Format

Send to

Choose Destination
Am J Respir Crit Care Med. 2017 Sep 1;196(5):609-620. doi: 10.1164/rccm.201701-0104OC.

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling.

Author information

1
1 Division of Pulmonary Diseases and Critical Care Medicine.
2
2 Division of Pulmonary Diseases and Critical Care Medicine, South Texas Veterans Health Care System, San Antonio, Texas.
3
3 Department of Microbiology, The University of Alabama at Birmingham School of Medicine, Birmingham, Alabama.
4
4 Critical Care Medicine, Hospital Universitari de Tarragona Joan XXIII, Rovira i Virgili University, Tarragona, Spain.
5
5 Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Tarragona, Spain.
6
6 Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Abu Dhabi, United Arab Emirates.
7
7 School of Medicine, University of Dundee, Dundee, United Kingdom.
8
8 Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
9
9 Cardio-thoracic Unit and Adult Cystic Fibrosis Centre, Milan, Italy.
10
10 Istituti di Ricovero e Cura a Carattere Scientifico, Granada Ospedale Maggiore Policlinico, Milan, Italy.
11
11 Division of Pulmonary Diseases, Department of Medicine, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain.
12
12 Department of Pathology, and.
13
13 Texas Biomedical Research Institute, San Antonio, Texas.
14
14 Division of Pulmonary and Critical Care Medicine, Yale University, New Haven, Connecticut.
15
15 Royal Perth Hospital Unit, University of Western Australia, Perth, Australia; and.
16
16 Department of Infectious Diseases and Pulmonary Medicine and.
17
17 SFB-TR84 "Innate Immunity of the Lung," Charité-Universitätsmedizin Berlin, Berlin, Germany.
18
18 Department of Immunology and Microbiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Abstract

RATIONALE:

Up to one-third of patients hospitalized with pneumococcal pneumonia experience major adverse cardiac events (MACE) during or after pneumonia. In mice, Streptococcus pneumoniae can invade the myocardium, induce cardiomyocyte death, and disrupt cardiac function following bacteremia, but it is unknown whether the same occurs in humans with severe pneumonia.

OBJECTIVES:

We sought to determine whether S. pneumoniae can (1) translocate the heart, (2) induce cardiomyocyte death, (3) cause MACE, and (4) induce cardiac scar formation after antibiotic treatment during severe pneumonia using a nonhuman primate (NHP) model.

METHODS:

We examined cardiac tissue from six adult NHPs with severe pneumococcal pneumonia and three uninfected control animals. Three animals were rescued with antibiotics (convalescent animals). Electrocardiographic, echocardiographic, and serum biomarkers of cardiac damage were measured (troponin T, N-terminal pro-brain natriuretic peptide, and heart-type fatty acid binding protein). Histological examination included hematoxylin and eosin staining, immunofluorescence, immunohistochemistry, picrosirius red staining, and transmission electron microscopy. Immunoblots were used to assess the underlying mechanisms.

MEASUREMENTS AND MAIN RESULTS:

Nonspecific ischemic alterations were detected by electrocardiography and echocardiography. Serum levels of troponin T and heart-type fatty acid binding protein were increased (P < 0.05) after pneumococcal infection in both acutely ill and convalescent NHPs. S. pneumoniae was detected in the myocardium of all NHPs with acute severe pneumonia. Necroptosis and apoptosis were detected in the myocardium of both acutely ill and convalescent NHPs. Evidence of cardiac scar formation was observed only in convalescent animals by transmission electron microscopy and picrosirius red staining.

CONCLUSIONS:

S. pneumoniae invades the myocardium and induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in an NHP model of severe pneumonia.

KEYWORDS:

Streptococcus pneumoniae; cardiovascular complications; community-acquired pneumonia; pneumococcal pneumonia

PMID:
28614669
PMCID:
PMC5620668
DOI:
10.1164/rccm.201701-0104OC
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center