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Myocardial drug distribution pattern following intrapericardial delivery: an MRI analysis
John D Gleason1, Khanh P Nguyen, Kraig V Kissinger
1Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, USA.
Objectives:
The main goal was to gain insights into the pharmacokinetics of intrapericardial drug delivery using magnetic resonance (MR) imaging analysis and the extracellular MR contrast agent gadopentetate dimeglumine (Gd-DTPA) as a model.
Background:
Recent development of catheter-based techniques to access the intact pericardial space has increased interest in intrapericardial delivery for local cardiac therapy. Distribution and myocardial penetration of intrapericardial agents are not well characterized.
Methods:
The intact pericardial space was percutaneously accessed through the right atrial appendage in ten anesthetized pigs, following which 5 mL Gd-DTPA (N = 8) or normal saline as control (N = 2) were administered. Animals were sacrificed at 1, 3, 3.5, 5, or 8 hr. The whole heart was excised, washed with normal saline, and the chambers distended with saline-filled bags. Myocardial penetration of Gd-DTPA was analyzed by a series of short-axis T1-weighted turbospin-echo MR images.
Results:
At 1, 3, and 3.5 hr after Gd-DTPA, a uniform ring of enhancement was found along the epicardium, with a depth density related to time after administration. No contrast ring was visible at 5 or 8 hr or in control animals. Transmural myocardial T1 values obtained 5 hr after Gd-DTPA administration were reduced, suggesting that Gd-DTPA had penetrated uniformly throughout the myocardium.
Conclusions:
Intrapericardial administration results in relatively uniform distribution of an agent across the ventricular epicardium. The depth of penetration is consistent with functional evidence that epicardial structures can be targeted by this technique.