Acute Cardiac Dysfunction Research Articles

Integrative omics analysis identifies biomarkers of septic cardiomyopathy.

Septic Cardiomyopathy (SCM) is a syndrome of acute cardiac dysfunction in septic patients, unrelated to cardiac ischemia. Multiomics studies including transcriptomics and proteomics have provided new insights into the mechanisms of SCM. In here, a rat model of SCM was established by intraperitoneal injection of lipopolysaccharide (LPS). Biomarkers of SCM were characterized via a multi-omics analysis. The differentially expressed (DE) mRNAs predominantly appeared in pathways linked to the immune response, inflammatory response, and the complement and coagulation cascades, while DE proteins were mainly enriched in pathways associated with the complement and coagulation cascades. On this basis, the integrated analysis was performed between transcriptome and proteome. The potential biomarkers were further verified by RT-qPCR and WB. The current proteotranscriptomic research has furnished a valuable dataset and fresh perspectives that will enhance our comprehension of the development of SCM. This, in turn, is expected to expedite the formulation of novel approaches for the prevention and management of SCM in patients.

Hydrogel encapsulating gold nanoparticles for targeted delivery of nitroglycerin to reduce post-cardiac dysfunction inflammation by inhibiting the Wnt/β-catenin signaling pathway.

The discovery of nitric oxide's role in biological processes like platelet function, vasodilation, cell permeability, and inflammation has advanced our understanding of organic nitrate therapy's hemodynamic and nonhemodynamic effects. Short-term use of organic nitrates prevents left ventricular enlargement and infarct expansion. However, information on their long-term impact on LV remodeling in post-acute cardiac dysfunction patients is limited. In this study, we utilized an innovative active hydrogel with gelatin (Gel)/polyethylene glycol (PEG)/polylactic acid (PLA) encapsulating gold nanoparticles (AuNPs)-based drug delivery system for the sustained release of nitroglycerin (NTG). Gel/PEG/PLA/NTG/AuNPs hydrogel-based system is a non-transplant surgical method that can adhere to the surface of the heart and deliver the drug directly to the epicardium. Cardiac dysfunction was induced by ligating the left anterior descending coronary artery. Echocardiograms were used to study the pre- and post-operative hemodynamics. Hematoxylin and eosin (H&E) and Masson's trichrome stain (MTS) stainingrevealed that the acute myocardial infarction (AMI) rats' group had irregularly shaped fibers and a lack of transverse striations, whereas Gel/PEG/PLA/NTG/AuNPs hydrogel group showed significant improvement. Rats in the Gel/PEG/PLA hydrogel group demonstrated marked vasodilation, compared to the AMI group. Mechanistically, we determined that hydrogel disrupts the initiation of post-cardiac dysfunction via inhibiting Wnt/β-catenin transcriptional activation. Hence, the Gel/PEG/PLA/NTG/AuNPs hydrogel group effectively protected against ischemic injury and inflammation in AMI, demonstrating a novel method for treating acute cardiac dysfunction.

The role of TREM-1 in septic myocardial pyroptosis and septic cardiomyopathy in vitro and in vivo.

Septic cardiomyopathy (SCM) is an acute cardiac dysfunction involving myocardial cell pyroptosis. TREM-1 is a known receptor on cell membrane that can amplify the inflammatory response. Our previous studies have shown that TREM-1 in cardiomyocytes is involved in the activation of NLRP3 through the SMC4/NEMO pathway. Here, we aimed to use Trem-1 and Nlrp3 knockout mice to verify the effect of TREM-1 through NLRP3 on cardiac function in septic mice. The results showed that TREM-1 knockout resulted in a decrease in the release of downstream cell signals, including SMC4 and NLRP3, resulting in a decrease in cytokine release and improvement of cardiac dysfunction. Knockout of NLRP3 also reduced cardiomyocyte pyroptosis and increased survival rate. The therapeutic targeting of TREM-1 activation of NLRP3 and its pathway may contribute to the treatment or prevention of SCM.

Microparticle Mediated Delivery of Apelin Improves Heart Function in Post Myocardial Infarction Mice.

