Early Recovery of Regional Performance in Salvaged Ischemic Myocardium following Coronary Artery Occlusion in the Dog

Abstract

A B S T R A C T Although numerous agents have been shown experimentally to protect ischemic myocardium, a critical unanswered question is whether function is preserved in the salvaged tissue. Accordingly, 38 openchest dogs had measurements of percent segment length shortening (%SS) and velocity of segment length shortening either in midmyocardial or subepicardial and subendocardial ischemic segments before and after 60 min of left anterior descending coronary artery occlusion during 5 h of reperfusion; 10 additional dogs were subjected to 3 h of coronary occlusion followed by 72 h ofreperfusion. 15 min after coronary artery occlusion, radiolabeled microspheres were injected into the left atrium for measurement of regional myocardial blood flow, and dogs were treated with 1 mg/kg i.v. (n = 23) of an anti-inflammatory drug, flurbiprofen or an equal volume of saline (n = 25). The ischemic myocardiumat-risk for necrosis was determined by injecting methylene blue dye into the left atrium with the coronary artery reoccluded at the end of the reperfusion period, slicing the left ventricle into thin transverse sections, and measuring the areas of each slice that were not perfused (pink unstained tissue) by methylene blue. The quantity of necrotic tissue in each transverse section was measured by planimetry after incubation ofthe slices in triphenyltetrazolium chloride, and by direct histological examination in dogs with 72 h of reperfusion.Regional myocardial blood flow of the ischemic segments between the ultrasonic dimension crystals was similar in treated (0.34+0.03 ml/min per g) and control dogs (0.35+0.03 ml/min per g). In saline-treated control dogs subjected to a 1-h coronary occlusion, 17.9+1.8% of the myocardium-at-risk became necrotic. but in flurbiprofen-treated dogs none of the tissue became necrotic. In saline-treated dogs passive lengthening of the previously ischemic segments persisted through 5 h of reperfusion in all three regions of myocardium after a 1-h coronary occlusion. In flurbiprofen-treated dogs regional function returned to normal within 5 min of reperfusion in both the subendocardium (%SS preocclusion = 17.2±2.0%; 5 min reperfusion = 17.8+3.1%; P = NS) and in the midmyocardium (%SS preocclusion = 17.8±+2.2%; 5 min reperfusion = 17.9+2.3%; P = NS) and was not significantly different after 5 h of reperfusion from what it was before coronary occlusion. In the subepicardium oftreated dogs regional function began to improve within 15 min of drug administration even during coronary occlusion. Regional function was not different from preocclusion values after either 5 min or 5 h of reperfusion (%SS preocclusion = 21.0±2.4%; 5 min reperfusion = 20.6 ±+3.8%; P = NS). In dogs subjected to 3 h of coronary occlusion and 72 h of reperfusion, the administration of flurbiprofen was also associated with significantly smaller infarcts and a significantly more rapid rate of functional recovery than in control dogs.Thus, it appears that flurbiprofen not only decreased the quantity of necrosis in tissue made isc...

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