TY - JOUR
T1 - Severe pneumococcal pneumonia causes acute cardiac toxicity and subsequent cardiac remodeling
AU - Reyes, Luis F.
AU - Restrepo, Marcos I.
AU - Hinojosa, Cecilia A.
AU - Soni, Nilam J.
AU - Anzueto, Antonio
AU - Babu, Bettina L.
AU - Gonzalez-Juarbe, Norberto
AU - Rodriguez, Alejandro H.
AU - Jimenez, Alejandro
AU - Chalmers, James D.
AU - Aliberti, Stefano
AU - Sibila, Oriol
AU - Winter, Vicki T.
AU - Coalson, Jacqueline J.
AU - Giavedoni, Luis D.
AU - Dela Cruz, Charles S.
AU - Waterer, Grant W.
AU - Witzenrath, Martin
AU - Suttorp, Norbert
AU - Dube, Peter H.
AU - Orihuela, Carlos J.
N1 - Publisher Copyright:
Copyright © 2017 by the American Thoracic Society.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 caninvade themyocardium, 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) causeMACE, 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 anNHP model of severe pneumonia.
AB - 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 caninvade themyocardium, 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) causeMACE, 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 anNHP model of severe pneumonia.
KW - Cardiovascular complications
KW - Community-acquired pneumonia
KW - Pneumococcal pneumonia
KW - Streptococcus pneumoniae
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U2 - 10.1164/rccm.201701-0104OC
DO - 10.1164/rccm.201701-0104OC
M3 - Article
C2 - 28614669
AN - SCOPUS:85028686769
SN - 1073-449X
VL - 196
SP - 609
EP - 620
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
IS - 5
ER -