Effectiveness of Dipyridamole in Reducing the Size of Experimental Myocardial Infarction

ROBERTS, ARTHUR J. M.D.
JACOBSTEIN, JEROME G. M.D.
CIPRIANO, PAUL R. M.D.
ALONSO, DANIEL R. M.D.
COMBES, JOHN R. M.D.
GAY, WILLIAM A. JR. M.D.

From the Departments of Surgery (Cardiothoracic Surgery Division), Radiology and Pathology at the New York Hospital- Cornell Medical Center, New York, New York.

Address for correspondence: Arthur J. Roberts, M.D., Division of Cardiothoracic Surgery, Northwestern Medical School, 303 East Chicago Avenue, Chicago, Illinois 6061 1.

Supported in part by NHLBI contract l-HV-52985, American Heart Association grant 75–940 and a grant from the Master Heart Foundation, Inc.

Received March 10, 1978; revision accepted August 8, 1979.

Circulation 61(2):p 228-236, February 1980.

SUMMARY

The role of vasodilators in reducing the extent of myocardial necrosis after acute coronary occlusion has been controversial. The present study was performed to evaluate the efficacy of dipyridamole in reducing infarct size either 8 or 24 hours after ligation of the left anterior descending (LAD) coronary artery in 12 dogs. On the basis of identical epicardial ST-segment elevations 15 minutes after coronary ligation, the dogs were divided equally into control or dipyridamole-treated (3 mg/kg) groups. Technetium-99m-glucoheptonate (TcGH) was injected intravenously 1 hour after coronary occlusion and myocardial imaging performed before autopsy. Blood pressure (BP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and left ventriculography (VG) were recorded before and at regular intervals after LAD occlusion. Autopsy delineation of myocardial infarct size was determined by planimetry of myocardial slices stained with nitroblue tetrazolium (NBT) and in vivo infarct size was measured by planimetry of myocardial TcGH uptake in the right anterior oblique view.

During the infusion of dipyridamole, mean BP fell in the dipyridamole group from 102 ± 4 to 80 ± 6 mm Hg (p < 0.05) (mean ± SEM), HR decreased from 134 ± 5 to 122 ± 5 beats/min (p < 0.05), tension-time index decreased from 3120 ± 296 to 1839 ± 211 mm Hg-sec/min (p < 0.05) and LVEDP was unchanged, 7.7 ± 0.6 vs 7.9 ± 0.9 mm Hg (NS). VG analysis 1 hour after coronary occlusion revealed less decrease in regional ejection fraction in the anterior wall of dipyridamole-treated animals compared with the control group, −11 + 3% vs −33 ± 5% (p < 0.01), while inferior wall ejection fraction increased in both groups, although more in dipyridamole-treated animals, 30 ± 3% vs 20 ± 5% (p < 0.05). The radionuclide uptake of TcGH was smaller in dipyridamole compared with control animals, 7.9 ± 0.9 vs 16.7 ± 1.0 cm² (p < 0.025), while autopsy-determined infarct weight (NBT technique) was also less, 7.7 ± 1.2 vs 17.6 ± 1.4 g (p < 0.025).

These results document that dipyridamole can favorably alter the course of acute experimental myocardial infarction. The decrease in infarct size can be quantified in vivo and noninvasively by TcGH myocardial imaging and verified postmortem by the NBT histochemical staining technique.