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ELife May 2024Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our...
Cardiac macrophages are heterogenous in phenotype and functions, which has been associated with differences in their ontogeny. Despite extensive research, our understanding of the precise role of different subsets of macrophages in ischemia/reperfusion (I/R) injury remains incomplete. We here investigated macrophage lineages and ablated tissue macrophages in homeostasis and after I/R injury in a CSF1R-dependent manner. Genomic deletion of a fms-intronic regulatory element (FIRE) in the locus resulted in specific absence of resident homeostatic and antigen-presenting macrophages, without affecting the recruitment of monocyte-derived macrophages to the infarcted heart. Specific absence of homeostatic, monocyte-independent macrophages altered the immune cell crosstalk in response to injury and induced proinflammatory neutrophil polarization, resulting in impaired cardiac remodeling without influencing infarct size. In contrast, continuous CSF1R inhibition led to depletion of both resident and recruited macrophage populations. This augmented adverse remodeling after I/R and led to an increased infarct size and deterioration of cardiac function. In summary, resident macrophages orchestrate inflammatory responses improving cardiac remodeling, while recruited macrophages determine infarct size after I/R injury. These findings attribute distinct beneficial effects to different macrophage populations in the context of myocardial infarction.
Topics: Animals; Macrophages; Mice; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Myocardial Ischemia; Myocardial Infarction; Male; Myocardial Reperfusion Injury; Mice, Inbred C57BL; Myocardium; Disease Models, Animal
PubMed: 38775664
DOI: 10.7554/eLife.89377 -
Iranian Biomedical Journal Mar 2024Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary... (Review)
Review
Despite the unconditional success achieved in the treatment and prevention of AMI over the past 40 years, mortality in this disease remains high. Hence, it is necessary to develop novel drugs with mechanism of action different from those currently used in clinical practices. Studying the molecular mechanisms involved in the cardioprotective effect of adapting to cold could contribute to the development of drugs that increase cardiac tolerance to the impact of ischemia/reperfusion. An analysis of the published data shows that the long-term human stay in the Far North contributes to the occurrence of cardiovascular diseases. At the same time, chronic and continuous exposure to cold increases tolerance of the rat heart to ischemia/ reperfusion. It has been demonstrated that the cardioprotective effect of cold adaptation depends on the activation of ROS production, stimulation of the β2-adrenergic receptor and protein kinase C, MPT pore closing, and KATP channel.
Topics: Humans; Animals; Cold Temperature; Adaptation, Physiological; Cardiovascular System; Myocardial Reperfusion Injury; Reperfusion Injury; Reactive Oxygen Species
PubMed: 38770843
DOI: 10.61186/ibj.3872 -
Journal of Vascular Surgery May 2024Hypertension (HTN) has been implicated as a strong predictive factor for poorer outcomes in patients undergoing various vascular procedures. However, limited research is...
BACKGROUND
Hypertension (HTN) has been implicated as a strong predictive factor for poorer outcomes in patients undergoing various vascular procedures. However, limited research is available that examines the effect of uncontrolled HTN (uHTN) on outcomes after carotid revascularization. We aimed to determine which carotid revascularization procedure yields the best outcome in this patient population.
METHODS
We studied patients undergoing carotid endarterectomy (CEA), transfemoral carotid artery stenting (TFCAS), or transcarotid artery revascularization (TCAR) from April 2020 to June 2022 using data from the Vascular Quality Initiative. Patients were stratified into two groups: those with cHTN and those with uHTN. Patients with cHTN were those with HTN treated with medication and a blood pressure of <130/80 mm Hg. Patients with uHTN had a blood pressure of ≥130/80 mm Hg. Our primary outcomes were in-hospital stroke, death, myocardial infarction (MI), and 30-day mortality. Our secondary outcomes were postoperative hypotension or HTN, reperfusion syndrome, prolonged length of stay (LOS) (>1 day), stroke/death, and stroke/death/MI. We used logistic regression models for the multivariate analysis.
