LABORATORY INVESTIGATION NUCLEAR CARDIOLOGY Intrinsic washout rates of thallium-201 in normal and ischemic myocardium after dipyridamole- induced vasodilation

Infusion of dipyridamole has been suggested as an alternative to exercise stress for myocardial perfusion imaging for detection of ischemia, but the mechanism and significance of thallium-201 (201T1) redistribution after administration of dipyridamole are uncertain. If disparate intrinsic cellular efflux rates of 201TI from normal and relatively underperfused myocardium in response to dipyridamole-induced vasodilation were observed, this could explain delayed 201TI redistribution. We investigated the effect of an intravenous infusion of 0.15 mg/kg dipyridamole on the intrinsic myocardial washout rate of 201 Tl as measured with a gamma-detector probe after intracoronary injection (50 ,uCi) of the radionuclide in open-chested anesthetized dogs. In six normal dogs the t/2 for intrinsic 201T1 washout from the myocardium was 89 11 min (SE) at control conditions and became more rapid at 59 + 10 min (p = .0001) after dipyridamole. This corresponded to a significant increase in microsphere-determined epicardial (0.95 ± 0.11 to 2.23 ± 0.46 ml/min/g; p = .01) and endocardial (0.86 ± 0.10 to 1.53 0.27; p = .029) flows. In 12 dogs with a critical coronary stenosis, the 201T1 intrinsic washout rate slowed from 70 + 5 to 108 + 6 min (p = .0001) after production of the stenosis and slowed even further to 169 ± 21 min (p = .003) after dipyridamole. Compared to conditions with the stenosis alone, dipyridamole-induced vasodilation caused a fall in mean aortic pressure (91 + 5 to 74 + 6 mm Hg; p < .0001), a fall in coronary perfusion pressure (60 + 4 to 45 ± 3 mm Hg), but an unchanged total coronary flow (53 ± 8 to 52 8 ml/min; p = NS) and stenosis gradient, and hence, stenosis resistance. Although transmural flow was unaltered in the stenotic region after dipyridamole, epicardial flow increased from 1.00 0.18 to 1.27 ± 0.47 ml/min/g and endocardial flow fell from 0.65 + 0.15 to 0.50 ± 0.22 ml/min/g, resulting in an endocardial/epicardial flow gradient. In the range of transmural flow values between 0. 10 and 1 .4 ml/min/g, the intrinsic 20 Tl washout rate became more prolonged as flow decreased. Thus, in the presence of a critical coronary stenosis, the dipyridamole-induced fall in systemic arterial pressure and distal coronary perfusion caused a subnormal endocardial blood flow and ischemia, resulting in a prolonged intrinsic myocardial 201T1 efflux rate. The disparate 201T1 efflux rates in normal and underperfused myocardium can explain delayed redistribution observed after dipyridamole infusion in the presence of a coronary stenosis. Circulation 71, No. 2, 378-386, 1985. MYOCARDIAL perfusion imaging has been performed during coronary vasodilation produced by intravenously administered dipyridamole both for detecting coronary artery disease"'2 and for identifying high-risk patients after myocardial infarction.'3 This potent coronary vasodilator enhances regional myocardial blood flow in zones supplied by normal coronary arteries but not in myocardium perfused by obstructed vessels, resulting in flow inhomogeneity. Since the From the Experimental Cardiology Laboratory, Division of Cardiology, Department of Internal Medicine, University of Virginia Medical Center, Charlottesville. Supported in part by USPHS grant lROI HL-26205-03. Address for correspondence: George A. Beller, M.D._ University of Virginia Medical Center, Division of Cardiology, Box 158, Charlottesville, VA 22908. Received June 15, 1984; revision accepted Oct. 18, 1984. 378 initial myocardial distribution of intravenously administered thallium-201 (20'Tl) is proportional to blood flow,'4 15 scintigraphic defects are observed that demonstrate this relative hypoperfusion. Wel6 and others 12, 17. 1 have demonstrated that under conditions of a coronary stenosis in canine preparations of ischemia or in humans, dipyridamoleor adenosine-induced vasodilation results not only in diminished 201T1 uptake but also in subsequently delayed redistribution similar to that observed with exercise scintigraphy. Redistribution defects have also been demonstrated on serial myocardial scintigrams in patients with coronary artery disease receiving dipyridamole before administration of 201T1.8 The mechanism and significance of 201T1 redistribution after dipyridamole imaging are uncertain. Total CIRCULATION by gest on A ril 6, 2017 http://ciajournals.org/ D ow nladed from LABORATORY INVESTIGATION-NUCLEAR CARDIOLOGY blood flow in a stenotic vessel is not decreased after intravenous infusion of dipyridamole.'6 Furthermore, myocardial oxygen demand is not increased in response to the drug. The duration of active vasodilation may be more prolonged than that induced by exercise. Dipyridamole as well as adenosine are known to produce a significant endocardial-to-epicardial flow gradient distal to a coronary stenosis.19-27 This may produce regions of subendocardial ischemia adjacent to regions of normal or even enhanced epicardial flow. In an earlier study of serial myocardial needle biopsy specimens from anesthetized dogs with a critical left anterior descending coronary stenosis,16 we showed that when 201T1 was injected intravenously after infusion of dipyridamole, net clearance of 20l1T1 from the region of stenosis was slower than that from normal myocardium. The difference in net clearance rates resulted in normalization of the initial defect (redistribution). This could be the result of altered delivery of the tracer to the myocardium (blood flow), of altered extraction of the tracer by the myocardium, or of alterations in the intrinsic efflux of 201T1 from the myocardium. It is not possible to infer the mechanism of redistribution after intravenous injection of the tracer in an intact animal because only the net effect of continuous exchange and recirculation can be observed in such a preparation. The intracellular efflux of 20'T1 can be investigated by using intracoronary rather than intravenous injections of the radionuclide.8 This method effectively eliminates systemic recirculation of 201T1 and allows the determination of intrinsic cellular efflux rates. These rates can then be combined with the values of net myocardial clearance to more completely define the mechanism of thallium uptake and washout in the closed system in the presence of systemic recirculation. Accordingly, the purpose of these experiments was to measure the intrinsic 201T1 washout rates and alterations in regional blood flow during dipyridamoleinduced vasodilation. Disparate efflux rates of 201TI in normal and relatively underperfused myocardial regions in response to the drug could explain the delayed 201T1 redistribution that is seen when the radionuclide is administered intravenously under similar hemodynamic and regional flow conditions.