Apelin is an endogenous prepropeptide that regulates cardiac homeostasis and various physiological processes. Intravenous injection has been shown to improve cardiac contractility in patients with heart failure. However, its short half-life prevents studying its impact on left ventricular remodeling in the long term. Here, we aim to study whether microparticle-mediated slow release of apelin improves heart function and left ventricular remodeling in mice with myocardial infarction (MI). A cardiac patch was fabricated by embedding apelin-containing microparticles in a fibrin gel scaffold. MI was induced via permanent ligation of the left anterior descending coronary artery in adult C57BL/6J mice followed by epicardial patch placement immediately after (acute MI) or 28 days (chronic MI) post-MI. Four groups were included in this study, namely sham, MI, MI plus empty microparticle-embedded patch treatment, and MI plus apelin-containing microparticle-embedded patch treatment. Cardiac function was assessed by transthoracic echocardiography. Cardiomyocyte morphology, apoptosis, and cardiac fibrosis were evaluated by histology. Cardioprotective pathways were determined by RNA sequencing, quantitative polymerase chain reaction, and Western blot. The level of endogenous apelin was largely reduced in the first 7 days after MI induction and it was normalized by day 28. Apelin-13 encapsulated in poly(lactic-co-glycolic acid) microparticles displayed a sustained release pattern for up to 28 days. Treatment with apelin-containing microparticle-embedded patch inhibited cardiac hypertrophy and reduced scar size in both acute and chronic MI models, which is associated with improved cardiac function. Data from cellular and molecular analyses showed that apelin inhibits the activation and proliferation of cardiac fibroblasts by preventing transforming growth factor-β-mediated activation of Smad2/3 (supporessor of mothers against decapentaplegic 2/3) and downstream profibrotic gene expression. Poly(lactic-co-glycolic acid) microparticles prolonged the apelin release time in the mouse hearts. Epicardial delivery of the apelin-containing microparticle-embedded patch protects mice from both acute and chronic MI-induced cardiac dysfunction, inhibits cardiac fibrosis, and improves left ventricular remodeling.

Exceptionally rare MINOCA: a case of acute myocardial infarction following surgery for Stanford type A aortic dissection

BackgroundAortic dissection is a severe cardiovascular condition associated with high mortality rates, particularly in cases of Stanford type A aortic dissection (TAAD). Myocardial infarction with non-obstructive coronary arteries (MINOCA) following surgery for TAAD is rare but potentially fatal.Case presentation: A 69-year-old woman presented with sudden chest pain and was diagnosed with acute TAAD. Emergency surgery was performed, during which complications arose, including significant hemodynamic instability. Despite efforts to manage the patient’s condition postoperatively, she developed hemodynamic instability and myocardial infarction, leading to cardiogenic shock. MINOCA was diagnosed based on clinical presentation, echocardiographic findings, and coronary angiography ruling out significant stenosis or occlusion. The patient’s condition deteriorated despite aggressive treatment, ultimately resulting in death.ConclusionMINOCA following surgery for TAAD is a rare but serious complication. Vigilant postoperative monitoring and timely intervention are essential for identifying and managing acute cardiac dysfunction in these patients. Further research is required to improve outcomes in this challenging clinical scenario.

Research progress on the relationship between the gut microbiota dysbiosis and sepsis-induced cardiomyopathy

Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection. Sepsis-induced cardiomyopathy (SICM), as a serious complication of sepsis, is an acute reversible cardiac dysfunction syndrome unrelated to myocardial ischemia, which affects the outcome and prognosis of sepsis. As a complex microbial system, gut microbiota has been confirmed to be involved in the development of coronary heart disease, hypertension, heart failure and other cardiovascular diseases, and is also related to the occurrence and development of sepsis. However, there are few studies on the relationship between gut microbiota and SICM. This paper reviews the current research progress on gut microbiota and SICM, aiming at provide a new idea for clinical treatment of SICM.

