Severity dependent increases in circulating cardiac troponin I and MMP-9 concentrations after experimental acute pulmonary thromboembolism.
BACKGROUND
Making the diagnosis of acute pulmonary thromboembolism (APT) and assessing its severity is very challenging. While cardiac troponin I (cTnI) concentrations are promising in risk stratification, no previous study has examined whether there is a linear relation between cTnI concentrations and the severity of APT. Moreover, matrix metalloproteinases (MMPs) are involved in the pathophysiology of APT. However, it is unknown whether the increases in MMP concentrations after APT reflect the severity of this condition. We examined whether the circulating concentrations of these biomarkers increase in proportion to the severity of experimental APT induced in anesthetized dogs.


METHODS
APT was induced with autologous blood clots (saline, 1, 3, or 5 ml/kg) injected into the right atrium. Hemodynamic evaluations were carried out for 120 min. Gelatin zymography of MMP-2 and MMP-9 from plasma samples were performed and serum cTnI concentrations were determined at baseline and 120 min after APT.


RESULTS
While no significant increases in pro-MMP-2 concentrations were found after APT, pro-MMP-9 concentrations increased by 80% only after 5 ml/kg of clot embolization. Serum cTnI and plasma pro-MMP-9 concentrations correlated positively with pulmonary vascular resistance (P=0.007 and rs=0.833 for troponin I, and P=0.034 and rs=0.684 for pro-MMP-9) and with pulmonary artery pressure (P=0.005 and rs=0.610 for troponin I, and P=0.022 and rs=0.720 for pro-MMP-9).


CONCLUSIONS
Circulating cTnI and pro-MMP-9 increase in proportion to the severity of APT, although the increases in plasma pro-MMP-9 are less clear with less severe APT. These findings may be relevant for clinical APT.
Uzuelli
Juliana A
JA
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, Brazil.
Dias-Junior
Carlos A C
CA
Tanus-Santos
Jose E
JE
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D011655:Pulmonary Embolism / Q000097:blood* / Q000139:chemically induced / Q000473:pathology*; D019210:Troponin I / Q000097:blood*
D019210:Troponin I; D020780:Matrix Metalloproteinase 9; D010100:Oxygen