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Super-normal 201Tl retention in hibernating myocardium: an ex-vivo study using the failing human heart
O Parodi1, R De Maria, R Testa
1C.N.R. Clinical Physiology Institute, Milan Section, Niguarda Hospital, Italy. ifcnigmi@tin.it
Insights
This study reveals that "hibernating" myocardium in ischemic heart disease patients shows higher than expected thallium-201 (201Tl) retention, suggesting cellular adaptation to chronic low blood flow.
Area of Science:
- Cardiology
- Nuclear Medicine
- Pathophysiology
Background:
- Delayed thallium-201 (201Tl) distribution is linked to myocardial blood flow in acute ischemia.
- Its behavior in chronic hypoperfusion of human myocardium remains unevaluated.
Purpose of the Study:
- To assess the relationship between delayed 201Tl retention, blood flow, and fibrosis in chronically hypoperfused human myocardium.
- To compare these parameters in ischemic heart disease (IHD) patients versus idiopathic dilated cardiomyopathy (IDC) controls.
Main Methods:
- Evaluated 201Tl retention (4h redistribution), myocardial blood flow (using 99mTc-labeled microspheres), and fibrosis in excised human hearts.
- 201Tl activity was normalized to regions with highest flow and least fibrosis.
Main Results:
- A significant inverse relationship was found between fibrosis and 201Tl activity (r = -0.62, P = 0.0001).
- In IHD patients, a subset of segments (flow/201Tl mismatch) exhibited disproportionately high 201Tl retention relative to blood flow.
- These mismatch segments had less fibrosis than areas with concordant low flow and 201Tl activity.
Conclusions:
- Super-normal 201Tl retention in hibernating myocardium may represent a cellular adaptation mechanism to chronic hypoperfusion.
- This finding has implications for understanding myocardial viability in chronic ischemic conditions.
Objective:
Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated.
Methods:
In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis.
Results:
Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion.
Conclusions:
This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.