Understanding the pathobiology of intermediate filaments to curb acute and chronic cardiac dysfunction

Understanding the pathobiology of intermediate filaments to curb acute and chronic cardiac dysfunction

Takotsubo's Cardiomyopathy in a Young Female with Severe Traumatic Brain Injury: A Case Report

AbstractTakotsubo's cardiomyopathy (TC) typically presents with acute cardiac dysfunction due to regional wall motion abnormality, but unlike other cardiac pathologies, it recovers within a short period. Here, we report the case of a 23-year-old woman who presented to us following severe traumatic brain injury (TBI). Her Glasgow coma scale (GCS) deteriorated rapidly in the preoperative period and she developed TC following surgery. Despite an uneventful surgery, she needed cardiovascular support by vasopressors and inotropes in the postoperative period. She was diagnosed with TC on serial transthoracic echocardiography, with complete cardiac function recovery within 9 days. The diagnosis of TC was supported by electrocardiography (not correlating coronary artery disease), elevated troponin I and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and the presence of a physical sessor like TBI. As an unrecognized TC due to a low GCS score after severe TBI may negatively impact outcomes, we aim to emphasize that vigilant perioperative management may give good outcomes even in less commonly encountered serious TC.

Clinical implications of septic cardiomyopathy: A narrative review.

Sepsis is caused by the body's dysregulated response to infection, which can lead to multiorgan injury and death. Patients with sepsis may develop acute cardiac dysfunction, termed septic cardiomyopathy, which is a global but reversible dysfunction of both sides of the heart. This narrative review discusses the mechanistic changes in the heart during septic cardiomyopathy, its diagnosis, existing treatment options regarding severity and course, and emerging treatment approaches. Although no standardized definition for septic cardiomyopathy exists, it is described as a reversible myocardial dysfunction that typically resolves within 7 to 10 days. Septic cardiomyopathy is often diagnosed based on electrocardiography, cardiac magnetic resonance imaging, biomarkers, and direct invasive and noninvasive measures of cardiac output. Presently, the treatment of septic cardiomyopathy is similar to that of sepsis, primarily focusing on acute interventions. Treatments for cardiomyopathy often include angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics. However, because of profound hypotension in sepsis, many cardiomyopathy treatments are contraindicated in patients with septic cardiomyopathy. Substantial efforts have been made to study the pathophysiological mechanisms and diagnostic options; however, the lack of a uniform definition for septic cardiomyopathy is challenging for physicians when considering treatments. Another challenge for physicians is that the treatment for septic cardiomyopathy has only focused on acute intervention, whereas the treatment for other cardiomyopathies has been provided on a long-term basis. A better understanding of the underlying mechanisms of septic cardiomyopathy may contribute to the development of a unified definition of the condition and novel treatment options.

Long-term global longitudinal strain abnormalities in paediatric patients after multisystem inflammatory syndrome in children correlate with cardiac troponin T: a single-centre cohort study.

Multisystem inflammatory syndrome in children is an inflammatory syndrome related to severe acute respiratory syndrome coronavirus 2 with a high risk of cardiovascular complications (vasoplegia, cardiac shock). We investigated the cardiac outcomes in multisystem inflammatory syndrome in children, focusing on the identification of predictors for late cardiac function impairment. Clinical characteristics, conventional echocardiography (left ventricle ejection fraction, fractional shortening), 4-chamber left ventricular global longitudinal strain, and cardiac MRI of multisystem inflammatory syndrome in children patients (n = 48) were collected during admission, 6 weeks, 6 months, >12-≤18 months, and >18-≤24 months post-onset. Paired over-time patterns were assessed and multivariable regression analyses were performed to identify predictors for late global longitudinal strain impairment. In total, 81.3% of patients had acute cardiac dysfunction (left ventricle ejection fraction <50% and/or fractional shortening <28%). The left ventricle ejection fraction and fractional shortening reached a plateau level ≤6 weeks, while the global longitudinal strain continued to decrease in the first 6 months post-onset (median -17.3%, P < 0.001 [versus acute]). At 6 months, 35.7% of the patients still had an abnormal global longitudinal strain, which persisted in 5/9 patients that underwent echocardiography >12-≤18 months post-onset and in 3/3 patients >18-≤24 months post-onset. In a multivariable analysis, soluble troponin T (>62.0 ng/L [median]) was associated with reduced global longitudinal strain at 6 months. Our cardiac MRI findings indicated acute myocardial involvement (increased T1/T2 value) in 77.8% (7/9), which recovered quickly without signs of fibrosis on convalescent cardiac MRIs. Late global longitudinal strain impairment is seen in some multisystem inflammatory syndrome in children patients up to one-year post-onset. Careful cardiac follow-up in patients with elevated troponin in the acute phase and patients with persistent abnormal global longitudinal strain is warranted until resolution of the global longitudinal strain since the long-term implications of such abnormalities are still unclear.