RESULTS
A total of 34,653 CEA (uHTN, 11,347 [32.7%]), 8199 TFCAS (uHTN, 2307 [28.1%]), and 17,309 TCAR (uHTN, 4990 [28.8%]) patients were included in this study. There was no significant difference in age between patients with cHTN and patients with uHTN for each carotid revascularization procedure. However, compared with patients with cHTN, patients with uHTN had significantly more comorbidities. uHTN was associated with an increased risk of combined in-hospital stroke/death/MI after CEA (adjusted odds ratio [aOR], 1.56; 95% confidence interval [CI], 1.30-1.87; P < .001), TFCAS (aOR, 1.59; 95% CI, 1.21-2.08; P < .001), and TCAR (aOR, 1.39; 95% CI, 1.12-1.73; P = .003) compared with cHTN. Additionally, uHTN was associated with a prolonged LOS after all carotid revascularization methods. For the subanalysis of patients with uHTN, TFCAS was associated with an increased risk of stroke (aOR, 1.82; 95% CI, 1.39-2.37; P < .001), in-hospital death (aOR, 3.73; 95% CI, 2.25-6.19; P < .001), reperfusion syndrome (aOR, 6.24; 95% CI, 3.57-10.93; P < .001), and extended LOS (aOR, 1.87; 95% CI, 1.51-2.32; P < .001) compared with CEA. There was no statistically significant difference between the outcomes of TCAR compared with CEA.
CONCLUSIONS
The results from this study show that patients with uHTN are at a higher risk of stroke and death postoperatively compared with patients with cHTN, highlighting the importance of treating HTN before undergoing elective carotid revascularization. Additionally, in patients with uHTN, TFCAS yields the worst outcomes, whereas CEA and TCAR proved to be safer interventions. Patients with uTHN with symptomatic carotid disease treated with CEA or TCAR have better outcomes compared with those treated with TFCAS.
PubMed: 38763456
DOI: 10.1016/j.jvs.2024.05.021 -
Pharmacology & Therapeutics Jul 2024Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is... (Review)
Review
Acute myocardial infarction (AMI) remains a leading cause of death worldwide. Increased formation of reactive oxygen species (ROS) during the early reperfusion phase is thought to trigger lipid peroxidation and disrupt redox homeostasis, leading to myocardial injury. Whilst the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) is chiefly recognised for its central role in ethanol metabolism, substantial experimental evidence suggests an additional cardioprotective role for ALDH2 independent of alcohol intake, which mitigates myocardial injury by detoxifying breakdown products of lipid peroxidation including the reactive aldehydes, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Epidemiological evidence suggests that an ALDH2 mutant variant with reduced activity that is highly prevalent in the East Asian population increases AMI risk. Additional studies have uncovered a strong association between coronary heart disease and this ALDH2 mutant variant. It appears this enzyme polymorphism (in particular, in ALDH2*2/2 carriers) has the potential to have wide-ranging effects on thiol reactivity, redox tone and therefore numerous redox-related signaling processes, resilience of the heart to cope with lifestyle-related and environmental stressors, and the ability of the whole body to achieve redox balance. In this review, we summarize the journey of ALDH2 from a mitochondrial reductase linked to alcohol metabolism, via pre-clinical studies aimed at stimulating ALDH2 activity to reduce myocardial injury to clinical evidence for its protective role in the heart.
Topics: Humans; Aldehyde Dehydrogenase, Mitochondrial; Oxidation-Reduction; Myocardial Infarction; Animals; Ethanol; Polymorphism, Genetic; Aldehyde Dehydrogenase; Reactive Oxygen Species
PubMed: 38763322
DOI: 10.1016/j.pharmthera.2024.108666 -
The Journal of Biological Chemistry Jun 2024OMT-28 is a metabolically robust small molecule developed to mimic the structure and function of omega-3 epoxyeicosanoids. However, it remained unknown to what extent...
