ISCHEMIA AND ACTIVATED NEUTROPHILS ALTER CORONARY MICROVASCULAR BUT NOT EPICARDIAL CORONARY-ARTERY REACTIVITY

Activated neutrophils have been implicated in reperfusion injury and t he no-reflow phenomenon of intramyocardial arterioles. This study test ed the hypothesis that ischemia and activated neutrophils impair coron ary endothelial and smooth muscle cell function of epicardial and intr amyocardial coronary arteries. Alteration of smooth muscle and endothe lial cell function in epicardial coronary arteries (3 mm diameter) and intramyocardial coronary arteries (0.3 mm diameter) was compared by m eans of a myograph after exposure to ischemia (epicardial, 160 minutes ; intramyocardial, 30 minutes), activated neutrophils, and combined is chemia and activated neutrophils. Morphologic studies at the ultrastru ctural level were done by means of scanning electron microscopy. Epica rdial coronary artery function was normal after ischemia, storage,vith activated neutrophils, and ischemia followed by storage with activate d neutrophils. Intramyocardial artery function, however, was altered. Contraction to a 45 mmol/L concentration of potassium chloride after i schemia and storage with activated neutrophils was increased (p = 0.06 ). Smooth muscle relaxation was significantly decreased after ischemia , but storage with activated neutrophils did not further decrease smoo th muscle relaxation. Endothelium-dependent relaxation to bradykinin w as significantly decreased after combined ischemia and incubation with activated neutrophils (p < 0.05). Sensitivity to bradykinin was decre ased after both ischemia alone (p < 0.05) and activated neutrophils al one (p < 0.05). Similar morphologic alterations were found in epicardi al and intramyocardial arteries after ischemia. Activated neutrophils alone minimally damaged endothelial cells of nonischemic intramyocardi al and epicardial arteries. Endothelial cells of both arteries exposed to ischemia alone showed evidence of ischemic damage, including endot helial cell blebbing, nuclear bulging, and appearance of large holes i n the cell surface. Severe endothelial cell damage was found after com bined ischemia and storage with neutrophils: total destruction of cell s and exposure of the basal lamina. Endothelial damage, therefore, cor related with artery function in intramyocardial but not in epicardial arteries. These results indicate that ischemia is a prerequisite for s evere neutrophil injury of intramyocardial artery endothelium-mediated relaxation. This may explain no-reflow phenomenon in arterioles concu rrent with myocardial reperfusion injury.