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Frontiers in Cardiovascular Medicine 2021Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert...
Myocardial ischemia/reperfusion (I/R) injury is one of the causes of most cardiomyocyte injuries and deaths. Berberine (BBR) has been suggested a potential to exert protective effects against myocardial I/R injury. This systematic review aims to determine the intrinsic mechanisms of BBR's protective effects in myocardial I/R injury. Seven databases were searched for studies performed from inception to July 2020. Methodological quality was assessed by SYRCLE's-RoB tool. Ten studies including a total of 270 animals were included in this study. The methodology quality scores of the included studies ranged from 5 to 7 points. The meta-analysis we conducted demonstrated that BBR significantly reduced myocardial infarct size and the incidence of ventricular arrhythmia, compared to control groups ( < 0.00001). Cardiac function of animals in the BBR treatment group was also markedly increased ( < 0.00001). The index of myocardial apoptosis and the levels of biomarkers of myocardial infarction (LDH and CK) were also decreased in the BBR treatment groups compared to the control groups ( < 0.00001). The pre-clinical evidence, according to our study, showed that BBR is a promising therapeutic agent for myocardial I/R injury. However, this conclusion should be further investigated in clinical studies.
PubMed: 34124190
DOI: 10.3389/fcvm.2021.646306 -
International Journal of Molecular... May 2021Preclinical studies have shown that postconditioning with hydrogen sulfide (HS) exerts cardioprotective effects against myocardial ischemia-reperfusion injury (IRI). The... (Meta-Analysis)
Meta-Analysis Review
Preclinical studies have shown that postconditioning with hydrogen sulfide (HS) exerts cardioprotective effects against myocardial ischemia-reperfusion injury (IRI). The aim of this study was to appraise the current evidence of the cardioprotective effects of HS against IRI in order to explore the future implementation of HS in clinical cardiac transplantation. The current literature on HS postconditioning in the setting of global myocardial ischemia was systematically reviewed and analyzed, performing meta-analyses. A literature search of the electronic databases Medline, Embase and Cinahl identified 1835 studies that were subjected to our pre-defined inclusion criteria. Sixteen studies were considered eligible for inclusion. Postconditioning with HS showed significant robust effects with regard to limiting infarct size (standardized mean difference (SMD) = -4.12, 95% CI [-5.53--2.71], < 0.00001). Furthermore, HS postconditioning consistently resulted in a significantly lower release of cardiac injury markers, lower levels of oxidative stress and improved cardiac function. Postconditioning with slow-releasing HS donors offers a valuable opportunity for novel therapies within cardiac preservation for transplantation. Before clinical implication, studies evaluating the long-term effects of HS treatment and effects of HS treatment in large animal studies are warranted.
Topics: Animals; Biomarkers; Cryopreservation; Heart; Heart Function Tests; Heart Transplantation; Humans; Hydrogen Sulfide; Ischemic Postconditioning; Myocardial Reperfusion Injury; Organ Preservation; Organ Preservation Solutions; Oxidative Stress; Risk Factors; Tissue Donors
PubMed: 34072153
DOI: 10.3390/ijms22115737 -
Frontiers in Cardiovascular Medicine 2021Myocardial ischemia/reperfusion (IR) injury represents a critical problem associated with interventional approaches for coronary reperfusion. Pharmacological...