COVID-19 vaccines-associated Takotsubo cardiomyopathy: A narrative review.

Takotsubo cardiomyopathy (TTC) is a severe, acute, reversible, and self-limited cardiac dysfunction. It usually affects postmenopausal women and is mostly triggered by physical or emotional stressors. Following the COVID-19 pandemic, millions of doses of different types of COVID-19 vaccines are being administered globally. There have been reports of different cardiac complications after receiving COVID-19 vaccines. To our knowledge, there have been 16 reported cases of COVID-19 vaccination-associated TTC. In this study, we first provide a brief overview of TTC and then an overview of selected reported TTC cases following COVID-19 vaccinations. It is crucial to highlight that the occurrence of TTC after vaccination does not establish a direct cause-and-effect relationship between immunization and TTC. Further investigations are necessary to examine any potential association between COVID-19 vaccines and the incidence of TTC. Additionally, the benefits of receiving COVID-19 vaccines significantly outweigh the potential risks of developing adverse events.

Randomized controlled trial of remote ischemic preconditioning in children having cardiac surgery

BackgroundChildren undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury.MethodsWe conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass.ResultsThere were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different.ConclusionsThere is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy.Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.

Abstract 16945: Aberrant Citric Acid Cycle Metabolites Temporally Coincide With Myocardial Dysfunction in a Rat Model of Stress Cardiomyopathy

Introduction: Stress cardiomyopathy is characterized by transient contractile dysfunction with a poorly understood mechanism. Targeting metabolic derangements has proven efficacious in chronic heart failure, but the role of metabolism in acute cardiac dysfunction is ill-defined. Hypothesis: Characterizing any metabolic alterations in stress cardiomyopathy may help identify potential therapeutic targets. Methods: Sprague-Dawley rats (350 ± 57 g) were given a single intraperitoneal injection of 75 mg/kg isoprenaline. Animals were allocated into groups (N=30 each) based on designated time-points for assessment after injection: control (no injection), day 1, 3, and 7. Rats underwent left ventricular PV loop catheterization followed by harvesting of apical ventricular tissue. Targeted metabolomic analyses were performed via LC-MS and supplemented with enzyme activity assays, qPCR, and Western blotting. Results: Stroke work, cardiac output, and ejection fraction were all significantly reduced by day 1 with recovery by day 7 (Figure A, all p&lt;0.05). Targeted tissue metabolomics revealed peaks in nearly all citric acid cycle metabolites, pyruvate, and lactate that similarly correlated with illness (Figure B). In tandem, anaplerotic amino acids rose with injury while tissue triglycerides decreased. Pyruvate dehydrogenase phosphorylation decreased with decreased expression of pyruvate dehydrogenase kinase (Figure C). However, no differences were noted in tissue acylcarnitine levels despite increased serum fatty acids (all p&gt;0.05). Conclusions: Profound rises in citric acid metabolites with accompanying increases in anaplerotic amino acids are suggestive of metabolic reprogramming in the setting of energetic deficits. Notably, these trends differ from those found in chronic heart failure, and represent a novel phenotypic characterization of stress cardiomyopathy with potential therapeutic implications.

Immunological characterization of stroke-heart syndrome and identification of inflammatory therapeutic targets.

Acute cardiac dysfunction caused by stroke-heart syndrome (SHS) is the second leading cause of stroke-related death. The inflammatory response plays a significant role in the pathophysiological process of cardiac damage. However, the mechanisms underlying the brain-heart interaction are poorly understood. Therefore, we aimed to analysis the immunological characterization and identify inflammation therapeutic targets of SHS. We analyzed gene expression data of heart tissue 24 hours after induction of ischemia stoke by MCAO or sham surgery in a publicly available dataset (GSE102558) from Gene Expression Omnibus (GEO). Bioinformatics analysis revealed 138 differentially expressed genes (DEGs) in myocardium of MCAO-treated compared with sham-treated mice, among which, immune and inflammatory pathways were enriched. Analysis of the immune cells infiltration showed that the natural killer cell populations were significantly different between the two groups. We identified five DIREGs, Aplnr, Ccrl2, Cdkn1a, Irak2, and Serpine1 and found that their expression correlated with specific populations of infiltrating immune cells in the cardiac tissue. RT-qPCR and Western blot methods confirmed significant changes in the expression levels of Aplnr, Cdkn1a, Irak2, and Serpine1 after MCAO, which may serve as therapeutic targets to prevent cardiovascular complications after stroke.

