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Journal of Cardiothoracic Surgery Jun 2024Primary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the... (Review)
Review
Primary graft dysfunction (PGD) is a life-threatening clinical condition with a high mortality rate, presenting as left, right, or biventricular dysfunction within the initial 24 h following heart transplantation, in the absence of a discernible secondary cause. Given its intricate nature, definitive definition and diagnosis of PGD continues to pose a challenge. The pathophysiology of PGD encompasses numerous underlying mechanisms, some of which remain to be elucidated, including factors like myocardial damage, the release of proinflammatory mediators, and the occurrence of ischemia-reperfusion injury. The dynamic characteristics of both donors and recipients, coupled with the inclination towards marginal lists containing more risk factors, together contribute to the increased incidence of PGD. The augmentation of therapeutic strategies involving mechanical circulatory support accelerates myocardial recovery, thereby significantly contributing to survival. Nonetheless, a universally accepted treatment algorithm for the swift management of this clinical condition, which necessitates immediate intervention upon diagnosis, remains absent. This paper aims to review the existing literature and shed light on how diagnosis, pathophysiology, risk factors, treatment, and perioperative management affect the outcome of PGD.
Topics: Humans; Heart Transplantation; Primary Graft Dysfunction; Risk Factors
PubMed: 38824545
DOI: 10.1186/s13019-024-02816-6 -
BMC Cardiovascular Disorders May 2024Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane...
BACKGROUND
Myocardial ischemia-reperfusion injury (I/RI) is a major cause of perioperative cardiac-related adverse events and death. Studies have shown that sevoflurane postconditioning (SpostC), which attenuates I/R injury and exerts cardioprotective effects, regulates mitochondrial dynamic balance via HIF-1α, but the exact mechanism is unknown. This study investigates whether the PI3K/AKT pathway in SpostC regulates mitochondrial dynamic balance by mediating HIF-1α, thereby exerting myocardial protective effects.
METHODS
The H9C2 cardiomyocytes were cultured to establish the hypoxia-reoxygenation (H/R) model and randomly divided into 4 groups: Control group, H/R group, sevoflurane postconditioning (H/R + SpostC) group and PI3K/AKT blocker (H/R + SpostC + LY) group. Cell survival rate was determined by CCK-8; Apoptosis rate was determined by flow cytometry; mitochondrial membrane potential was evaluated by Mito Tracker™ Red; mRNA expression levels of AKT, HIF-1α, Opa1and Drp1 were detected by quantitative real-time polymerase chain reaction (qRT-PCR); Western Blot assay was used to detect the protein expression levels of AKT, phosphorylated AKT (p-AKT), HIF-1α, Opa1 and Drp1.
RESULTS
Compared with the H/R group, the survival rate of cardiomyocytes in the H/R + SpostC group increased, the apoptosis rate decreased and the mitochondrial membrane potential increased. qRT-PCR showed that the mRNA expression of HIF-1α and Opa1 were higher in the H/R + SpostC group compared with the H/R group, whereas the transcription level of Drp1 was lower in the H/R + SpostC group. In the H/R + SpostC + LY group, the mRNA expression of HIF-1α was lower than the H/R + SpostC group. There was no difference in the expression of Opa1 mRNA between the H/R group and the H/R + SpostC + LY group. WB assay results showed that compared with the H/R group, the protein expression levels of HIF-1α, Opa1, P-AKT were increased and Drp1 protein expression levels were decreased in the H/R + SpostC group. HIF-1α, P-AKT protein expression levels were decreased in the H/R + SpostC + LY group compared to the H/R + SpostC group.
CONCLUSION
SpostC mediates HIF-1α-regulated mitochondrial fission and fusion-related protein expression to maintain mitochondrial dynamic balance by activating the PI3K/AKT pathway and increasing AKT phosphorylation, thereby attenuating myocardial I/R injury.
