Author + information
- Stephen G. Ellis, MD1,
- Claudia I. Henschke, MD, PhD1,2,
- Tamas Sandor, DP1,2,
- Joshua Wynne, MD, FACC1,*,
- Eugene Braunwald, MD, FACC1 and
- Robert A. Kloner, MD, PhD, FACC1,3
- ↵3Address for reprints: Robert A. Kloner, MD, PHD, Harvard Medical School, 180 Longwood Avenue. Room 235. Boston, Massachusetts 02115.
To characterize the functional and biochemical recovery of myocardium salvaged by reperfusion, 19 anesthetized mongrel dogs underwent 2 hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for up to 2 weeks. Thirteen dogs had a permanent occlusion and served as the control group. All dogs had serial two-dimensional echocardiograms and in vivo biopsies for adenosine triphosophate (ATP) and creatine phosphate after occlusion and at the time of sacrifice (6 hours, n = 15; 7 days, n = 6; or 14 days after occlusion, n = 11). The area of necrosis and area at risk of necrosis were identified in dogs sacrificed at 6 hours.
After 4 hours of reperfusion, the area of necrosis determined by the triphenyltetrazolium chloride technique, expressed as a function of the area at risk by in vivo monastral blue injection, was 23.9 ± 5.8% (mean ± standard error of the mean) and largely subendocardial, compared with 89.1 ± 5.3% in dogs with permanent (6 hour) occlusion (probability [p] < 0.001), in which it was transmural. Myocardial contractility was assessed by measuring systolic wall thickening by computer-assisted two-dimensional echocardiography. Before occlusion, this variable averaged 47.9 ± 6.3% in the region to become ischemic. An early salutary effect of reperfusion in the central ischemic zone was seen as a decrease in wall thinning from -11.9 ± 2.9%, 90 minutes after occlusion, to -7.4 ± 2.0%, 4 hours after reperfusion, contrasted with a change from -6.2 ± 3.3%, 90 minutes after occlusion, to -11.7 ± 3.3%, 6 hours after occlusion in the permanently occluded group (p < 0.05). Active thickening was not observed until 72 hours of reperfusion (13.1 ± 4.6%); this increased to 19.5 ± 2.8% at 14 days, compared with 1.5 ± 5.9% in the permanently occluded group at this time (p < 0.05). However, preocclusion values were not achieved in the reperfused group. Some recovery of ATP in the salvaged subepicardium was also noted, with return of levels from 8.0 ±1.9 nmol/mg protein, 90 minutes after occlusion, to 13.2 ± 1.8 nmol/mg protein, after 4 hours of reperfusion (p < 0.05); however, 7 days were required for recovery approaching preocclusion values of 34.9 ± 1.9 nmol/mg protein.
Thus, reperfusion after 2 hours of coronary occlusion resulted in recovery of jeopardized myocardium, in which the deterioration of function observed in nonreperfused tissue was reversed and biochemical improvement occurred over the course of 2 weeks. Computer-assisted two-dimensional echocardiography, a noninvasive but quantitative technique, appears well suited to monitor the rate of functional recovery of myocardium salvaged by reperfusion.
↵* Dr. Wynne is a Young Investigator of the National Heart, Lung, and Blood Institute. This work was done during the tenure of Dr. Kloner as an Established Investigator from the American Heart Association, Dallas, Texas and with funds contributed in part by the Massachusetts Heart Association, Boston, Massachusetts.
This work was supported in part by Grants HL 23140 and SCOR 26215 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland and by Grant GM 18674 from the National Institute of General Medical Science, Bethesda, Maryland.
- American College of Cardiology Foundation