Galectin-3 contributes to acute cardiac dysfunction and toxicity by increasing oxidative stress and fibrosis in doxorubicin-treated mice

BackgroundDoxorubicin (DOX) leads to cardiovascular toxicity through direct cardiomyocyte injury and inflammation. We aimed to study the role of Galectin-3 (Gal-3), a β-galactosidase binding lectin associated with inflammation and fibrosis in DOX-induced acute cardiotoxicity in mice. MethodsMale C57 and Gal-3 knockout (KO) mice were given a single dose of DOX (15 mg/kg, i.p) or placebo. Serum creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and cardiac thiobarbituric acid-reactive substance (TBARS) were measured at 3 days to assess cardiac injury and oxidative stress. Cardiac remodeling and function were studied by echocardiography and catheterization at 7 days. Myocardial fibrosis was quantified in picrosirius red stained slices. ResultsAbsence of Gal-3 tended to reduce the mortality after DOX. DOX significantly increased CPK, LDH, AST and TBARS while treated Gal-3 KO mice showed reduced injury and oxidative stress. After 7 days, adverse remodeling, fibrosis and dysfunction in treated-C57 mice were severely affected while those effects were prevented by absence of Gal-3. ConclusionIn summary, genetic deletion of Gal-3 prevented cardiac damage, adverse remodeling and dysfunction, associated with reduced cardiac oxidative stress and fibrosis. Understanding the contribution of GAL-3 to doxorubicin-induced cardiac toxicity reinforces its potential use as a therapeutic target in patients with several cancer types.

Life threating onset of Cardiac Sarcoidosis with mediastinal involvement.

We have described a clinical case with atypical onset of sarcoidosis. A young patient presented to the emergency room with acute heart failure and severe cardiac dysfunction simulating dilated cardiomyopathy or severe myocarditis. Hypoxic respiratory failure refractory to oxygen therapy was treated with steroids. The diagnosis was made by a multidisciplinary team who decided to perform EndoBronchial UltraSound-guided TransBronchial Needle Aspiration (EBUS TBNA) in addition to a cardiac MRI. The result was to obtain, in this case, a prompt therapeutic response in order to preserve the patient cardiac function.

MFN2-mediated mitochondrial fusion facilitates acute hypobaric hypoxia-induced cardiac dysfunction by increasing glucose catabolism and ROS production

BackgroundRapid ascent to high-altitude environment which is characterized by acute hypobaric hypoxia (HH) may increase the risk of cardiac dysfunction. However, the potential regulatory mechanisms and prevention strategies for acute HH-induced cardiac dysfunction have not been fully clarified. Mitofusin 2 (MFN2) is highly expressed in the heart and is involved in the regulation of mitochondrial fusion and cell metabolism. To date, however, the significance of MFN2 in the heart under acute HH has not been investigated. Methods and resultsOur study revealed that MFN2 upregulation in hearts of mice during acute HH led to cardiac dysfunction. In vitro experiments showed that the decrease in oxygen concentration induced upregulation of MFN2, impairing cardiomyocyte contractility and increasing the risk of QT prolongation. Additionally, acute HH-induced MFN2 upregulation promoted glucose catabolism and led to excessive mitochondrial reactive oxygen species (ROS) production in cardiomyocytes, ultimately resulting in decreased mitochondrial function. Furthermore, co-immunoprecipitation (co-IP) and mass spectrometry analyses indicated that MFN2 interacted with the NADH-ubiquinone oxidoreductase 23 kDa subunit (NDUFS8). Specifically, acute HH-induced MFN2 upregulation increased NDUFS8-dependent complex I activity. ConclusionsTaken together, our studies provide the first direct evidence that MFN2 upregulation exacerbates acute HH-induced cardiac dysfunction by increasing glucose catabolism and ROS production. General significanceOur studies indicate that MFN2 may be a promising therapeutic target for cardiac dysfunction under acute HH.

