Delayed elfects of early infarct-limiting therapies on healing after myocardial infarction

The effect of early infarct-limiting therapy on the hydroxypyroline (OHP, a marker of collagen) content and topography of 7-day-old infarcts was studied in 76 conscious dogs (69 ligated; seven sham operated). Two hours after their left anterior descending coronary arteries were occluded, 69 dogs were randomly assigned to receive 6 hr intravenous infusions of saline (controls; n = 29), lowdose nitroglycerin (NG; n = 13), prostacyclin (PGI2; n = 14), or ibuprofen (IBU; n = 13). Regional OHP (mg/g dry weight) was measured by spectrophotometry, and size of infarction and topography were determined by computerized planimetry. Infarct size was less in the NG, PGI2, and IBU groups compared with that in the saline group, both when measured as a percent of the arteriographic occluded bed (p < .001) and as a percent of the left ventricle (p < .005). For each treatment group (1) the level of OHP was higher (p < .001) in the region of infarction (saline group, 9.9 + 0.7 mg/g; NG group, 14.9 + 1.9 mg/g; PG12group, 12.9 + 0.9 mg/g; IBU group, 10.6 + 1.4 mg/g) than in normal zones (4.4 + 0.2 mg/g), with more (p < .05) OHP in border than center regions, and (2) the total OHP in the infarct zone was linearly related to size of infarction as a percent of the left ventricle (r = .89 to .94). However, the slopes of regressions for the NG, PGI2, and IBU groups were greater (p < .001) than the slope for the saline group. Also, levels of OHP in the infarct zone were greater in the NG than in the saline group (14.9 ± 1.9 vs 9.9 ± 0.7 mg/g, p < .02). Thinning ratios (average infarct/normal wall thickness) were similar in the sham-operated (1.03 ± 0.02), no infarct (1.03 ± 0.03), saline (0.92 ± 0.02), NG (0.94 0.02), and PGI2 (0.96 ± 0.01) groups, and were greater (p ' .02) than the ratio in the IBU group (0.80 ± 0.02). Expansion indexes (infarct/noninfarct containing endocardial segment) were similar in the sham-operated (1.02 ± 0.02), no infarct (1.01 ± 0.03), NG (1.07 ± 0.03), and PGI2 (1.02 ± 0.01) groups and were less (p < .05) than those in the saline (1.20 ± 0.03) and IBU (1.26 ± 0.02) groups. Thus, early therapy with NG, PGI2, or IBU reduced the size of infarction but did not reduce the amount of collagen in the area of infarction by 1 week. Instead, NG appeared to increase collagen content. More importantly, IBU produced more infarct thinning while NG and PGI2 reduced infarct expansion by 1 week. Circulation 72, No. 4, 907-914, 1985. PROGNOSIS in survivors of myocardial infarction might be influenced not only by the size, but also by the collagen content and thickness of the infarct or scar. Although nitroglycerin (NG),1 2 prostacyclin (PGI2)M, and ibuprofen (IBU)4 therapy instituted in the From the Cardiology Division of the Department of Medicine and the Surgical and Medical Research Institute, University of Alberta, Edmonton, Alberta. Supported in part by grants from the Medical Research Council of Canada. Dr. Jugdutt is recipient of a Senior Clinical Investigator Award from the Canadian Heart Foundation. Address for correspondence: Dr. B. Jugdutt, 2C243 Walter MacKenzie Health Sciences Center, Division of Cardiology, University of Alberta, Edmonton, Alberta, T6G 2R7, Canada. Received April 1, 1985; revision accepted June 6, 1985. Presented in part at the Scientific Sessions of the 57th Annual Meeting of the American Heart Association in Miami Beach, November 1984. Vol. 72, No. 4, October 1985 early stages of infarction have been shown to reduce the size of experimental infarction, their effects on collagen content in the infarct zone and topography during the early phase of healing are not known. Infarct "expansion," or thinning, stretching, and dilatation of the infarct, is common in the first week after infarction and is associated with increased early mortality. 'Early therapy with some anti-inflammatory agents has been shown to lead to thinner scars. Specifically, both indomethacin10 and IBU,12 given at 15 min and 3 hr after coronary occlusion, cause marked thinning of 6-week-old infarcts in dogs, although indomethacin increases'3 while IBU reduces4 the size of experimental infarction. More importantly, infarct thinning and expansion after early indometha-