Rationale: Up to one-third of the 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.
Objective: 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 post-antibiotic treatment during severe pneumonia using a non-human primates (NHP) model.
Methods: We examined cardiac tissue from six adult NHP with severe pneumococcal pneumonia and three uninfected controls. Three animals were rescued with antibiotics (convalescent animals). Electrocardiogram (ECG), echocardiogram, and serum biomarkers of cardiac damage were performed (troponin-T, NT-proBNP and H-FABP). Histologic examination included hematoxylin & eosin (H&E) staining, immunofluorescence, immunohistochemistry, picosirus red staining and transmission electron microscopy (TEM). Immunoblots were used to assess the underlying mechanisms.
Measurements and Main Results: Non-specific ischemic alterations were detected by ECG and echocardiogram. Serum levels of troponin-T and H-FABP levels were increased (p=<0.05) after pneumococcal infection in both, acutely-ill and convalescent NHP. S. pneumoniae was detected in the myocardium of all NHP with acute severe pneumonia. Necroptosis and apoptosis were detected in myocardium of both, acutely-ill and convalescent NHP. Evidence of cardiac scar formation was observed only in convalescent animals by TEM and picosirus red staining.
Conclusions: S. pneumoniae invades the myocardium, induces cardiac injury with necroptosis and apoptosis, followed by cardiac scarring after antibiotic therapy, in a non-human primate model of severe pneumonia.
|Number of pages||12|
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Early online date||14 Jun 2017|
|Publication status||Published - 1 Sep 2017|
- Community acquired pneumonia
- Streptococcus pneumoniae
- Cardiovascular complications
- Pneumococcal pneumonia