Topics: Hypoxia-Inducible Factor 1, alpha Subunit; Proto-Oncogene Proteins c-akt; Animals; Myocytes, Cardiac; Sevoflurane; Signal Transduction; Myocardial Reperfusion Injury; Mitochondrial Dynamics; Cell Line; Rats; Apoptosis; Phosphatidylinositol 3-Kinase; Mitochondria, Heart; Membrane Potential, Mitochondrial; Cell Hypoxia; Dynamins; GTP Phosphohydrolases; Phosphoinositide-3 Kinase Inhibitors; Cytoprotection; Ischemic Postconditioning; Phosphorylation
PubMed: 38811893
DOI: 10.1186/s12872-024-03868-1 -
Biomedicine & Pharmacotherapy =... Jul 2024Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the... (Review)
Review
Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy.
Topics: Myocardial Reperfusion Injury; Humans; Animals; Hormones; Cardiotonic Agents
PubMed: 38805965
DOI: 10.1016/j.biopha.2024.116764 -
Texas Heart Institute Journal May 2024Left main occlusion presenting as ST-segment elevation myocardial infarction is an exceedingly morbid condition. This article reports a case of cardiac arrest in a...
Left main occlusion presenting as ST-segment elevation myocardial infarction is an exceedingly morbid condition. This article reports a case of cardiac arrest in a patient after a treadmill stress test. Coronary angiography revealed 100% occlusion of the left main coronary artery. Left ventricular unloading with the Impella CP heart pump (ABIOMED/Johnson & Johnson MedTech) was used, after which epicardial blood flow was restored without angioplasty. The patient underwent surgical revascularization. Despite a prolonged revascularization time, there was no evidence of severe myocardial injury postoperatively.
Topics: Humans; Middle Aged; Coronary Angiography; Coronary Circulation; Coronary Occlusion; Electrocardiography; Heart-Assist Devices; Myocardial Revascularization; Pericardium; Prosthesis Design; Recovery of Function; ST Elevation Myocardial Infarction; Treatment Outcome; Ventricular Function, Left; Female
PubMed: 38805372
DOI: 10.14503/THIJ-23-8322 -
Frontiers in Bioengineering and... 2024Prompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional...
INTRODUCTION
Prompt reperfusion of coronary artery after acute myocardial infarction (AMI) is crucial for minimizing heart injury. The myocardium, however, may experience additional injury due to the flow restoration itself (reperfusion injury, RI). The purpose of this study was to demonstrate that short preconditioning (10 min) with selective autoretroperfusion (SARP) ameliorates RI, based on a washout hypothesis.
METHODS
AMI was induced in 23 pigs (3 groups) by occluding the left anterior descending (LAD) artery. In SARP-b (SARP balloon inflated) and SARP-nb (SARP balloon deflated) groups, arterial blood was retroperfused for 10 min via the great cardiac vein before releasing the arterial occlusion. A mathematical model of coronary circulation was used to simulate the SARP process and evaluate the potential washout effect.
RESULTS
SARP restored left ventricular function during LAD occlusion. Ejection fraction in the SARP-b group returned to baseline levels, compared to SARP-nb and control groups. Infarct area was significantly larger in the control group than in the SARP-b and SARP-nb groups. End-systolic wall thickness was preserved in the SARP-b compared to the SARP-nb and control groups. Analyte values (pH, lactate, glucose, and others), measured every 2 min during retroperfusion, suggest a "washout" effect as one important mechanism of action of SARP in reducing infarct size. With SARP, the values progressively approached baseline levels. The mathematical model also confirmed a possible washout effect of tracers.
DISCUSSION
RI can be ameliorated by delaying restoration of arterial flow for a brief period of time while pretreating the infarction with SARP to restore homeostasis via a washout mechanism.
PubMed: 38798957
DOI: 10.3389/fbioe.2024.1386713 -
Experimental Animals May 2024Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2...
Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs and is often associated with severe cellular damage and death. Ectodysplasin-A2 receptor (EDA2R) is a member of the TNF receptor family that has anti-inflammatory and antioxidant effects. However, to the best of our knowledge, its role in the progression of myocardial I/R injury remains unclear. The present study aimed to investigate the role of EDA2R during myocardial I/R injury and the molecular mechanisms involved. In vitro, dexmedetomidine (DEX) exhibited a protective effect on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury and downregulated EDA2R expression. Subsequently, EDA2R silencing enhanced cell viability and reduced the apoptosis of cardiomyocytes. Furthermore, knockdown of EDA2R led to an elevated mitochondrial membrane potential (MMP), repressed the release of Cytochrome C and upregulated Bcl-2 expression. EDA2R knockdown also resulted in downregulated expression of Bax, and decreased activity of Caspase-3 and Caspase-9 in cardiomyocytes, reversing the effects of H/R on mitochondria-mediated apoptosis. In addition, knockdown of EDA2R suppressed H/R-induced oxidative stress. Mechanistically, EDA2R knockdown inactivated the NF-κB signaling pathway. Additionally, downregulation of EDA2R weakened myocardial I/R injury in mice, as reflected by improved left ventricular function and reduced infarct size, as well as suppressed apoptosis and oxidative stress. Additionally, EDA2R knockdown repressed the activation of NF-κB signal in vivo. Collectively, knockdown of EDA2R exerted anti-apoptotic and antioxidant effects against I/R injury in vivo and in vitro by suppressing the NF-κB signaling pathway.
PubMed: 38797667
DOI: 10.1538/expanim.24-0020 -
Journal of Translational Medicine May 2024Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases....
BACKGROUND
Myocardial ischemia-reperfusion injury (MIRI) is caused by reperfusion after ischemic heart disease. LncRNA Snhg1 regulates the progression of various diseases. N6-methyladenosine (mA) is the frequent RNA modification and plays a critical role in MIRI. However, it is unclear whether lncRNA Snhg1 regulates MIRI progression and whether the lncRNA Snhg1 was modified by mA methylation.
METHODS
Mouse cardiomyocytes HL-1 cells were utilized to construct the hypoxia/reoxygenation (H/R) injury model. HL-1 cell viability was evaluated utilizing CCK-8 method. Cell apoptosis, mitochondrial reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were quantitated utilizing flow cytometry. RNA immunoprecipitation and dual-luciferase reporter assays were applied to measure the mA methylation and the interactions between lncRNA Snhg1 and targeted miRNA or target miRNAs and its target gene. The I/R mouse model was constructed with adenovirus expressing lncRNA Snhg1. HE and TUNEL staining were used to evaluate myocardial tissue damage and apoptosis.
RESULTS
LncRNA Snhg1 was down-regulated after H/R injury, and overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization. Besides, lncRNA Snhg1 could target miR-361-5p, and miR-361-5p targeted OPA1. Overexpressed lncRNA Snhg1 suppressed H/R-stimulated cell apoptosis, mitochondrial ROS level and polarization though the miR-361-5p/OPA1 axis. Furthermore, WTAP induced lncRNA Snhg1 mA modification in H/R-stimulated HL-1 cells. Moreover, enforced lncRNA Snhg1 repressed I/R-stimulated myocardial tissue damage and apoptosis and regulated the miR-361-5p and OPA1 levels.
CONCLUSION
WTAP-mediated mA modification of lncRNA Snhg1 regulated MIRI progression through modulating myocardial apoptosis, mitochondrial ROS production, and mitochondrial polarization via miR-361-5p/OPA1 axis, providing the evidence for lncRNA as the prospective target for alleviating MIRI progression.
Topics: Animals; RNA, Long Noncoding; MicroRNAs; Myocardial Reperfusion Injury; Mice; Apoptosis; Mitochondrial Dynamics; Myocytes, Cardiac; Cell Line; Male; Mice, Inbred C57BL; GTP Phosphohydrolases; Reactive Oxygen Species; Adenosine; Base Sequence; Methylation; Membrane Potential, Mitochondrial
PubMed: 38796415
DOI: 10.1186/s12967-024-05330-4 -
Redox Biology Jul 2024Exploring and discovering novel circRNAs is one of the ways to develop innovative drugs for the diagnosis and treatment of myocardial ischemia-reperfusion injury...
