A Transonic flow probe (Crystal Biotech Inc) was placed on the vessel to continuously monitor blood flow.
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The left anterior descending coronary artery was dissected free over a 1- to 2-cm interval. Baseline angiography was performed to precisely define the anatomy. A 7F left coronary bypass catheter (Cordis) was positioned via a right carotid approach. Surgery was performed with electrocardiographic and arterial pressure monitoring under general anesthesia in accordance with Association for Accreditation and Assessment of Laboratory Animal Care laboratory standards. 4 5 This study was performed to evaluate the feasibility of Tc-99m DMP-444 imaging in the identification of activated platelets at the site of a coronary lesion using a canine model of endothelial injury.Ī canine model was chosen because of the species-specificity of DMP-444. Tc-99m DMP-444 can be detected in arterial and venous thrombi by nuclear imaging as early as 15 minutes after injection. DMP-444 is a cyclic peptide, protease-resistant, selective GP IIb/IIIa receptor inhibitor that has been labeled with technetium (Tc)-99 m. Labeling an inhibitor of the platelet glycoprotein (GP) IIb/IIIa receptor could theoretically overcome some of these difficulties. 3 Fibrin, platelets, and fibrinolytic molecules have been targets for labeling, 3 but cumbersome technology, poor target-to-blood pool ratios, and low sensitivity were encountered. 2 A diagnostic test that could reliably detect the underlying acute coronary lesion would be useful.Ī variety of approaches to imaging arterial thrombi have been developed, but none has been successful enough to be adopted into clinical practice. These diagnostic tools are imperfect, resulting in the inappropriate admission or discharge of patients with acute coronary syndromes, as well as delays in treatment. 1 The diagnosis of acute coronary syndromes is based on secondary phenomena such as symptoms, electrocardiographic evidence, and serum markers of myocyte injury.
Unstable angina and myocardial infarction are initiated by plaque rupture or erosion, with overlying platelet thrombus deposition severe enough to impede coronary flow and to induce ischemia. The 10 animals with negative images had lower counts, smaller thrombus weights ( P<0.05 for each), and fewer platelets by electron microscopy.Ĭonclusions-Activated platelets participating in acute thrombus formation can be accurately detected by nuclear imaging using Tc-99 m DMP-444. In 10 animals with markedly positive nuclear images after the injection of Tc-99m DMP-444, the presence of platelet-rich thrombus was confirmed postmortem by gross appearance, high nuclear counts, and abundant platelets on electron microscopy. Methods and Results-Combinations of a flow-limiting stenosis and 0 to 15 minutes of endothelial electrical stimulation at a site in the left anterior descending coronary artery were used to induce varying amounts of thrombus formation. We tested the ability of a new glycoprotein IIb/IIIa platelet inhibitor DMP-444, labeled with technetium (Tc)-99 m, to identify platelet-rich thrombus by nuclear imaging in a canine model.
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