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

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Abstract
The hypothesis that prostaglandin inhibition by indomethacin (I) increases infarct size in a conscious dog was studied by measuring the anatomic risk region, infarct size and collateral flow. Instrumented dogs (45) were divided into 3 groups: 21 were pretreated with I (10 mg/kg i.v.), 10 were given only the vehicle (V) (0.1 M Na3PO4 buffer) and were controls (C). The left circumflex (LC) coronary artery was permanently occluded in all dogs. After the dogs were sacrificed 2 days later, the occluded LC bed was defined by stereoscopic coronary arteriography. The masses of infarct (MI), risk region (R) and left ventricle (LV) were calculated by planimetry from areas of weighed transverse sections of LV. Total MI was greater in I dogs (23.2 .+-. 2.7 g (SEM [standard error of the mean]), 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 3 groups. The relation was similar for C and V dogs (MI = 0.50 R - 8.07, r [correlation coefficient] = 0.96, n = 20), but the slope was greater (P < 0.001) in I dogs (MI = 1.15 R - 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 subepicardial and lateral directions within R and this effect was uniform from base to apex of LV. Hemodynamic changes were similar in all 3 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. Collateral flow changes, measured using 9-.mu. radioactive microspheres, were not signicicantly different in the 3 groups. The mechanism by which I increases infarct size may be related to increased O2 demands and possible cellular membrane effects rather to effects on collateral flow.