Myocardial ischemia/reperfusion (IR) injury represents a critical problem associated with interventional approaches for coronary reperfusion. Pharmacological cardioprotective interventions are advocated to ameliorate IR injury. Melatonin is an anti-inflammatory and antioxidant agent with a wide range of therapeutic properties that may contribute to its cardioprotective effects. No systematic review or meta-analysis has compared melatonin vs. placebo as a cardioprotective agent in humans. The present study, based on a systematic review and meta-analysis, was carried out to assess melatonin's efficacy as a cardioprotective treatment. We performed a systematic review of the available literature. Randomized controlled trials (RCTs) were identified and information was extracted using predefined data extraction forms. The primary outcomes were (a) left ventricular ejection fraction (LVEF) and (b) blood troponin levels in patients who underwent myocardial revascularization and were randomized to melatonin or placebo. The inverse-variance random-effects method was used to pool the estimates. Heterogeneity and publication bias were assessed. Weighted mean differences or standardized mean differences were calculated. A total of 283 records were screened and seven RCTs met all the inclusion criteria. After the pooled analysis, the results on LVEF were consistent across all studies, and a significant heterogeneity was found in the results on troponin levels. The melatonin-treated patients had on average higher LVEF than the placebo-treated individuals with a weighted mean difference = 3.1% (95% CI 0.6-5.5, = 0.01). Five works compared the levels of troponin after melatonin or placebo treatment. The melatonin-treated patients had lower levels of troponin with a standardized mean difference = -1.76 (95% CI -2.85 to -0.67, = 0.002). The findings of this meta-analysis revealed that melatonin administration in humans as a cardioprotective agent attenuated heart dysfunction with a favorable effect on the LVEF.
PubMed: 34055929
DOI: 10.3389/fcvm.2021.635083 -
Journal of Cardiothoracic Surgery May 2021The myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via...
The myocardial infarction is the main cause of morbidity and mortality in cardiovascular diseases around the world. Although the timely and complete reperfusion via Percutaneous Coronary Intervention (PCI) or thrombolysis have distinctly decreased the mortality of myocardial infarction, reperfusion itself may lead to supererogatory irreversible myocardial injury and heart function disorders, namely ischemia-reperfusion (I/R) injury. Extensive studies have indicated that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), play important roles in the progress of myocardial I/R injury, which is closely correlative with cardiomyocytes autophagy. Moreover, autophagy plays an important role in maintaining homeostasis and protecting cells in the myocardial ischemia reperfusion and cardiomyocyte hypoxia-reoxygenation (H/R) progress. In this review, we first introduced the biogenesis and functions of ncRNAs, and subsequently summarized the roles and relevant molecular mechanisms of ncRNAs regulating autophagy in myocardial I/R injury. We hope that this review in addition to develop a better understanding of the physiological and pathological roles of ncRNAs, can also lay a foundation for the therapies of myocardial I/R injury, and even for other related cardiovascular diseases.
Topics: Animals; Autophagy; Humans; MicroRNAs; Myocardial Reperfusion Injury; RNA, Circular; RNA, Long Noncoding
PubMed: 34022925
DOI: 10.1186/s13019-021-01524-9 -
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 -
Frontiers in Pharmacology 2021Danhong injections (DHI) are widely used in the treatment of acute myocardial infarction (AMI). As there are no guidelines for the timing of DHI in the... (Review)
Review
Comparison of the Efficacy of Danhong Injections at Different Time-points During the Perioperative Period of Acute Myocardial Infarction: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Danhong injections (DHI) are widely used in the treatment of acute myocardial infarction (AMI). As there are no guidelines for the timing of DHI in the peri-percutaneous coronary intervention (PCI) period for AMI, we investigated the effects of DHI timing. We reviewed reports published before September 30, 2020 in PubMed, embase, the Cochrane Central Register of Controlled Trials, the Chinese BioMedical database, Chinese VIP database, Wanfang database, and Chinese National Knowledge Infrastructure database. Only randomized controlled trials of DHI with percutaneous coronary intervention for AMI were included. Methodological quality was assessed using the Cochrane evaluation manual 5.3.3 criteria. A meta-analysis was performed, and forest plots were drawn. We included 23 studies which all revealed that patients in DHI groups had better efficacy than control groups. Subgroup analysis revealed that DHI administered intraoperatively and continued postoperatively was more effective in increasing left ventricular ejection fraction when compared to other time-points ( < 0.001). The pre- and intraoperative use of DHI could improve reflow more effectively than conventional treatment, while the effect was not significant in the postoperative intervention study ( = 0.654). The 16 postoperative interventions revealed that the effect of DHI at 14 days was better than that at 7 and 10 days for hs-CRP ( = 0.013), the 10-days treatment produced better results for CK-MB than for the other treatments ( < 0.001) and a dosage of 30 ml proved most effective for IL-6 ( < 0.001). DHI proved to be superior to conventional Western medicine in reducing the incidence of adverse cardiac events, promoting reperfusion, improving cardiac function, reducing inflammatory factors, and protecting the myocardium. DHI should be administered early in the perioperative period and continued postoperatively because of its ability to improve cardiac function. Furthermore, in the PCI postoperative, 30 ml is recommended to inhibit IL-6 levels, for patients with high hs-CRP, a course of 14 days is most effective, for patients with obvious abnormalities of CK-MB, a 10-days course of treatment is recommended. However, due to the limited number and quality of the original randomized controlled trials, our conclusions need large, multi-centre RCTs to validation.
