Severe pneumococcal pneumonia causes acute cardiac toxicity and subsequent cardiac remodeling

Luis F. Reyes, Marcos I. Restrepo, Cecilia A. Hinojosa, Nilam J. Soni, Antonio Anzueto, Bettina L. Babu, Norberto Gonzalez-Juarbe, Alejandro H. Rodriguez, Alejandro Jimenez, James D. Chalmers, Stefano Aliberti, Oriol Sibila, Vicki T. Winter, Jacqueline J. Coalson, Luis D. Giavedoni, Charles S. Dela Cruz, Grant W. Waterer, Martin Witzenrath, Norbert Suttorp, Peter H. DubeCarlos J. Orihuela

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)609-620
Number of pages12
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number5
StatePublished - Sep 1 2017


  • Cardiovascular complications
  • Community-acquired pneumonia
  • Pneumococcal pneumonia
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Pulmonary and Respiratory Medicine


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