OMT-28 is a metabolically robust small molecule developed to mimic the structure and function of omega-3 epoxyeicosanoids. However, it remained unknown to what extent OMT-28 also shares the cardioprotective and anti-inflammatory properties of its natural counterparts. To address this question, we analyzed the ability of OMT-28 to ameliorate hypoxia/reoxygenation (HR)-injury and lipopolysaccharide (LPS)-induced endotoxemia in cultured cardiomyocytes. Moreover, we investigated the potential of OMT-28 to limit functional damage and inflammasome activation in isolated perfused mouse hearts subjected to ischemia/reperfusion (IR) injury. In the HR model, OMT-28 (1 μM) treatment largely preserved cell viability (about 75 versus 40% with the vehicle) and mitochondrial function as indicated by the maintenance of NAD+/NADH-, ADP/ATP-, and respiratory control ratios. Moreover, OMT-28 blocked the HR-induced production of mitochondrial reactive oxygen species. Pharmacological inhibition experiments suggested that Gαi, PI3K, PPARα, and Sirt1 are essential components of the OMT-28-mediated pro-survival pathway. Counteracting inflammatory injury of cardiomyocytes, OMT-28 (1 μM) reduced LPS-induced increases in TNFα protein (by about 85% versus vehicle) and NF-κB DNA binding (by about 70% versus vehicle). In the ex vivo model, OMT-28 improved post-IR myocardial function recovery to reach about 40% of the baseline value compared to less than 20% with the vehicle. Furthermore, OMT-28 (1 μM) limited IR-induced NLRP3 inflammasome activation similarly to a direct NLRP3 inhibitor (MCC950). Overall, this study demonstrates that OMT-28 possesses potent cardio-protective and anti-inflammatory properties supporting the hypothesis that extending the bioavailability of omega-3 epoxyeicosanoids may improve their prospects as therapeutic agents.
Topics: Animals; Mice; Myocytes, Cardiac; Cardiotonic Agents; Inflammasomes; Myocardial Reperfusion Injury; Lipopolysaccharides; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Mice, Inbred C57BL; Sirtuin 1; Anti-Inflammatory Agents; Reactive Oxygen Species; Fatty Acids, Omega-3; Endotoxemia
PubMed: 38754781
DOI: 10.1016/j.jbc.2024.107372 -
Gaceta Medica de Mexico 2024The prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and previous percutaneous coronary intervention (PCI) is uncertain. (Observational Study)
Observational Study Comparative Study
BACKGROUND
The prognosis of patients with ST-segment elevation myocardial infarction (STEMI) and previous percutaneous coronary intervention (PCI) is uncertain.
OBJECTIVE
To evaluate if previous PCI in patients with STEMI increases the risk of major cardiovascular events, and if final epicardial blood flow differs according to the reperfusion strategy.
MATERIAL AND METHODS
Observational, longitudinal, comparative sub-study of the PHASE-MX trial that included patients with STEMI and reperfusion within 12 hours of symptom onset, who were classified according to their history of PCI. The occurrence of the composite primary endpoint (cardiovascular death, re-infarction, congestive heart failure and cardiogenic shock) within 30 days was evaluated using Kaplan-Meier estimates, log-rank test and Cox proportional hazards model. Epicardial blood flow was assessed using the TIMI grading system after reperfusion.
RESULTS
A total of 935 patients were included; 85.6% were males and 6.9% had a history of PCI; 53% underwent pharmacoinvasive therapy, and 47%, primary PCI. The incidence of the composite primary endpoint at 30 days in patients with a history of PCI was 9.8% vs 13.3% in those with no previous PCI (p = 0.06). Among the patients with previous PCI, 87.1% reached a final TIMI grade 3 flow after primary PCI vs. 75% in the group with pharmacoinvasive strategy (p = 0.235).
CONCLUSIONS
A history of PCI does not increase the risk of major cardiovascular events at 30 days; however, it impacted negatively on the final angiographic blood flow of patients that received pharmacoinvasive therapy (compared to primary PCI).
