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

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.

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Phenotypic outcomes in CNS serotonin and serotonin-mediated behavior are modulated by gene X environment interactions: A nonhuman primate model

PsycEXTRA Dataset ◽

10.1037/e552512012-012 ◽

2006 ◽

Author(s):

J. Dee Higley ◽

Tim K. Newman

Keyword(s):

Nonhuman Primate ◽

Nonhuman Primate Model ◽

Primate Model ◽

Gene X Environment Interactions

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Maternal High-Fat Diet Persistently Alters Bone Marrow Immune Cell Proportions and Function in a Nonhuman Primate Model

Diabetes ◽

10.2337/db18-222-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 222-OR

Author(s):

MICHAEL J. NASH ◽

TAYLOR K. SODERBORG ◽

RACHEL C. JANSSEN ◽

ERIC M. PIETRAS ◽

JACOB E. FRIEDMAN

Keyword(s):

Bone Marrow ◽

Nonhuman Primate ◽

High Fat Diet ◽

Immune Cell ◽

High Fat ◽

Nonhuman Primate Model ◽

Primate Model ◽

And Function

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Reperfusion plus Selective Intra-arterial Cooling (SI-AC) Improve Recovery in a Nonhuman Primate Model of Stroke

Neurotherapeutics ◽

10.1007/s13311-020-00895-6 ◽

2020 ◽

Author(s):

Di Wu ◽

Yongjuan Fu ◽

Longfei Wu ◽

Mitchell Huber ◽

Jian Chen ◽

...

Keyword(s):

Nonhuman Primate ◽

Nonhuman Primate Model ◽

Primate Model

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Robotic Assessment of Upper Limb Function in a Nonhuman Primate Model of Chronic Stroke

Translational Stroke Research ◽

10.1007/s12975-020-00859-0 ◽

2021 ◽

Author(s):

Yining Chen ◽

Meredith C. Poole ◽

Shelby V. Olesovsky ◽

Allen A. Champagne ◽

Kathleen A. Harrison ◽

...

Keyword(s):

Upper Limb ◽

Nonhuman Primate ◽

Chronic Stroke ◽

Nonhuman Primate Model ◽

Limb Function ◽

Primate Model ◽

Upper Limb Function

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A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection

Experimental Eye Research ◽

10.1016/j.exer.2021.108678 ◽

2021 ◽

pp. 108678

Author(s):

Lakshmi Rajagopalan ◽

Corine Ghosn ◽

Mitalee Tamhane ◽

Alexandra Almazan ◽

Lydia Andrews-Jones ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Blue Light ◽

Delivery System ◽

Nonhuman Primate ◽

Outer Retina ◽

Nonhuman Primate Model ◽

Primate Model

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Transcriptomic phases of periodontitis lesions using the nonhuman primate model

Scientific Reports ◽

10.1038/s41598-021-88803-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jeffrey L. Ebersole ◽

Radhakrishnan Nagarajan ◽

Sreenatha Kirakodu ◽

Octavio A. Gonzalez

Keyword(s):

Gene Expression ◽

Nonhuman Primate ◽

Gingival Crevicular Fluid ◽

Inflammatory Responses ◽

Expression Profiles ◽

Lesion Detection ◽

Gingival Tissue ◽

Specific Gene ◽

Nonhuman Primate Model ◽

Primate Model

AbstractWe used a nonhuman primate model of ligature-induced periodontitis to identify patterns of gingival transcriptomic after changes demarcating phases of periodontitis lesions (initiation, progression, resolution). A total of 18 adult Macaca mulatta (12–22 years) had ligatures placed (premolar, 1st molar teeth) in all 4 quadrants. Gingival tissue samples were obtained (baseline, 2 weeks, 1 and 3 months during periodontitis and at 5 months resolution). Gene expression was analyzed by microarray [Rhesus Gene 1.0 ST Array (Affymetrix)]. Compared to baseline, a large array of genes were significantly altered at initiation (n = 6049), early progression (n = 4893), and late progression (n = 5078) of disease, with the preponderance being up-regulated. Additionally, 1918 genes were altered in expression with disease resolution, skewed towards down-regulation. Assessment of the genes demonstrated specific profiles of epithelial, bone/connective tissue, apoptosis/autophagy, metabolism, regulatory, immune, and inflammatory responses that were related to health, stages of disease, and tissues with resolved lesions. Unique transcriptomic profiles occured during the kinetics of the periodontitis lesion exacerbation and remission. We delineated phase specific gene expression profiles of the disease lesion. Detection of these gene products in gingival crevicular fluid samples from human disease may contribute to a better understanding of the biological dynamics of the disease to improve patient management.

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