PubMed: 33995051
DOI: 10.3389/fphar.2021.643446 -
Free Radical Biology & Medicine Aug 2021Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective... (Review)
Review
Systematic review and network analysis of microRNAs involved in cardioprotection against myocardial ischemia/reperfusion injury and infarction: Involvement of redox signalling.
Although myocardial ischemia-reperfusion injury (I/R) and its pathological consequences are the leading cause of morbidity and mortality worldwide, cardioprotective therapeutics are still not on the market. Oxidative stress, a major contributing factor to myocardial I/R, changes transcription of coding and non-coding RNAs, alters post-transcriptional modulations, and regulate protein function. MicroRNA (miRNA) expression can be altered by oxidative stress and microRNAs may also regulate cytoprotective mechanisms and exert cardioprotection againts I/R. Transcriptomic analysis of I/R and oxidative stress-induced alterations followed by microRNA-mRNA target interaction network analysis may reveal microRNAs and their mRNA targets that may play a role in cardioprotection and serve as microRNA therapeutics or novel molecular targets for further drug development. Here we provide a summary of a systematic literature review and in silico molecular network analysis to reveal important cardioprotective microRNAs and their molecular targets that may provide cardioprotection via regulation of redox signalling.
Topics: Humans; Infarction; MicroRNAs; Myocardial Reperfusion Injury; Oxidation-Reduction; Signal Transduction
PubMed: 33965565
DOI: 10.1016/j.freeradbiomed.2021.04.034 -
BioMed Research International 2021Animal models are well established for studying the effects of alkaloids in preventing myocardial ischemia-reperfusion injury. However, few studies have investigated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal models are well established for studying the effects of alkaloids in preventing myocardial ischemia-reperfusion injury. However, few studies have investigated the therapeutic effects of alkaloids in humans. This meta-analysis and systematic review assessed the efficacy of alkaloids in attenuating infarct size in rats with myocardial ischemia-reperfusion injury.
METHODS
An integrated literature search including the PubMed, Embase, and Cochrane Library databases was performed to identify studies that evaluated the therapeutic effects of alkaloids on myocardial ischemia-reperfusion injury in rats. The main outcome was infarct size, and SYRCLE's risk of bias tool was used to assess the quality of the studies.
RESULTS
22 studies were brought into the meta-analysis. Compared with the effects of vehicle, alkaloids significantly reduced infarct size (standardized mean difference (SMD) = -0.45; 95% confidence interval (CI) = -0.64 to - 0.26). In subgroup analyses, isoquinoline alkaloids (SMD = -0.43; 95%CI = -0.70 to - 0.16) significantly reduced infarct size versus the control.
CONCLUSION
Isoquinoline alkaloids can potentially alleviate myocardial ischemia-reperfusion injury. This meta-analysis and systematic review supply a reference for research programs aiming to develop alkaloid-based clinical drugs. This trial is registered with CRD42019135489.
Topics: Alkaloids; Animals; Disease Models, Animal; Myocardial Reperfusion Injury; Rats
PubMed: 33791371
DOI: 10.1155/2021/6661526 -
Pharmacological Reviews Apr 2021The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the...