Exploring and discovering novel circRNAs is one of the ways to develop innovative drugs for the diagnosis and treatment of myocardial ischemia-reperfusion injury (MI/RI). In the work, some dysregulated circRNAs were found by microarray screening analysis in AC16 cells, and hsa_circRNA_104852 named circMIRIAF was screened, which was up-regulated in AC16 cells damaged by hypoxia-reoxygenation injury (H/RI). The comprehensive analysis of ceRNA network revealed the potential relationship of circMIRIAF/miR-544/WDR12. Then, the results of interaction research confirmed that circMIRIAF acted as sponge of miR-544 to positively regulate WDR12 protein expression. Further, the validation results indicate that miR-544 silencing increased the expression of WDR12, and WDR12 activated Notch1 signal to aggravate H/RI of AC16 cells and MI/RI of mice via regulating oxidative stress and inflammation. Furthermore, silencing circMIRIAF caused the decreased circMIRIAF levels and the increased miR-544 levels in cardiomyocytes, while excessive miR-544 inhibited WDR12 expression to alleviate the disorder. On the contrary, excessive circMIRIAF increased WDR12 expression by adsorbing miR-544 to exacerbate H/RI in AC16 cells. In addition, circMIRIAF siRNA reversed the aggravation of H/RI in cells caused by WDR12 overexpression. Overall, circMIRIAF can serve as a drug target or treating MI/RI, and circMIRIAF could sponge miR-544 and enhance WDR12 expression to aggravate MI/RI, which may provide a novel therapeutic strategy for MI/RI treatment.
Topics: Animals; Humans; Male; Mice; Cell Line; Disease Models, Animal; Gene Expression Regulation; MicroRNAs; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress; RNA, Circular; Signal Transduction
PubMed: 38795544
DOI: 10.1016/j.redox.2024.103175 -
International Journal of Molecular... May 2024Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction... (Review)
Review
Initial Despair and Current Hope of Identifying a Clinically Useful Treatment of Myocardial Reperfusion Injury: Insights Derived from Studies of Platelet P2Y Antagonists and Interference with Inflammation and NLRP3 Assembly.
Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.
Topics: Myocardial Reperfusion Injury; Humans; Purinergic P2Y Receptor Antagonists; Animals; NLR Family, Pyrin Domain-Containing 3 Protein; Inflammation; Receptors, Purinergic P2Y12
PubMed: 38791515
DOI: 10.3390/ijms25105477 -
Biomedicines May 2024Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion...
Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion (I/R) injury, leading to cardiac damage and dysfunction. Platelets are major players in hemostasis and play a crucial role in vessel occlusion, inflammation, and cardiac remodeling after I/R. Here, we studied the impact of platelets on cell apoptosis in the myocardium using a close-chest mouse model of AMI. We found caspase-3-positive resident cardiac cells, while leukocytes were negative for caspase-3. Using two different mouse models of thrombocytopenia, we detected a significant reduction in caspase-3 positive cells in the infarct border zone after I/R injury. Further, we identified platelet FasL to induce cell apoptosis via the extrinsic pathway of Fas receptor activation of target cells. Mechanistically, hypoxia triggers platelet adhesion to FasR, suggesting that platelet-induced apoptosis is elevated after I/R. Platelet-specific FasL knock-out mice showed reduced and expression, suggesting that platelets modulate the intrinsic and extrinsic pathways of apoptosis, leading to reduced infarct size after myocardial I/R injury. Thus, a new mechanism for how platelets contribute to tissue homeostasis after AMI was identified that should be validated in patients soon.
PubMed: 38791039
DOI: 10.3390/biomedicines12051077