI -0.58 to -0.01, I(2) = 80%), wall motion score index (MD -0.19, 95% CI -0.29 to -0.09, I(2) = 44%), and showed improvement in left ventricular ejection fraction (IPoC 52 ± 0.4, control 49.7 ± 0.4) (MD 2.78, 95% CI 0.66-4.91, I(2) = 69%). All included studies were limited by high risk of performance and publication bias.
CONCLUSIONS
Ischemic postconditioning during PCI in ST-segment elevation myocardial infarction appears to be superior to PCI alone in reduction of both myocardial injury or damage and improvement in global and regional left ventricular function. The effect seems to be more pronounced when a greater myocardial area is at risk. Given the limitations of the current available evidence, additional data from large randomized controlled trials are warranted.
Topics: Electrocardiography; Humans; Ischemic Postconditioning; Myocardial Infarction; Treatment Outcome
PubMed: 25262261
DOI: 10.1016/j.ahj.2014.06.021