Multicolored MIS-C, a single-centre cohort study

BackgroundThe aim of this study was to investigate the clinical and laboratory parameters that can predict the severity of Multisystem Inflammatory Syndrome in Children (MIS-C) at admission.MethodsWe conducted a single-center, partly retrospective, partly prospective, observational cohort study between November 1, 2020 and December 31, 2021, which included patients aged from 1 month to 19 years, meeting the diagnostic criteria of MIS-C. We categorized the patients into three subgroups based on clinical and laboratory markers and assessed the predictive value of these factors in terms of ICU administration and cardiac abnormalities.Results53 patients were classified in the following subgroups: Kawasaki-like disease (group 1) (47.2%, n = 25), shock with or without acute cardiac dysfunction (group 2) (32%, n = 17), fever and inflammation (group 3) (20.8%, n = 11). Subgroup analysis revealed that patients with shock and KD at initial presentation had significantly more severe manifestation of MIS-C requiring intensive care unit (ICU) treatment. Of the initial laboratory values, only CRP showed a significant difference between the 3 clinical groups, being lower in group 3. 52.6% of patients were admitted to the ICU. The median length of ICU stay was 3 days (range 3–20). ICU admission was more likely in patients with shortness of breath, renal failure (AKI) and patients with significantly increased concentrations of ferritin, D-dimer, INR and significantly milder increase concentration of fibrinogen. We found that fibrinogen and ferritin levels are independent risk factors for ICU admission. Cardiac abnormalities were found in 56.6% of total (30/53), with the following findings: decreased left ventricular function (32%), coronary abnormality (11.3%), pericardial effusion (17%), arrhythmia (32.1%) and mitral regurgitation (26.6%). Diarrhea and conjunctivitis at the initial presentation with significantly elevated CRP, Pro-BNP and blood pH concentrations were found to be a potential predisposing factor for decreased cardiac function while Pro-BNP and pH were independent risk factors for MIS-C. Regardless of the initial symptoms of MIS-C, the outcome was generally favorable.ConclusionsClinical characteristics and baseline laboratory values ​​may help identify patients at increased risk for severe disease outcome, such as need for intensive care, presence of shock and decreased cardiac function.Trial registrationParticipation consent was not reqired and ethical considerations were unnecessary, since we did not perform any extra interventions, only the necessary and usual therapeutic and diagnostic methods were used.

Sestrin2 Mediates Metformin Rescued the Age-Related Cardiac Dysfunctions of Cardiorenal Syndrome Type 3.

Acute kidney injury (AKI) leads to acute cardiac injury and dysfunction in cardiorenal syndrome Type 3 (CRS3) through oxidative stress (OS). The stress-inducible Sestrin2 (Sesn2) protein reduces reactive oxygen species (ROS) accumulation and activates AMP-dependent protein kinase (AMPK) to regulate cellular metabolism and energetics during OS. Sesn2 levels and its protective effects decline in the aged heart. Antidiabetic drug metformin upregulates Sesn2 levels in response to ischemia-reperfusion (IR) stress. However, the role of metformin in CRS3 remains unknown. This study seeks to explore how the age-related decrease in cardiac Sesn2 levels contributes to cardiac intolerance to AKI-induced insults, and how metformin ameliorates CRS3 through Sesn2. Young (3-5 months) and aged (21-23 months) C57BL/6J wild-type mice along with cardiomyocyte-specific knockout (cSesn2-/-) and their wild type of littermate (Sesn2f/f) C57BL/6J mice were subjected to AKI for 15 min followed by 24 h of reperfusion. Cardiac and mitochondrial functions were evaluated through echocardiograms and seahorse mitochondria respirational analysis. Renal and cardiac tissue was collected for histological analysis and immunoblotting. The results indicate that metformin could significantly rescue AKI-induced cardiac dysfunction and injury via Sesn2 through an improvement in systolic and diastolic function, fibrotic and cellular damage, and mitochondrial function in young, Sesn2f/f, and especially aged mice. Metformin significantly increased Sesn2 expression under AKI stress in the aged left-ventricular tissue. Thus, this study suggests that Sesn2 mediates the cardioprotective effects of metformin during post-AKI.