Topics: Humans; Percutaneous Coronary Intervention; Male; Female; ST Elevation Myocardial Infarction; Middle Aged; Aged; Coronary Angiography; Longitudinal Studies; Treatment Outcome; Prognosis; Kaplan-Meier Estimate; Proportional Hazards Models
PubMed: 38753565
DOI: 10.24875/GMM.M24000847 -
The Eurasian Journal of Medicine Dec 2023This review assesses the efficacy of inhalation anesthetics and propofol in cardiac surgery, primarily focusing on their impact on myocardial protection and subsequent...
This review assesses the efficacy of inhalation anesthetics and propofol in cardiac surgery, primarily focusing on their impact on myocardial protection and subsequent clinical outcomes. The review provides a concise summary of the current scientific information regarding the protective efects of inhalation anesthetics and propofol, particularly in the context of ischemia-reperfusion injury during cardiac surgery. The review delves into the mechanisms of action and discusses clinical studies comparing the 2 anesthetic strategies regarding mortality, complication rates, and length of hospital stay. Inhalation anesthetics exhibit cardioprotective properties through many mechanisms, such as preconditioning, scavenging of free radicals, and stabilizing mitochondria. Propofol demonstrates certain protective benefits but does not possess the preconditioning capability of inhalation medications. Clinical investigations yield contradictory findings, as several studies indicate enhanced outcomes with inhalation anesthetics, while others observe no substantial disparity between the 2 approaches. The cardioprotective efcacy of propofol against ischemia-reperfusion injury remains limited. While its inherent antioxidant properties ofer direct myocardial protection, propofol demonstrably lacks the preconditioning-mediated signaling pathways triggered by inhalation anesthetics. As a result, propofol's protective efect may be slightly inferior to preconditioning strategies, and its potential to inhibit organ-protective impact of other interventions needs further investigation. The question of which anesthetic approach ofers superior myocardial protection remains debatable. Current evidence is inconclusive, potentially due to patient heterogeneity, surgical complexity, and methodological limitations of existing studies. Future research, including pharmacogenetic studies and large, welldesigned, randomized controlled trials, are necessary to provide definitive guidance on anesthetic selection for optimal myocardial protection in cardiac surgery.
PubMed: 38752865
DOI: 10.5152/eurasianjmed.2023.23376 -
ESC Heart Failure May 2024The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an...
AIMS
The Selvester scoring system has been derived from ECG parameters for estimating infarct size. However, there is still a lack of evidence for Selvester score as an alternative to cardiac magnetic resonance (CMR) myocardial injury makers for risk stratification and prediction of left ventricular function (LVF) recovery among patients with ST-segment elevation myocardial infarction (STEMI).
METHODS AND RESULTS
This multicentre observational study enrolled 328 STEMI patients (88.4% men, 57.3 ± 10.6 years of age) undergoing CMR examination 1 week post-reperfusion therapy. Patients with baseline left ventricular ejection fraction (LVEF) < 50% underwent a follow-up CMR 6 months later, categorized into baseline normal LVF (ejection fraction [EF] ≥ 50% at baseline, n = 155); recovered LVF (EF < 50% at baseline and ≥50% after 6 months, n = 69); and reduced LVF (EF < 50% at baseline and after 6 months, n = 104). The median follow-up was 4 (3-4) years for all patients, with 61 patients experiencing major adverse cardiovascular event (MACEs). Patients with reduced LVF had a higher risk of MACEs than those with baseline normal LVF (P = 0.01), while the recovered LVF group had no significant difference (P > 0.05). A Selvester score >10 doubled the risk of MACEs in patients with systolic dysfunction (1.91 [1.02 to 3.58], P = 0.04). Additionally, Selvester score, baseline LVEF, transmural infarction, and peak CK-MB were independent predictors of recovered LVF, with Selvester score providing incremental predictive value to peak CK-MB in predicting recovered LVF (∆AUC = 0.07, P < 0.05).
CONCLUSIONS
The Selvester score improves risk stratification among STEMI patients beyond LVEF and provide independent and incremental information to clinical parameters in predicting recovered LVF.
