Gadolinium limits myocardial infarction in the rat: Dose–response, temporal relations and mechanisms

Abstract

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 minutes and reperfusing for 120 minutes. Rats (n = 6/group) were administered intravenous Gd (1 to 100 μmol/kg) 15 minutes 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 μmol/kg (52 ± 5% vs. 64 ± 4%), while the dose that reduced IS/AAR maximally was 20 μmol/ kg (44 ± 4%). Gd also reduced IS/AAR when given 1 minute before reperfusion (47 ± 3%) but not when given 10 seconds after reperfusion (60 ± 3%). Cardioprotection was maintained if I-R was delayed 24-72 hours 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.

Gadolinium decreases inflammation related to myocardial ischemia and reperfusion injury

“…Somewhat paradoxically, exogenously added TNF-α is protective during ischemia and reperfusion through mechanisms which involve the JAK/STAT3 pathway, K ATP channels and the mitochondrial permeability transition pore [24,25]. This protective effect of TNF-α may be related to our previous data, which showed that GdCl 3 -induced cardioprotection is dependent upon the activation of JAK-STAT3 and K ATP channels [1]. …”

“…We have previously shown that the optimal cardioprotective dose of GdCl 3 was 20 μmol/kg (Figure 1B) [1]. Therefore, we used this dose for the experiments in this study.…”

Update on the Pathophysiological Role of Intracellular Signaling Pathways in Atherosclerotic Plaques and Ischemic Myocardium

“…These studies further complicate the role of JAK-STAT pathway in the cardioprotection from the ischemic injury. This finding was also confirmed by the lack of activity of the selective JAK inhibitor (AG-490) in modifying the ischemia/reperfusion injury in vivo [84]. Thus, although the JAK-STAT3 pathway has been included as a key component of the Survivor Activating Factor Enhancement (SAFE) pathway for cardiomyocytes [63], this univocal interpretation should be now considered as more controversial.…”

Gadolinium increases the vascular reactivity of rat aortic rings

“…Gadolinium (Gd) is a trivalent lanthanide cation able at 10 µM to block stretch-activated calcium channels (1) and to attenuate post-ischemic myocardial stunning (2). It is currently used as a magnetic resonance contrast medium, gadobenate dimeglumine (Gd-BOPTA) (3), but concern for contrast-induced nephropathy has been reported (4).…”