-
Biomedicine & Pharmacotherapy =... May 2024Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical... (Meta-Analysis)
Meta-Analysis Review
Propofol, a commonly used intravenous anesthetic, has demonstrated potential in protecting against myocardial ischemia/reperfusion injury (MIRI) based on preclinical animal studies. However, the clinical benefits of propofol in this context are subject to debate. We conducted a systematic search across eight databases to identify all relevant animal studies investigating the preventive effects of propofol on MIRI until October 30, 2023. We assessed the methodological quality of the included studies using SYRCLE's bias risk tool. Statistical analysis was performed using STATA 15.1. The primary outcome measures analyzed in this study were myocardial infarct size (IS) and myocardial injury biomarkers. This study presents a comprehensive analysis of 48 relevant animal studies investigating propofol's preventive effects on MIRI. Propofol administration demonstrated a reduction in myocardial IS and decreased levels of myocardial injury biomarkers (CK-MB, LDH, cTnI). Moreover, propofol improved myocardial function parameters (+dp/dtmax, -dP/dtmax, LVEF, LVFS), exhibited favorable effects on inflammatory markers (IL-6, TNF-α) and oxidative stress markers (SOD, MDA), and reduced myocardial cell apoptotic index (AI). These findings suggest propofol exerts cardioprotective effects by reducing myocardial injury, decreasing infarct size, and improving heart function. However, the absence of animal models that accurately represent comorbidities such as aging and hypertension, as well as inconsistent administration methods that align with clinical practice, may hinder its clinical translation. Further robust investigations are required to validate these findings, elucidate the underlying mechanisms of propofol, and facilitate its potential translation into clinical practice.
Topics: Propofol; Animals; Myocardial Infarction; Myocardial Reperfusion Injury; Oxidative Stress; Biomarkers; Anesthetics, Intravenous; Humans; Apoptosis
PubMed: 38640712
DOI: 10.1016/j.biopha.2024.116629 -
PloS One 2017Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct... (Meta-Analysis)
Meta-Analysis Review
Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE's risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.
Topics: Animals; In Vitro Techniques; Metformin; Mice; Myocardial Infarction; Rabbits; Rats; Swine
PubMed: 28832637
DOI: 10.1371/journal.pone.0183664 -
Basic Research in Cardiology Mar 2016Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in... (Review)
Review
Unmodified reperfusion therapy for acute myocardial infarction (AMI) is associated with irreversible myocardial injury beyond that sustained during ischemia. Studies in experimental models of ischemia/reperfusion and in humans undergoing reperfusion therapy for AMI have examined potential beneficial effects of nitric oxide (NO) supplemented at the time of reperfusion. Using a rigorous systematic search approach, we have identified and critically evaluated all the relevant experimental and clinical literature to assess whether exogenous NO given at reperfusion can limit infarct size. An inclusive search strategy was undertaken to identify all in vivo experimental animal and clinical human studies published in the period 1990-2014 where NO gas, nitrite, nitrate or NO donors were given to ameliorate reperfusion injury. Articles were screened at title and subsequently at abstract level, followed by objective full text analysis using a critical appraisal tool. In twenty-one animal studies, all NO treatments except nitroglycerin afforded protection against measures of reperfusion injury, including infarct size, creatinine kinase release, neutrophil accumulation and cardiac dysfunction. In three human AMI RCT's, there was no consistent evidence of infarct limitation associated with NO treatment as an adjunct to reperfusion. Despite experimental evidence that most NO treatments can reduce infarct size when given as adjuncts to reperfusion, the value of these interventions in clinical AMI is unproven. Our study raises issues for the design of further clinical studies and emphasises the need for improved design of animal studies to reflect more accurately the comorbidities and other confounding factors seen in clinical AMI.
Topics: Animals; Humans; Myocardial Infarction; Myocardial Reperfusion; Nitric Oxide
PubMed: 26912064
DOI: 10.1007/s00395-016-0540-y -
Oxidative Medicine and Cellular... 2017Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a... (Review)
Review
Ginseng is an important herbal drug that has been used worldwide for many years. Ginsenoside Rb1 (G-Rb1), the major pharmacological extract from ginseng, possesses a variety of biological activities in the cardiovascular systems. Here, we conducted a preclinical systematic review to investigate the efficacy of G-Rb1 for animal models of myocardial ischemia/reperfusion injury and its possible mechanisms. Ten studies involving 211 animals were identified by searching 6 databases from inception to May 2017. The methodological quality was assessed by using the CAMARADES 10-item checklist. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 7 points. Meta-analyses showed that G-Rb1 can significantly decrease the myocardial infarct size and cardiac enzymes (including lactate dehydrogenase, creatine kinase, and creatine kinase-MB) when compared with control group ( < 0.01). Significant decrease in cardiac troponin T and improvement in the degree of ST-segment depression were reported in one study ( < 0.05). Additionally, the possible mechanisms of G-Rb1 for myocardial infarction are antioxidant, anti-inflammatory, antiapoptosis, promoting angiogenesis and improving the circulation. Thus, G-Rb1 is a potential cardioprotective candidate for further clinical trials of myocardial infarction.
Topics: Animals; Disease Models, Animal; Female; Ginsenosides; Male; Myocardial Reperfusion Injury; Panax; Rats
PubMed: 29430282
DOI: 10.1155/2017/6313625 -
Diagnostics (Basel, Switzerland) Nov 2020The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In... (Review)
Review
The complement system has a significant role in myocardial ischemia/reperfusion injury, being responsible for cell lysis and amplification of inflammatory response. In this context, several studies highlight that terminal complement complex C5b-9, also known as the membrane attack complex (MAC), is a significant contributor. The MAC functions were studied by many researchers analyzing the characteristics of its activation in myocardial infarction. Here, a systematic literature review was reported to evaluate the principal features, advantages, and limits (regarding the application) of complement components and MAC in post mortem settings to perform the diagnosis of myocardial ischemia/infarction. The review was performed according to specific inclusion and exclusion criteria, and a total of 26 studies were identified. Several methods studied MAC, and each study contributes to defining better how and when it affects the myocardial damage in ischemic/reperfusion injury. The articles were discussed, focusing on the specificity, sensibility, and post mortem stability of MAC as a marker of myocardial ischemia/infarction, supporting the usefulness in routine post mortem investigations.
PubMed: 33147886
DOI: 10.3390/diagnostics10110898 -
Journal of the American Heart... May 2017Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Remote ischemic conditioning (RIC) is a noninvasive therapeutic strategy that uses brief cycles of blood pressure cuff inflation and deflation to protect the myocardium against ischemia-reperfusion injury. The objective of this systematic review was to determine the impact of RIC on myocardial salvage index, infarct size, and major adverse cardiovascular events when initiated before catheterization.
METHODS AND RESULTS
Electronic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were conducted and reference lists were hand searched. Randomized controlled trials comparing percutaneous coronary intervention (PCI) with and without RIC for patients with ST-segment-elevation myocardial infarction were included. Two reviewers independently screened abstracts, assessed quality of the studies, and extracted data. Data were pooled using random-effects models and reported as mean differences and relative risk with 95% confidence intervals. Eleven articles (9 randomized controlled trials) were included with a total of 1220 patients (RIC+PCI=643, PCI=577). Studies with no events were excluded from meta-analysis. The myocardial salvage index was higher in the RIC+PCI group compared with the PCI group (mean difference: 0.08; 95% confidence interval, 0.02-0.14). Infarct size was reduced in the RIC+PCI group compared with the PCI group (mean difference: -2.46; 95% confidence interval, -4.66 to -0.26). Major adverse cardiovascular events were lower in the RIC+PCI group (9.5%) compared with the PCI group (17.0%; relative risk: 0.57; 95% confidence interval, 0.40-0.82).
CONCLUSIONS
RIC appears to be a promising adjunctive treatment to PCI for the prevention of reperfusion injury in patients with ST-segment-elevation myocardial infarction; however, additional high-quality research is required before a change in practice can be considered.
Topics: Chi-Square Distribution; Extremities; Humans; Ischemic Preconditioning; Myocardial Reperfusion Injury; Myocardium; Odds Ratio; Percutaneous Coronary Intervention; Regional Blood Flow; Risk Factors; ST Elevation Myocardial Infarction; Time Factors; Treatment Outcome
PubMed: 28515120
DOI: 10.1161/JAHA.117.005522 -
Lancet (London, England) Aug 2017Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are... (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of reperfusion therapy with fibrinolytic agents in patients with ST-segment elevation myocardial infarction: a systematic review and network meta-analysis.
BACKGROUND
Fibrinolytic therapy offers an alternative to mechanical reperfusion for ST-segment elevation myocardial infarction (STEMI) in settings where health-care resources are scarce. Comprehensive evidence comparing different agents is still unavailable. In this study, we examined the effects of various fibrinolytic drugs on clinical outcomes.
METHODS
We did a network meta-analysis based on a systematic review of randomised controlled trials comparing fibrinolytic drugs in patients with STEMI. Several databases were searched from inception up to Feb 28, 2017. We included only randomised controlled trials that compared fibrinolytic agents as a reperfusion therapy in adult patients with STEMI, whether given alone or in combination with adjunctive antithrombotic therapy, against other fibrinolytic agents, a placebo, or no treatment. Only trials investigating agents with an approved indication of reperfusion therapy in STEMI (streptokinase, tenecteplase, alteplase, and reteplase) were included. The primary efficacy outcome was all-cause mortality within 30-35 days and the primary safety outcome was major bleeding. This study is registered with PROSPERO (CRD42016042131).
FINDINGS
A total of 40 eligible studies involving 128 071 patients treated with 12 different fibrinolytic regimens were assessed. Compared with accelerated infusion of alteplase with parenteral anticoagulants as background therapy, streptokinase and non-accelerated infusion of alteplase were significantly associated with an increased risk of all-cause mortality (risk ratio [RR] 1·14 [95% CI 1·05-1·24] for streptokinase plus parenteral anticoagulants; RR 1·26 [1·10-1·45] for non-accelerated alteplase plus parenteral anticoagulants). No significant difference in mortality risk was recorded between accelerated infusion of alteplase, tenecteplase, and reteplase with parenteral anticoagulants as background therapy. For major bleeding, a tenecteplase-based regimen tended to be associated with lower risk of bleeding compared with other regimens (RR 0·79 [95% CI 0·63-1·00]). The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy increased the risk of major bleeding by 1·27-8·82-times compared with accelerated infusion alteplase plus parenteral anticoagulants (RR 1·47 [95% CI 1·10-1·98] for tenecteplase plus parenteral anticoagulants plus glycoprotein inhibitors; RR 1·88 [1·24-2·86] for reteplase plus parenteral anticoagulants plus glycoprotein inhibitors).
INTERPRETATION
Significant differences exist among various fibrinolytic regimens as reperfusion therapy in STEMI and alteplase (accelerated infusion), tenecteplase, and reteplase should be considered over streptokinase and non-accelerated infusion of alteplase. The addition of glycoprotein IIb or IIIa inhibitors to fibrinolytic therapy should be discouraged.
FUNDING
None.
Topics: Female; Fibrinolytic Agents; Hemorrhage; Humans; Male; Middle Aged; Myocardial Reperfusion; Network Meta-Analysis; Patient Safety; Risk Factors; ST Elevation Myocardial Infarction; Stroke; Treatment Outcome
PubMed: 28831992
DOI: 10.1016/S0140-6736(17)31441-1 -
Frontiers in Pharmacology 2023Tanshinone IIA (Tan IIA), the major active lipophilic ingredient of , exerts various therapeutic effects on the cardiovascular system. We aimed to identify the...
Tanshinone IIA (Tan IIA), the major active lipophilic ingredient of , exerts various therapeutic effects on the cardiovascular system. We aimed to identify the preclinical evidence and possible mechanisms of Tan IIA as a cardioprotective agent in the treatment of myocardial ischemia/reperfusion injury. The study quality scores of twenty-eight eligible studies and data analyses were separately assessed using the CAMARADES 10-item checklist and Rev-Man 5.3 software. The study quality score ranged from 3/10 to 7/10 points. The present study provided preliminary preclinical evidence that Tan IIA could significantly decrease the myocardial infarct size, cardiac enzyme activity and troponin levels compared with those in the control group (). Tan IIA alleviated myocardial I/R injury via antioxidant, anti-inflammatory, anti-apoptosis mechanisms and improved circulation and energy metabolism. Thus, Tan IIA is a promising cardioprotective agent for the treatment of myocardial ischemia/reperfusion injury and should be further investigated in clinical trials.
