Manganese-enhanced MRI of mouse heart during changes in inotropy.
Recently the dual properties of manganese ion (Mn(2+)) as an MRI contrast agent and a calcium analogue to enter excitable cells has been used to mark specific cells in brain and as a potential intracellular cardiac contrast agent. Here the hypothesis that in vivo manganese-enhanced MRI (MEMRI) can detect changes in inotropy in the mouse heart has been tested. T(1)-weighted images were acquired every minute during an experimental time course of 75 min. Varying doses of Mn(2+) (3.3-14.0 nmoles/min/g BW) were infused during control and altered inotropy with dobutamine (positive inotropy due to increased calcium influx) and the calcium channel blocker diltiazem (negative inotropy). Infusion of MnCl(2) led to a significant increase in signal enhancement in mouse heart that saturated above 3.3 +/- 0.1 nmoles/min/g BW Mn(2+) infusion. At the highest Mn(2+) dose infused there was a 41-47% increase in signal intensity with no alteration in cardiac function as measured by MRI-determined ejection fractions. Dobutamine increased both the steady-state level of enhancement and the rate of MRI signal enhancement. Diltiazem decreased both the steady-state level of enhancement and the rate of MRI signal enhancement. These results are consistent with the model that Mn(2+)-induced enhancement of cardiac signal is indicative of the rate of calcium influx into the heart. Thus, the simultaneous measurement of global function and calcium influx using MEMRI may provide a useful method of evaluating in vivo responses to inotropic therapy.
Hu
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TC
Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Pautler
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RG
MacGowan
G A
GA
Koretsky
A P
AP
D000818:Animals; D002712:Chlorides; D004110:Diltiazem; D004280:Dobutamine; D006321:Heart / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds; D051379:Mice; D009200:Myocardial Contraction
D002712:Chlorides; D017895:Manganese Compounds; D004280:Dobutamine; D004110:Diltiazem; C025340:manganese chloride