Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog

Area of Science:

• Cardiology
• Immunology
• Physiology

Background:

• Regional ventricular dysfunction, or stunned myocardium, is a persistent issue after ischemia and reperfusion.
• Superoxide radical damage is implicated as a key mechanism in this injury.

Purpose of the Study:

• To investigate if granulocytes are a direct source of injury in stunned myocardium.
• To determine the role of granulocytes in myocardial stunning using a 15-minute ischemia dog model.

Main Methods:

• Compared regional function during ischemia and reperfusion with and without granulocytes using extracorporeal coronary perfusion and Leukopak filters.
• Ensured consistent flow reduction, reperfusion flow, preload, afterload, and inotropic stimulation between experimental conditions.

Main Results:

• Agranulocytic perfusion (no granulocytes) prevented myocardial stunning, with function exceeding pre-ischemic levels.
• When granulocytes were present (10% of normal count), stunning occurred, with only 76% return of function.
• Extracorporeal perfusion itself did not prevent stunning, as granulocyte-replete perfusion resulted in <75% function return.

Conclusions:

• Granulocytes are the direct source of injury in stunned myocardium.
• Granulocytes appear to be the main source of superoxide contributing to injury in this model.
• Other potential mechanisms include granulocyte-induced capillary no-reflow and enzyme-mediated damage.