scholarly journals 2473 Cardiac injury due to Streptococcus pneumoniae invasion during severe pneumococcal pneumonia in a novel nonhuman primate model

2018 ◽  
Vol 2 (S1) ◽  
pp. 6-6
Author(s):  
Luis F. Reyes ◽  
Cecilia A. Hinojosa ◽  
Nilam J. Soni ◽  
Julio Noda ◽  
Vicki T. Winter ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Troponin I ◽  
Cardiac Injury ◽  
Severe Pneumonia ◽  
Cardiac Events ◽  
Cardiac Damage ◽  
Nonhuman Primate Model ◽  
Primate Model ◽  
Adverse Cardiac Events

OBJECTIVES/SPECIFIC AIMS: The aims of this study are (1) to develop and characterize a novel nonhuman primate model of pneumococcal pneumonia that mimics human disease; and (2) determine whether Streptococcus pneumoniae can: (a) translocate to the heart, (b) cause adverse cardiac events, (c) induce cardiomyocyte death, and (d) lead to scar formation during severe pneumonia in baboons. METHODS/STUDY POPULATION: Six adult baboons (Papio cynocephalus) were surgically tethered to a monitoring system to continuously assess their heart rate, temperature, and electrocardiogram (ECG). A baseline transthoracic echocardiogram, 12-lead ECG, serum troponin-I levels, brain natriuretic peptide, and heart-type fatty acid binding protein (HFABP) levels were obtained before infection and at the end of the experiment to determine cardiovascular damage during pneumococcal pneumonia. Animals were challenged with 108 colony-forming units of S. pneumoniae in the right middle lobe using flexible bronchoscopy. Three baboons were rescued with ampicillin therapy (80 mg/kg/d) after the development of pneumonia. Cardiac damage was confirmed by examination of tissue sections using immunohistochemistry as well as electron and fluorescence microscopy. Western-blots and tissue staining were used to determine the presence of necroptosis (RIP3 and pMLKL) and apoptosis (Caspase-3) in the cardiac tissue. Cytokine and chemokine levels in the heart tissue were determined using Luminex technology. RESULTS/ANTICIPATED RESULTS: Four males (57%) and three (43%) females were challenged. The median age of all baboons was 11 (IQR, 10-19) years old, which corresponds to a middle-aged human. Infected baboons consistently developed severe pneumonia. All animals developed systemic inflammatory response syndrome with tachycardia, tachypnea, fever, and leukocytosis. Infection was characterized by initial leukocytosis followed by severe leukopenia on day 3 postinoculation. Non-specific ischemic alterations by ECG (ST segment and T-wave flattering) and in the premortem echocardiogram were observed. The median (IQR) levels of troponin I and HFABP at the end of the experiment were 3550 ng/mL (1717–5383) and 916.9 ng/mL (520.8–1323), respectively. Severe cardiomyopathy was observed using TEM and H&E stains in animals with severe pneumonia. Necroptosis was detected in cardiomyocytes of infected animals by the presence of pMLKL and RIP3 in cardiac tissues. Signs of cardiac remodeling indicated by disorganized collagen deposition was present in rescued animals but not in the other animals. DISCUSSION/SIGNIFICANCE OF IMPACT: We confirmed that baboons experience cardiac injury during severe pneumococcal pneumonia that is characterized by myocardial invasion, activation of necroptosis, and tissue remodeling in animals rescued by antimicrobial therapy. Cardiac damage by invading pneumococci may explain why adverse cardiac events that occur during and after pneumococcal pneumonia in adult human patients.

