Figure 4

Effect of Heart Rate Reduction on Manganese Contrast Enhancement. A and B. The HCN channel inhibitor ZD 7288 significantly reduced mid point contrast enhancement in all mouse groups (**P<0.01 versus without ZD 7288), and this was accompanied by significant reductions in heart rate also in all groups (**P<0.01 versus heart rate pre ZD 7288) (WT N = 8, mdx N = 9, Sgcd−/− N = 10). C and D. When the time course of manganese contrast enhancement and heart rate in the wild type and Sgcd−/− mice is examined we can see that the ZD 7288 reduces heart rate in the Sgcd−/− mice to the same level as wild type mice from the time of starting the manganese infusion, though during the first 5 minutes there is still a significantly higher level of manganese contrast enhancement in the Sgcd−/− mice compared to WT (**P<0.01). This indicates that whereas heart rate is an important factor in the extent of manganese contrast enhancement, in the Sgcd−/− mice there is at least some component of increased cellular uptake of manganese per heart beat compared to WT.