Dobutamine‐induced stress affects intracellular uptake of manganese: A quantitative magnetic resonance imaging study in pigs

Abstract

Purpose: To determine whether there are differences in increase in longitudinal relaxation rate (⌬R1) in the myocardium between bolus administration of Mn 2ϩ ions during rest and during dobutamine-induced stress and, additionally, to determine whether there are differences in ⌬R1 between bolus injection and infusion of Mn 2ϩ ions during dobutamine-induced stress. Materials and Methods:Pigs were divided into three groups with six pigs in each group. All animals received 15 mol MnCl 2 /kg of body weight (b.w.) intravenously either as a bolus injection (groups 1 and 2) or as an infusion over one minute (group 3). The animals in groups 2 and 3 were subjected to dobutamine stress before injection of MnCl 2 , while those in group 1 were not given dobutamine. T1 was quantified in the myocardium and left ventricular blood pool before contrast injection and repeatedly during a one-hour postinjection period.Results: A significant difference in ⌬R1 between the groups with and the group without dobutamine stress was noted in the myocardium up to 45 minutes after contrast agent injection. No such significant difference was found between pigs that received the contrast agent as a bolus injection compared to infusion. Conclusion:Dobutamine stress increases uptake of manganese ions in the myocardium. This increase was independent of whether the contrast agent was administered as a bolus injection or as an infusion.

Contrast enhancement of manganese‐hydroxypropyl‐tetraacetic acid, an MR contrast agent with potential for detecting differences in myocardial blood flow

“…Many earlier studies of manganese-enhanced MRI focused on MnCl 2 and MnDPDP, and showed that in rabbit, rat, dog, and pig hearts ⌬R1 increased with the concentration of the administered contrast agent (7,20 -22). The enhancement pattern we observed for MnHPTA is similar to that reported for MnCl 2 in earlier studies that used the same model employed in the present study (20,22). On the other hand, studies in dogs and rats using other models showed a more stable contrast enhancement over the first 30 minutes after injection (23,24).…”

“…Quantitatively, MnHPTA 15mol/kg increased R1 to a level similar to that observed in a previous study (22) This difference was also observed in a study of mice, in which a comparison of infusion of MnCl 2 at rest and during dobutamine-induced stress revealed a considerable difference in signal intensity (28). For MnHPTA this difference was found only after the 25 mol/kg injection.…”

KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart

“…Male (n ϭ 4 each) and female (n ϭ 4 each) Kir6.2-KO mice or WT counterparts were anesthetized via intraperitoneal administration of 2,2,2-tribromoethanol (Avertin) at a dose of 250 mg/kg body wt. Under sterile conditions, a heparinized 10-l total volume polyethylene-10 catheter was introduced into the right internal jugular and sutured in place for infusion of the Mn 2ϩ and dobutamine solutions, used for tracing calcium influx and stress induction, respectively (13,19,20,35,56). Anesthesia was then maintained with Ͻ1% inhaled isoflurane to allow for a constant and controllable level of anesthesia and heart rate during the manganeseenhanced cardiac MRI procedure.…”

“…Manganese-induced enhancement of the magnetic resonance cardiac signal is indicative of calcium influx into the heart (13,19,20,35). Accordingly, manganese-enhanced cardiac MRI was employed to probe the consequence of K ATP channel deletion on calcium loading under stress in vivo.…”

“…Under dobutamine challenge (56), in vivo manganese-enhanced cardiac magnetic resonance imaging (13,19,20,35) captured excessive calcium accumulation in mice deficient in K ATP channels, precipitating poor recovery. Deficit in K ATP channels translated into compromised function in the stunned heart, with the knockout phenotype rescued by targeting alternative pathways of calcium handling.…”