Changes in first-pass interstitial kinetics of DTPA in myocardium submitted to low-flow ischemia.

OBJECTIVES: This study aimed to determine the changes during ischemia in the myocardial first-pass kinetics of DTPA, an extracellular tracer that is currently used for assessing myocardial perfusion with magnetic resonance imaging (Magnevist). MATERIALS AND METHODS: Using an indicator-dilution technique, first-pass kinetics of DTPA were compared between normoxia (n=11) and low-flow ischemia (n=11) in isolated rabbit hearts perfused with red blood cell-enhanced perfusate. RESULTS: There was no difference between ischemia and normoxia in the interstitial extraction and clearance rates of DTPA. Interstitial distribution volume of DTPA was, however, lower in ischemia than in normoxia (in percent of myocardial volume: 15+/-11% vs 25+/-11%, P=0.02) as a result of a relationship with coronary flow (P<0.001). CONCLUSIONS: During low-flow myocardial ischemia, DTPA kinetics are unchanged, except for the interstitial distribution volume that is decreased, presumably because of the shrinkage of extracellular fluid. These kinetic properties are favorable for detecting myocardial ischemia at rest with magnetic resonance imaging.

Low-flow ischaemia has no deleterious effect on the steady-state kinetics of 201Tl and 99mTc sestamibi within myocardial tissue.

OBJECTIVES: This study aimed to specifically analyse the impact of low-flow ischaemia on the ability of myocytes to trap and accumulate Tl and sestamibi (MIBI) within myocardial tissue. METHODS: In order to reach steady-state conditions for the interstitial/cellular concentration ratios (Ci/Cc) of the tracers and thereby simulate the conditions of cell cultures studies, Tl and MIBI were injected continuously during an 80 min period within the coronary circulation of isolated hearts submitted to normoxia (n=7) or low-flow ischaemia (n=7; >50% reduction in coronary flow). Ci was determined by using interstitial microdialysis and Cc was determined from Ci and myocardial retention values of the tracers. RESULTS: At the end of the experiments, under steady-state conditions, Ci/Cc was equivalent between low-flow ischaemia and normoxia for both Tl (ischaemia, 0.60 +/- 0.25% vs normoxia, 0.63 +/-0.34%; NS) and MIBI (ischaemia, 1.00 +/- 0.68% vs normoxia, 0.76 +/- 0.32%, NS), whereas tissue concentrations of ATP were more than 4-fold lower in ischaemia than in normoxia (5.1 +/- 3.5 nmol.g vs 22.5 +/- 4.8 nmol.g; P< 0.001). CONCLUSIONS: In contrast to the published results concerning the effects of anoxia on cell cultures, low-flow ischaemia within myocardial tissue has no deleterious effects on the ability of the cells to accumulate Tl and MIBI under steady-state conditions. This gives definitive evidence of the negligible impact of cellular metabolic disorders in the decrease in Tl or MIBI uptake, which is documented by stress-SPECT within low-flow ischaemic myocardium.

201Tl SPECT abnormalities, documented at rest in dilated cardiomyopathy, are related to a lower than normal myocardial thickness but not to an excess in myocardial wall stress.

UNLABELLED: This study was aimed at determining whether the (201)Tl SPECT abnormalities documented in patients with dilated cardiomyopathy are related to a local excess in wall stress, which might act against the diastolic perfusion of myocardium. METHODS: We included 6 healthy volunteers and 7 patients with idiopathic dilated cardiomyopathy who underwent (201)Tl SPECT at rest. On a 13-segment division of the left ventricle, indices of wall stress and tension were calculated at end-diastole by applying Laplace's law, with thickness and curvature radii being determined for each segment on 2 orthogonal MRI slices. RESULTS: Among all patients, 21 analyzed segments had (201)Tl SPECT defects (D+) and 67 had none (D-). Myocardial thickness was lower in D+ (0.88 +/- 0.30 cm) than in D- (1.23 +/- 0.33 cm, P = 0.0002) or in segments from healthy volunteers (0.99 +/- 0.15 cm, P = 0.04). The index of end-diastolic wall tension was also lower in D+ (2.5 +/- 1.0 N.m(-1).mm Hg(-1)) than in D- (3.3 +/- 1.1 N.m(-1).mm Hg(-1), P = 0.02) or in segments from healthy volunteers (3.2 +/- 1.2 .m(-1).mm Hg(-1)) P = 0.04). Last, the index of end-diastolic wall stress, determined by the ratio of wall tension index to myocardial thickness, was equivalent in D+, in D-, and in segments from healthy volunteers (respectively, 3.0 +/- 1.4, 2.8 +/- 1.2, and 3.2 +/- 1.6 hN.m(-2).mm Hg(-1)). CONCLUSION: In patients with dilated cardiomyopathy, the abnormalities documented by (201)Tl SPECT at rest are related to a lower than normal wall thickness and not to an excess in wall stress or tension. Therefore, partial-volume effects are likely to induce these abnormalities, and they may be unrelated to any insufficiency of myocardial perfusion.

(201)Tl and (99m)Tc-MIBI retention in an isolated heart model of low-flow ischemia and stunning: evidence of negligible impact of myocyte metabolism on tracer kinetics.

UNLABELLED: It is not known whether cellular metabolic disorders play a role in the decreased tracer uptake that is documented by conventional SPECT during low-flow ischemia or stunning. This study sought to determine the impact of low-flow ischemia and stunning on the kinetics of (201)Tl and MIBI across the plasma membrane of myocytes. METHODS: The global myocardial retention (Rf) of (201)Tl and MIBI was determined in isolated working hearts from rabbits, perfused with red blood cell-enhanced solution. Experiments were performed in normoxia, with physiological values of coronary flow (N; n = 16); in low-flow ischemia, with a >50% reduction of coronary flow and a > or =20-mm Hg fall in systolic left ventricle pressure (L; n = 15); and in stunning, with 15 min of acute ischemia followed by reperfusion (S; n = 15). Concentration ratios across the plasma membrane of myocytes were also determined for both tracers and expressed as Ci/Cc, where Ci is interstitial activity determined with microdialysis, and Cc is activity from cellular space determined from Rf and Ci values. RESULTS: There was a slight increase in average values of Ci/Cc in ischemia, but not in stunning, for (201)Tl (L, 0.011 +/- 0.006 vs. N, 0.006 +/- 0.004 [P < 0.05]; S, 0.007 +/- 0.004 vs. N [not significant]) and for MIBI (L, 0.011 +/- 0.008 vs. N, 0.005 +/- 0.004 [P < 0.05]; S, 0.005 +/- 0.003 vs. N [not significant]). Moreover, ischemia and stunning had no deleterious effects on the average values of global myocardial retention for (201)Tl (L, 0.63 +/- 0.09 vs. N, 0.50 +/- 0.14 [P < 0.05]; S, 0.59 +/- 0.10 vs. N [P < 0.05]) or for MIBI (L, 0.45 +/- 0.10 vs. N, 0.31 +/- 0.09 [P < 0.05]; S, 0.41 +/- 0.12 vs. N [P < 0.05]). In fact, these values were significantly enhanced in the 2 situations. CONCLUSION: The kinetics of (201)Tl and MIBI across the plasma membrane of myocytes were affected only poorly by low-flow ischemia and not at all by stunning, without any deleterious effects on myocardial retention of both tracers. During low-flow ischemia or stunning, therefore, the information provided by (201)Tl or MIBI SPECT is expected to depend on myocardial perfusion but not on cellular metabolic disorders.