PubMed: 37261285
DOI: 10.3389/fphar.2023.1165212 -
American Journal of Cardiovascular... 2021Admission hyperglycemia (AH) is a common finding in patients with acute coronary syndrome and has been reported to be associated with increased morbidity and mortality....
Admission hyperglycemia is associated with reperfusion failure in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: a systematic review and meta-analysis.
BACKGROUND
Admission hyperglycemia (AH) is a common finding in patients with acute coronary syndrome and has been reported to be associated with increased morbidity and mortality. Prior studies suggest that AH could be associated with reperfusion failure. We conducted a systematic review and meta-analysis to explore an association between AH and risk of reperfusion failure in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).
METHODS
Two investigators searched the databases of MEDLINE and EMBASE from inception to February 2021. Study eligibility was independently determined by two investigators and needed to demonstrate association of AH and rate of reperfusion failure, or sufficient raw data to calculate the effect size. Participants were classified into two groups corresponding to their level of admission hyperglycemia. Group 1 was defined as an AH of ≥120-150 mg/dl, and group 2 as ≥150-200 mg/dl. Data from each study were combined using the random-effects model, the generic inverse-variance method of Der Simonian and Laird. The heterogeneity of effect size was quantified using the I statistic. A sensitivity analysis was performed by omitting one study at a time. Publication bias was assessed using a funnel plot and the Egger's test. All data analyses were performed using STATA SE version 14.2.
RESULTS
A total of ten studies from 2008 to 2019 met eligibility criteria and were included in the final analysis. We found that AH is associated with increased risk of reperfusion failure in both group 1 (pooled OR=1.78, 95% CI: 1.35-2.33, I=63.2%, P<0.001) and group 2 (pooled OR=1.44, 95% CI: 1.14-1.82, I=57.1%, P<0.001). Sensitivity analysis showed that none of the results were significantly altered after removing one study at a time. In subgroup analysis of non-diabetic patients, we found that AH is also associated with increased risk of reperfusion failure in both group 1 (pooled OR=1.81, 95% CI: 1.29-2.54, P<0.001) and group 2 (pooled OR=1.61, 95% CI: 1.17-2.21, P<0.001). We did not perform a funnel plot or Egger's test as the number of available outcomes was insufficient to reject the assumption of funnel plot asymmetry.
CONCLUSIONS
Our systematic review and meta-analysis demonstrated that AH is associated with increased risk of reperfusion failure in STEMI patients undergoing pPCI, in the non-diabetic population.
PubMed: 34322304
DOI: No ID Found -
American Heart Journal Apr 2013Shorter time to reperfusion is associated with a significant reduction in mortality; however, its association with heart failure (HF) is not clearly documented. We... (Review)
Review
Association of time to reperfusion with left ventricular function and heart failure in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: a systematic review.
BACKGROUND
Shorter time to reperfusion is associated with a significant reduction in mortality; however, its association with heart failure (HF) is not clearly documented. We conducted a systematic review to examine the association between time to reperfusion and incident HF and/or left ventricular dysfunction.
METHODS
MEDLINE/OVID, EMBASE, Cochrane Library, and Web of Science databases were searched from January 1974 to May 2012 for studies that reported the association between time to reperfusion and incident HF or left ventricular ejection fraction (LVEF) in patients undergoing primary percutaneous coronary intervention.
RESULTS
Of 362 nonduplicate abstracts, 71 studies were selected for full-text review. Thirty-three studies were included in the final review, of which 16 were single-center studies, 7 were population-based studies, 7 were subanalyses from randomized controlled trials, and 3 were based on national samples. The pooled data demonstrate that every 1-hour delay in time to reperfusion is associated with a 4% to 12% increased risk of new-onset HF and a 4% relative increase in the risk of incident HF during follow-up. Early reperfusion was associated with a 2% to 8% greater LVEF before discharge and a 3% to 12% larger improvement in absolute LVEF at follow-up compared with the index admission.
CONCLUSIONS
This systematic review presents evidence that longer time to reperfusion is not only associated with worsened left ventricular systolic function and new-onset HF at the time of index admission, but also with increased risk of HF and reduced improvement in left ventricular systolic function during follow-up.
Topics: Comorbidity; Heart Failure; Humans; Myocardial Infarction; Myocardial Reperfusion; Risk Assessment; Stroke Volume; Systole; Time Factors; Vascular Patency; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 23537961
DOI: 10.1016/j.ahj.2012.11.014