PubMed: 38751328
DOI: 10.1002/ehf2.14795 -
International Heart Journal May 2024The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been...
The effectiveness of ischemic postconditioning (iPoC) in patients with ST-elevation myocardial infarction (STEMI) without ischemic preconditioning has not been determined. Therefore, we investigated the impact of iPoC and its potential mechanism related to heat shock protein 72 (HSP72) induction on myocardial salvage in patients with STEMI without prodromal angina (PA).We retrospectively analyzed data from 102 patients with STEMI with successful reperfusion among 323 consecutive patients with acute coronary syndrome. Among these, 55 patients with iPoC (iPoC (+) ) underwent 4 cycles of 60-second inflation and 30-second deflation of the angioplasty balloon. Both the iPoC (+) and iPoC (-) groups were divided into 2 further subgroups: patients with PA (PA (+) ) and those without (PA (-) ). We analyzed HSP72 levels in neutrophils, which were measured until 48 hours after reperfusion. I-123 β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) scintigraphy was performed within a week of reperfusion therapy. In 64% of patients, thallium-201 (TL) scintigraphy was performed 6-8 months after STEMI onset.Using BMIPP and TL, in the PA (-) subgroups, the iPoC (+) group had a significantly greater myocardial salvage ratio than the iPoC (-) group. iPoC was identified as an independent predictor of the myocardial salvage ratio. The HSP72 increase ratio was significantly elevated in the iPoC (+) PA (-) group. Importantly, the myocardial salvage effect in patients without PA was significantly correlated with the HSP72 increase ratio, which was greater in patients with iPoC.These results suggest the potential impact of iPoC via HSP72 induction on myocardial salvage; however, the effects may be limited to patients with STEMI without PA.
Topics: Humans; Male; Female; HSP72 Heat-Shock Proteins; Retrospective Studies; Aged; Middle Aged; ST Elevation Myocardial Infarction; Ischemic Postconditioning; Angina Pectoris; Prodromal Symptoms; Percutaneous Coronary Intervention; Neutrophils
PubMed: 38749746
DOI: 10.1536/ihj.23-651 -
Arquivos Brasileiros de Cardiologia 2024Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction...
BACKGROUND
Early reperfusion therapy is acknowledged as the most effective approach for reducing case fatality rates in patients with ST-segment elevation myocardial infarction (STEMI).
OBJECTIVE
Estimate the clinical and economic consequences of delaying reperfusion in patients with STEMI.
METHODS
This retrospective cohort study evaluated mortality rates and the total expenses incurred by delaying reperfusion therapy among 2622 individuals with STEMI. Costs of in-hospital care and lost productivity due to death or disability were estimated from the perspective of the Brazilian Unified Health System indexed in international dollars (Int$) adjusted by purchase power parity. A p < 0.05 was considered statistically significant.
RESULTS
Each additional hour of delay in reperfusion therapy was associated with a 6.2% increase (95% CI: 0.3% to 11.8%, p = 0.032) in the risk of in-hospital mortality. The overall expenses were 45% higher among individuals who received treatment after 9 hours compared to those who were treated within the first 3 hours, primarily driven by in-hospital costs (p = 0.005). A multivariate linear regression model indicated that for every 3-hour delay in thrombolysis, there was an increase in in-hospital costs of Int$497 ± 286 (p = 0.003).
CONCLUSIONS
The findings of our study offer further evidence that emphasizes the crucial role of prompt reperfusion therapy in saving lives and preserving public health resources. These results underscore the urgent need for implementing a network to manage STEMI cases.
Topics: Humans; Female; Male; Retrospective Studies; ST Elevation Myocardial Infarction; Middle Aged; Time Factors; Brazil; Hospital Mortality; Aged; Time-to-Treatment; Myocardial Reperfusion; Treatment Outcome; Hospital Costs; Thrombolytic Therapy
PubMed: 38747748
DOI: 10.36660/abc.20230650