Troponin I Levels Increase After Experimental Pneumococcal Pneumonia Infection in a Nonhuman Primate Model

CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 228A
Author(s):  
Marcos Restrepo ◽  
Luis Reyes ◽  
Cecilia Hinojosa ◽  
Jessica Perry ◽  
Robert Shade ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Pneumococcal Pneumonia ◽  
Troponin I ◽  
Nonhuman Primate Model ◽  
Primate Model

Abstract 16344: Pericardial Complications in Patients With COVID-19: A Systematic Review of Published Cases

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sandeep Singh ◽  
Akhil Jain ◽  
Priyanka Chaudhari ◽  
Faizan Ahmad Malik ◽  
Virmitra Desai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pericardial Effusion ◽  
Cardiac Tamponade ◽  
Troponin I ◽  
Case Reports ◽  
Cardiac Injury ◽  
Pericardial Tamponade ◽  
Time Interval ◽  
Cardiac Damage ◽  
St Segment Elevation

Introduction: COVID-19 has been linked to cardiac damage and life-threatening pericardial complication on which data are trivial which incited us to perform this review of published case reports. Methods: PubMed/Medline, Web of Science and SCOPUS were searched until June 2020 for case reports on COVID-19-associated pericarditis, cardiac tamponade or pericardial effusion. Results: We identified 8 articles reporting 11 COVID-19 positive cases [mean age: 51.4±14.3 (34-78 yrs) 5 male/6 female)] with pericardial complications. All (100%) cases were COVID-19 positive at the presentation with ~80% having dyspnea, chest pain and cough. Time interval from first symptom to pericardial effusion was 7±8 (1-26) days. Five patients reported heart failure with reduced EF on echocardiography with mean LVEF 36.25%±8.54%. All patients showed nearly normal Troponin-I without angiographically significant stenosis except one. Out of 8 cases on echocardiography 4 cases reported with diffuse hypokinesia, 2 reported inferior and inferolateral walls hypokinesia and 2 reported signs of pericardial tamponade. Out of 11 patients, cardiovascular risk factors in the form of diabetes or hypertension or obesity were present in 5 patients. Cardiovascular comorbidities such as heart failure with low ejection fraction, non-ischemic cardiomyopathy and prior myocarditis were present in 3 patients. ST-segment elevation in 3, sinus tachycardia in 2, T wave inversion in 1 case were noted. Four patients developed cardiac tamponade, 1 developed takotsubo syndrome and 3 patients died. Conclusions: COVID-19 patients had signs of a high burden of cardiac injury. Pericardial complications (pericardial effusion and cardiac tamponade) remain infrequent complications which may require prompt care to avoid mortality.

scholarly journals Minor elevations in troponin I are associated with mortality and adverse cardiac events in patients with atrial fibrillation

2011 ◽  
Vol 32 (5) ◽  
pp. 611-617 ◽  
Author(s):  
E. J. van den Bos ◽  
A. A. Constantinescu ◽  
R. T. van Domburg ◽  
S. Akin ◽  
L. J. Jordaens ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Troponin I ◽  
Cardiac Events ◽  
Adverse Cardiac Events

scholarly journals Potential New Approaches in Predicting Adverse Cardiac Events One Month after Major Vascular Surgery

2018 ◽  
Vol 28 (1) ◽  
pp. 63-69
Author(s):  
Mladjan Golubovic ◽  
Velimir Peric ◽  
Dragana Stanojevic ◽  
Milan Lazarevic ◽  
Nenad  Jovanovic ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Vascular Surgery ◽  
Troponin I ◽  
Risk Index ◽  
Cardiac Complications ◽  
Cardiac Events ◽  
Preoperative Risk ◽  
Adverse Cardiac Events ◽  
Creatine Kinase Mb ◽  
Major Vascular Surgery

Objective: The aim of our study was to find the best model with sufficient power to improve the risk stratification in major vascular surgery patients during the first 30 days after this procedure. The discriminatory power of 4 biomarkers (troponin I [TnI], N-terminal prohormone of brain natriuretic peptide [NT-proBNP], creatine kinase-MB isoenzyme [CK-MB], high-sensitivity C-reactive protein [hs-CRP]) was tested as well as 2 risk assessment models and 13 different combinations of them. Subjects and Methods: The study included 122 patients (77% men, 23% women) with an average age of 67.03 ± 4.5 years. An aortobifemoral bypass was performed in 6.56% of the patients, a femoropopliteal bypass in 18.85%, and 49.18% received open surgical reconstruction of the carotid arteries. A total of 25.41% of the patients were given an aortobi-iliac bypass. Results: During the first 30 days, 13 patients (10.7%) had 17 cardiac complications. The most common complication was the new onset of atrial fibrillation (35.3%). During the first 10 days, 10 patients had 1 complication and 2 patients had 2 cardiac events, while 1 patient had 3 complications. By comparing combinations of scores and markers, it was shown that revised cardiac risk index (RCRI) + Vascular Portsmouth Physiological and Operative Severity Score (V-POSSUM) + hsTnI and RCRI + V-POSSUM + hsTnI + NT-proBNP with 100% sensitivity, > 80% specificity had the best discriminatory ability (AUC 0.924 and 0.933, respectively; p < 0.001 for both models) for cardiac complications during the 30 days after surgery. Conclusion: Combinations of traditional preoperative risk factors and scores can enhance the assessment of major adverse cardiac events (MACE) in patients preparing for large vascular surgery. Using only one risk score in these patients seems to be underperforming in preoperative risk assessment.