The complement system was discovered at the end of the 19th century as a heat-labile plasma component that "complemented" the antibodies in killing microbes, hence the name "complement." Complement is also part of the innate immune system, protecting the host by recognition of pathogen-associated molecular patterns. However, complement is multifunctional far beyond infectious defense. It contributes to organ development, such as sculpting neuron synapses, promoting tissue regeneration and repair, and rapidly engaging and synergizing with a number of processes, including hemostasis leading to thromboinflammation. Complement is a double-edged sword. Although it usually protects the host, it may cause tissue damage when dysregulated or overactivated, such as in the systemic inflammatory reaction seen in trauma and sepsis and severe coronavirus disease 2019 (COVID-19). Damage-associated molecular patterns generated during ischemia-reperfusion injuries (myocardial infarction, stroke, and transplant dysfunction) and in chronic neurologic and rheumatic disease activate complement, thereby increasing damaging inflammation. Despite the long list of diseases with potential for ameliorating complement modulation, only a few rare diseases are approved for clinical treatment targeting complement. Those currently being efficiently treated include paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica spectrum disorders. Rare diseases, unfortunately, preclude robust clinical trials. The increasing evidence for complement as a pathogenetic driver in many more common diseases suggests an opportunity for future complement therapy, which, however, requires robust clinical trials; one ongoing example is COVID-19 disease. The current review aims to discuss complement in disease pathogenesis and discuss future pharmacological strategies to treat these diseases with complement-targeted therapies. SIGNIFICANCE STATEMENT: The complement system is the host's defense friend by protecting it from invading pathogens, promoting tissue repair, and maintaining homeostasis. Complement is a double-edged sword, since when dysregulated or overactivated it becomes the host's enemy, leading to tissue damage, organ failure, and, in worst case, death. A number of acute and chronic diseases are candidates for pharmacological treatment to avoid complement-dependent damage, ranging from the well established treatment for rare diseases to possible future treatment of large patient groups like the pandemic coronavirus disease 2019.
Topics: COVID-19; Collectins; Complement Activating Enzymes; Complement C3; Complement Inactivating Agents; Complement System Proteins; Genetic Therapy; Humans; Inflammation Mediators; Lectins; Mannose-Binding Protein-Associated Serine Proteases; Pandemics; Rare Diseases; SARS-CoV-2; Synapses; Ficolins
PubMed: 33687995
DOI: 10.1124/pharmrev.120.000072 -
Journal of Thrombosis and Thrombolysis Oct 2021Coronavirus disease 2019 (COVID-19) can cause a wide range of cardiovascular diseases, including ST-segment elevation myocardial infarction (STEMI) and STEMI-mimickers...
Coronavirus disease 2019 (COVID-19) can cause a wide range of cardiovascular diseases, including ST-segment elevation myocardial infarction (STEMI) and STEMI-mimickers (such as myocarditis, Takotsubo cardiomyopathy, among others). We performed a systematic review to summarize the clinical features, management, and outcomes of patients with COVID-19 who had ST-segment elevation. We searched electronic databases from inception to September 30, 2020 for studies that reported clinical data about COVID-19 patients with ST-segment elevation. Differences between patients with and without obstructive coronary artery disease (CAD) on coronary angiography were evaluated. Forty-two studies (35 case reports and seven case series) involving 161 patients were included. The mean age was 62.7 ± 13.6 years and 75% were men. The most frequent symptom was chest pain (78%). Eighty-three percent of patients had obstructive CAD. Patients with non-obstructive CAD had more diffuse ST-segment elevation (13% versus 1%, p = 0.03) and diffuse left ventricular wall-motion abnormality (23% versus 3%, p = 0.02) compared to obstructive CAD. In patients with previous coronary stent (n = 17), the 76% presented with stent thrombosis. In the majority of cases, the main reperfusion strategy was primary percutaneous coronary intervention instead of fibrinolysis. The in-hospital mortality was 30% without difference between patients with (30%) or without (31%) obstructive CAD. Our data suggest that a relatively high proportion of COVID-19 patients with ST-segment elevation had non-obstructive CAD. The prognosis was poor across groups. However, our findings are based on case reports and case series that should be confirmed in future studies.
Topics: Aged; COVID-19; Coronary Artery Disease; Female; Hospital Mortality; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Risk Assessment; Risk Factors; ST Elevation Myocardial Infarction; Stents; Thrombolytic Therapy; Time Factors; Treatment Outcome
PubMed: 33646500
DOI: 10.1007/s11239-021-02411-9