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Updated: May 12, 2026
A Porcine Model of Acute Autologous Pulmonary Embolism
Published on: September 6, 2024
Doxycycline prevents acute pulmonary embolism-induced mortality and right ventricular deformation in rats
Stefany B A Cau1, Renan C Barato, Mara R Celes
1Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.
Purpose:
Acute pulmonary embolism (APE) is a critical cardiopulmonary condition associated with right ventricular (RV) failure and death. While pharmacological inhibition of matrix metalloproteinases (MMPs) attenuated APE-induced hemodynamic alterations, no previous study has evaluated whether this approach decreases APE-induced mortality and RV deformation. We tested this hypothesis in rats.
Methods:
Wistar rats received an intraperitoneal injection of 30 mg/kg doxycycline (or saline) and after 30 min a sterile suspension of 300 μm microsphere (21 mg/kg or saline) was injected into the tail vein. After 24 h, surviving animals were killed and the RVs were collected and used for histological and morphometric analyses. RV samples were also homogenized and assayed by SDS-polyacrilamide gel electrophoresis gelatin zymography to evaluate MMP-2 and MMP-9 activity. In situ zymography was carried out in RV to assess MMP activity and neutrophil accumulation in myocardial tissue was determined by myeloperoxidase activity measurement. Dihydroethidium was used to assess RV reactive oxygen species concentrations.
Results:
APE caused 72.5% mortality during the first hour of follow up. Pretreatment with doxycycline was associated with significant decrease in APE-induced mortality rate to 50% (P<0.05). Embolized animals showed significant RV dilation, and pretreatment with doxycycline blunted this alteration (P<0.05). APE increased the number of RV neutrophils and MMP-9 levels (P<0.05). Pretreatment with doxycycline blunted APE-induced increases in RV myocardial ROS concentrations and MMP gelatinolytic activity (both P<0.05).
Conclusions:
These findings show that MMP inhibition with doxycycline protects against APE-induced mortality and RV enlargement. These beneficial effects are probably due to attenuation of APE-induced oxidative stress and increases in ventricular proteolytic activity and suggest that doxycycline may have promising protective effects in patients with APE.
Insights
Matrix metalloproteinase (MMP) inhibition with doxycycline reduced mortality and right ventricular (RV) enlargement in a rat model of acute pulmonary embolism (APE). This suggests doxycycline may protect against APE-induced RV failure.
Area of Science:
- Cardiology
- Pulmonology
- Pharmacology
Background:
- Acute pulmonary embolism (APE) is a life-threatening condition characterized by right ventricular (RV) failure.
- Matrix metalloproteinases (MMPs) play a role in APE pathophysiology, but their inhibition's effect on mortality and RV deformation is unknown.
Purpose of the Study:
- To investigate the efficacy of doxycycline, an MMP inhibitor, in reducing mortality and RV deformation in a rat model of APE.
Main Methods:
- Wistar rats were treated with doxycycline or saline before microsphere-induced APE.
- RV histology, morphometry, MMP activity (zymography), neutrophil infiltration, and reactive oxygen species (ROS) were assessed.
Main Results:
- APE caused 72.5% mortality; doxycycline reduced this to 50%.
- Doxycycline attenuated APE-induced RV dilation, neutrophil infiltration, MMP-9 levels, and ROS concentrations.
Conclusions:
- MMP inhibition with doxycycline protects against APE-induced mortality and RV enlargement.
- Doxycycline's benefits may stem from reduced oxidative stress and ventricular proteolytic activity, suggesting potential clinical utility in APE patients.