Role of biomarkers in cardioncology

2011 ◽  
Vol 49 (12) ◽  
Author(s):  
Daniela Cardinale ◽  
Michela Salvatici ◽  
Maria T. Sandri
Keyword(s):  
Troponin I ◽  
Cardiac Injury ◽  
Left Ventricular ◽  
Cardiac Biomarkers ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Current Standard ◽  
Converting Enzyme Inhibitors ◽  
Ventricular Ejection Fraction

AbstractCardiotoxicity is a serious adverse effect of anticancer drugs, impacting on quality of life and overall survival of cancer patients. According to the current standard for monitoring cardiac function, cardiotoxicity is usually detected only when a functional impairment has already occurred, precluding any chance of preventing its development. Over the last decade, however, a new approach, based on the use of cardiac biomarkers, has emerged, and has proven to be an effective alternative strategy for early detection of subclinical cardiac injury. In particular, the role of troponin I in identifying patients at risk of cardiotoxicity and of angiotensin-converting enzyme inhibitors in preventing left ventricular ejection fraction reduction and late cardiac events represent an effective tool for the prevention of this complication.

scholarly journals Toll-Like Receptor 4 Agonistic Antibody Promotes Innate Immunity against Severe Pneumonia Induced by Coinfection with Influenza Virus and Streptococcus pneumoniae

2013 ◽  
Vol 20 (7) ◽  
pp. 977-985 ◽  
Author(s):  
Akitaka Tanaka ◽  
Shigeki Nakamura ◽  
Masafumi Seki ◽  
Kenji Fukudome ◽  
Naoki Iwanaga ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Influenza Virus ◽  
Streptococcus Pneumoniae ◽  
Pneumococcal Pneumonia ◽  
Survival Rates ◽  
Severe Pneumonia ◽  
Histopathological Study ◽  
Toll Like Receptor ◽  
Content Type ◽  
Monocyte Chemoattractant Protein 1

ABSTRACTCoinfection with bacteria is a major cause of mortality during influenza epidemics. Recently, Toll-like receptor (TLR) agonists were shown to have immunomodulatory functions. In the present study, we investigated the effectiveness and mechanisms of the new TLR4 agonistic monoclonal antibody UT12 against secondary pneumococcal pneumonia induced by coinfection with influenza virus in a mouse model. Mice were intranasally inoculated withStreptococcus pneumoniae2 days after influenza virus inoculation. UT12 was intraperitoneally administered 2 h before each inoculation. Survival rates were significantly increased and body weight loss was significantly decreased by UT12 administration. Additionally, the production of inflammatory mediators was significantly suppressed by the administration of UT12. In a histopathological study, pneumonia in UT12-treated mice was very mild compared to that in control mice. UT12 increased antimicrobial defense through the acceleration of macrophage recruitment into the lower respiratory tract induced by c-Jun N-terminal kinase (JNK) and nuclear factor kappaB (NF-κB) pathway-dependent monocyte chemoattractant protein 1 (MCP-1) production. Collectively, these findings indicate that UT12 promoted pulmonary innate immunity and may reduce the severity of severe pneumonia induced by coinfection with influenza virus andS. pneumoniae. This immunomodulatory effect of UT12 improves the prognosis of secondary pneumococcal pneumonia and makes UT12 an attractive candidate for treating severe infectious diseases.

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