Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin

Alterations in T1 of normal and reperfused infarcted myocardium after Gd-BOPTA versus GD-DTPA on inversion recovery EPI.

This study tested whether Gd-BOPTA/Dimeg or Gd-DTPA exerts greater relaxation enhancement for blood and reperfused infarcted myocardium. Relaxivity of Gd-BOPTA is increased by weak binding to serum albumin. Thirty-six rats were subjected to reperfused infarction before contrast (doses = 0.05, 0.1, and 0.2 mmol/kg). delta R1 was repeatedly measured over 30 min. Gd-BOPTA caused greater delta R1 for blood and myocardium than did Gd-DTPA; clearance of both agents from normal- and infarcted myocardium was similar to blood clearance; plots of delta R1 myocardium/delta R1 blood showed equilibrium phase contrast distribution. Fractional contrast agent distribution volumes were approximately 0.24 for both agents in normal myocardium, 0.98 and 1.6 for Gd-DTPA and Gd-BOPTA, respectively, in reperfused infarction. The high value for Gd-BOPTPA was ascribed to greater relaxivity in infarction versus blood. It was concluded that Gd-BOPTA/Dimeg causes a greater delta R1 than Gd-DTPA in regions which contain serum albumin

Cardiac glycosides provide neuroprotection against ischemic stroke: Discovery by a brain slice-based compound screening platform

We report here the results of a chemical genetic screen using small molecules with known pharmacologies coupled with a cortical brain slice-based model for ischemic stroke. We identified a small-molecule compound not previously appreciated to have neuroprotective action in ischemic stroke, the cardiac glycoside neriifolin, and demonstrated that its properties in the brain slice assay included delayed therapeutic potential exceeding 6 h. Neriifolin is structurally related to the digitalis class of cardiac glycosides, and its putative target is the Na(+)/K(+)-ATPase. Other cardiac glycoside compounds tested also showed neuroprotective activity, although with lower apparent potencies. In subsequent whole-animal studies, we found that neriifolin provided significant neuroprotection in a neonatal model of hypoxia/ischemia and in a middle cerebral artery occlusion model of transient focal ischemia. The neuroprotective potential of Na(+)/K(+)-ATPase is of particular interest because of its known “druggability”; indeed, Food and Drug Administration-approved, small-molecule compounds such as digitoxin and digoxin have been in clinical usage for congestive heart failure and arrhythmias for several decades. Thus, an existing cardiac glycoside or closely related compound could provide an accelerated path toward clinical trial testing for ischemic stroke. Our findings underscore the important role that hypothesis-neutral, high-content, tissue-based screens can play in the identification of new candidate drugs and drug targets for the treatment of diseases for which validated therapeutic pathways are not currently available