Myocardial manganese elevation and proton relaxivity enhancement with manganese dipyridoxyl diphosphate. Ex vivo assessments in normally perfused and ischemic guinea pig hearts.
Manganese (Mn) dipyridoxyl diphosphate (MnDPDP) is the active component of a contrast medium for liver MRI. By being metabolized, MnDPDP releases Mn(2+), which is taken up and retained in hepatocytes. The study examined whether MnDPDP elevates Mn content and enhances proton relaxivity in normal myocardium, but not in ischemic myocardium with reduced coronary flow and impaired metabolism. Isolated guinea pig hearts were perfused at normal flow or low flow, inducing global subtotal ischemia. Ventricular ATP and Mn contents, T(1) and T(2) were measured. At normal flow tissue Mn content increased from the control level of 4.1 to 70.4 micromol/100g dry wt with MnDPDP (3000 microM), while low-flow perfusion with MnDPDP (3000 microM) resulted in a Mn content of 16.6 micromol/100 g dry wt. Prolonged ischemia (35 and 90 min) reduced tissue Mn down to the control level. T(1) shortening closely paralleled myocardial Mn elevations during both normal and low-flow perfusion. The use of a Mn(2+)-releasing contrast agent like MnDPDP may be a promising principle in MRI assessments of myocardial function and viability in coronary heart disease by revealing a differential pattern of changes in T(1) relative to coronary flow, cell Mn uptake and retention, ion channel function and metabolism.
Brurok
H
H
Department of Physiology and Biomedical Engineering, Faculty of Medicine, Norwegian University of Science and Technology, Medisinsk-Teknisk Senter, N-7005 Trondheim, Norway.
Skoglund
T
T
Berg
K
K
Skarra
S
S
Karlsson
J O
JO
Jynge
P
P
D000818:Animals; D003287:Contrast Media; D003326:Coronary Circulation; D004492:Edetic Acid / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008345:Manganese / Q000378:metabolism* / Q000493:pharmacokinetics; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D011522:Protons; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives*; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D003287:Contrast Media; D011522:Protons; D008345:Manganese; D011732:Pyridoxal Phosphate; D004492:Edetic Acid; C060076:N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid