Effect of indomethacin on collateral blood flow and infarct size in the conscious dog

The authors examined the hypothesis that prostaglandin inhibition by indomethacin (I) increases infarct size in a conscious dog in which the anatomic risk region, infarct size, and collateral flow can be measured. They randomized 45 instrumented dogs into three groups: 21 were pretreated with I (10 mg/kg i.v.), 10 were given only the vehicle (V) (0.1 M sodium phosphate buffer), and 14 were controls (C). Acute permanent occlusion of the left circumflex (LC) coronary artery was made in the conscious state in all dogs. After the dogs were sacrificed 2 days later, the occluded LC bed was defined by stereoscopic coronary arteriography. The mass of infarct (MI), risk region (R), and left ventricle (LV) were calculated from planimetered areas of weighed transverse sections of LV. Total MI was greater in the I dogs (23.2 ± 2.7 g (SEM), n = 15) than in V dogs (15.6 ± 2.2 g, n = 10, p < 0.05) and C dogs (11.8 ± 1.8 g, n = 10, p < 0.005). The masses of R and LV did not differ significantly between groups. MI was directly related to R in all three groups. The relation was similar for C and V dogs (MI = 0.50R - 8.07, r = 0.96, n = 20), but the slope was greater (p < 0.001) in I dogs (MI = 1.15R - 23.86, r = 0.92, n = 15), indicating that for R of any size, infarct size was greater in I dogs than in C and V dogs. Morphologically, I increased infarct size in both subepicardial and lateral directions within R, and this effect was uniform from base to apex of LV. Hemodynamic changes followed similar trends in all three groups, with slightly higher postocclusion mean arterial pressure (p < 0.05) and heart rate (p < 0.1) in I dogs than V and C dogs. Changes in collateral flow, measured using 9-μ radioactive microspheres, were not significantly different in the three groups. The mechanism by which I increases infarct size appears to be related to increased oxygen demands and possible cellular membrane effects rather than effects on collateral flow.