Transesophageal Echocardiography Use for Orthotopic Liver Transplant

Impact Statement: Transesophageal echocardiography (TEE) is an invaluable tool used in cardiac surgery. So why is it not consistently used in other high-risk surgeries, such as orthotopic liver transplantation (OLT)? Key Words: Transesophageal echocardiography, Liver graft, Liver transplantation Introduction: This scholarly project observes a high-risk patient undergoing an OLT. Hemorrhage, acute cardiac dysfunction, fluid shifts, and other intraoperative pathologies associated with OLT present many challenges for the anesthesia provider. Therefore, timely identification, evaluation, and intervention of intraoperative pathology are necessary to maintain hemodynamic stability. Traditionally, intra-arterial and pulmonary artery catheters (PACs) were used as hemodynamic monitors. Recently, however, transesophageal echocardiography (TEE) has been used for noncardiac surgery to assess hemodynamic status. The objective of this project is to identify the benefits gained from using TEE during OLT in addition to traditional hemodynamic monitoring techniques (CVP/PAOP) and how these findings affect fluid and medication management. Case Presentation: A 50-year-old female underwent general anesthesia for OLT. The patient’s medical history included cirrhosis, ascites, portal hypertension, portal vein thrombosis, thrombocytopenia, anemia, obesity, and coronary artery disease. Surgical history included splenic embolization and coronary artery bypass graft. The patient was transported to the OR, and standard monitors were applied. Initial VS were as follows: BP 148/75, HR 89, SpO2 92%, RR 24. The patient underwent an uneventful anesthetic induction and intubation. Sevoflurane was used to maintain anesthesia. A radial arterial line and an internal jugular introducer with a PAC were placed. Epinephrine and norepinephrine infusions were used to treat intraoperative hypotension. 1.5 L of 5% albumin, 6 U of packed red blood cells (PRBCs), 5 U of fresh frozen plasma (FFP), and 1 U of platelets were administered. Along with intraarterial blood pressure monitoring, CVP and PA pressure monitoring was used to estimate volume status and treat hypotension. Profound hypotension was treated frequently with vasopressors, fluids, and blood products throughout the case. The patient remained intubated and was transported to the intensive care unit (ICU) postoperatively. Forty-eight hours postoperatively, the patient remained intubated. Due to acute kidney injury, a continuous furosemide infusion and subsequent dialysis were required. Discussion: The reviewed literature provided ample evidence that TEE for OLT can be used to make new intraoperative diagnoses, many of these being difficult to identify by other means. Common findings included intracardiac thrombus (ICT), ventricular dysfunction, and multiple embolic pathologies. Shillcutt et al found that 88% of participants in their study had some form of abnormal TEE finding during OLT. TEE findings were also found to impact fluid and medication administration. Hofer et al found that vasopressor (56%), vasodilator (63%), and fluid management (50%) were all impacted by TEE findings in OLT patients. While evidence was provided to exhibit the efficacy of TEE as an intraoperative monitor, sufficient evidence was not provided to support better patient outcomes based on TEE assessments. This is largely due to a lack of quality observations and controlled research during OLT. The most significant evidence supporting better outcomes was from a retrospective observational cohort study that compared TEE, PAC, and a combined therapy group. The authors found that the patients undergoing OLT with both TEE and PAC had the lowest hospital length of stay (LOS), 30-day mortality, and infusion of fluids. This suggests that the addition of TEE with traditional monitors may be the safest method of hemodynamic monitoring. In the presented case study, the addition of TEE monitoring may have helped diagnose the causes of hemodynamic instability more rapidly and potentially altered medication and fluid administration. While the assumption that timely diagnosis of intraoperative findings leads to better outcomes may be reasonable, higher-powered studies are necessary to verify this assumption. Until beneficial outcomes have been validated, the use of TEE cannot be recommended as a comprehensive intervention for every OLT. However, it should be used based on the anesthesia provider’s judgment along with other monitoring tools. Conflict of Interest: I have no conflict of interest to disclose.