Gadolinium limits myocardial infarction in the rat: dose-response, temporal relations and mechanisms. J Mol Cell Cardiol 2008 Feb;44(2):345-51
Date
12/18/2007Pubmed ID
18083188Pubmed Central ID
PMC2322938DOI
10.1016/j.yjmcc.2007.11.002Scopus ID
2-s2.0-39149132834 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
The lanthanide cation, gadolinium (Gd) attenuates post-ischemic myocardial stunning. This study tests the hypothesis that Gd also preconditions the myocardium against infarction following ischemia-reperfusion (IR) and explores potential mechanisms underlying Gd-induced cardioprotection. Regional myocardial infarction was induced in rats by occluding the left anterior descending artery for 30 min and reperfusing for 120 min. Rats (n=6/group) were administered intravenous Gd (1 to 100 micromol/kg) 15 min prior to ischemia. Hearts were excised after reperfusion to determine infarct size (IS) and area at risk (AAR). The ratio IS/AAR (%) was reduced by Gd in a "U"-shaped, dose-dependent manner. The minimum dose that reduced IS/AAR was 5 micromol/kg (52+/-5% vs. 64+/-4%), while the dose that reduced IS/AAR maximally was 20 micromol/kg (44+/-4%). Gd also reduced IS/AAR when given 1 min before reperfusion (47+/-3%) but not when given 10 s after reperfusion (60+/-3%). Cardioprotection was maintained if IR was delayed 24-72 h after Gd administration. Cardioprotection by Gd was abolished by inhibition of JAK-2 with AG-490, of p42/44 MAPK with PD98059 or of K(ATP) channels with glibenclamide. None of these agents given alone altered IS/AAR compared with controls. Inhibition of JAK-2 also blocked Gd-induced delayed cardioprotection. Gd may have broad potential roles in IR, as it conferred immediate cardioprotection when given prior to ischemia or prior to reperfusion and delayed cardioprotection for up to 72 h after administration. The mechanism underlying Gd-induced preconditioning appears to be multi-factorial, involving JAK-2, STAT-3 and p44 MAPK pathways, as well as K(ATP) channels.
Author List
Nicolosi AC, Strande JL, Hsu A, Fu X, Su J, Gross GJ, Baker JEAuthor
John E. Baker PhD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCardiotonic Agents
Dose-Response Relationship, Drug
Gadolinium
Hemodynamics
In Vitro Techniques
Janus Kinase 2
Male
Myocardial Infarction
Myocardial Ischemia
Potassium Channels
Rats
Rats, Sprague-Dawley
STAT Transcription Factors
Time Factors
