Beneficial effects associated with matrix metalloproteinases inhibition as coadjuvant to inotropic therapy dring acute pulmonary embolism

• Grant number: 08/10937-1
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2009
• End date: December 31, 2011
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Jose Eduardo Tanus dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Acute pulmonary embolism is a critical condition that is associated with high mortality rates and high morbidity. This condition results from the migration of emboli to the lungs, thus obstructiong pulmonary blood flow and increasing pulmonary arterial pressure and pulmonary vascular resistance. Many ohter factors conctribute to the pulmonary hypertension. These factors include vasoactive factors and hypoxic pulmonary vasoconstriction. Death results from acute pulmonary embolism when right ventricule failure supevines, which is associated with right ventricular contractile dysfunction. Recent results have implicated matrix metalloproteinases in the pathophysiology of acute pulmonary embolism. These enzymes may be activated in the right ventricule and degrade contractile proteins. In this project, we will examine whether matrix metalloproteinases inhibition with doxycycline produces beneficial effects through protection of myocardial cells from protein degradation. Moreover, we will examine whether inotropic drugs produce improved effects on myocardial function when MMPs are inhibited during acute pulmonary embolism. (AU)