Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular remodeling, and impairs systolic function...

Area of Science:

• Cardiology
• Pharmacology
• Biomedical Science

Background:

• Cyclooxygenase (COX)-2 expression elevates in the heart post-myocardial infarction (MI).
• COX-2 inhibition in murine MI models demonstrated preservation of left ventricular dimensions and function.

Purpose of the Study:

• To investigate the impact of selective COX-2 inhibition on left ventricular remodeling and function in a pig model of MI.

Main Methods:

• Twenty-two pigs underwent MI induction via coronary artery ligation.
• Animals were treated with a COX-2 inhibitor (celecoxib) or placebo for 6 weeks.
• Cardiac function, dimensions, infarct size, and collagen density were assessed using echocardiography, conductance catheters, and histological staining.

Main Results:

• COX-2 inhibition led to a significant increase in mortality (50% vs. 0%) compared to controls.
• While infarct size was similar, COX-2 inhibition resulted in greater thinning of the infarcted myocardial wall.
• Left ventricular remodeling was enhanced, with increased end-diastolic and end-systolic volumes, indicating impaired systolic function.
• Infarct collagen density was significantly reduced in the COX-2 inhibitor group.

Conclusions:

• Selective COX-2 inhibition post-MI in pigs is linked to increased mortality.
• The treatment promoted adverse left ventricular remodeling and impaired systolic function.
• Decreased infarct collagen fiber density is a likely mechanism underlying these detrimental effects.