Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.
Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.
D000380:Agranulocytosis / Q000503:physiopathology; D000818:Animals; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D005112:Extracorporeal Circulation; D005609:Free Radicals / Q000378:metabolism; D006098:Granulocytes / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology*; D009200:Myocardial Contraction; D013481:Superoxides / Q000378:metabolism
D005609:Free Radicals; D013481:Superoxides