Mr Imaging of Acute Myocardial Infarction in Pigs Using Gd-DTPA-Labeled Dextran

Wikström, Mats; Martinussen, H. J.; Wikström, Gerhard; Ericsson, Anders; Nyman, Rickard; Waldenström, Anders; Hemmingsson, Anders

doi:10.1080/02841859209173183

Cited by 9 publications

(9 citation statements)

References 18 publications

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“…Albumin conjugated with diethylenetriaminepentaacetic acid (DTPA) [albumin‐(DTPA‐Gd) 30‐34 ], originally described by Ogan, et al (16), was initially studied. The other types of macromolecular contrast agents have contained artificially synthesized polyamines (17), were based on dextrans (18–20), or were liposome‐based (21) conjugates using Gd(III) chelates (DTPA derivatives or 1,4,7,10‐tetraazacyclododecane tetraacetic acid [DOTA] derivatives). Although polylysine has been mainly used for the core of blood‐pool contrast agents (17, 22, 23), starburst PAMAM dendrimers have been proposed recently as an alternative to polylysines (7, 8, 24).…”

Section: Discussionmentioning

confidence: 99%

Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents

Kobayashi

Kawamoto

Saga

et al. 2001

Magnetic Resonance Imaging

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Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd) 2 x؉2 were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd) 256 . In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd) 512 , G8D-(1B4M-Gd) 1024 , and G9D-(1B4M-Gd) 2048 was shown compared to G6D-(1B4M-Gd) 256 (P < 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd) 1024 and G9D-(1B4M-Gd) 2048 in the liver compared to G6D-(1B4M-Gd) 256 and G7D-(1B4M-Gd) 512 (P < 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D-(1B4M-Gd) 512 (P < 0.01). The normal and intratumoral fine vessels of approximately 100 m diameter were visualized in normal or tumor-bearing mice by high resolution three-dimensional-micro-MR angiographs with G7D-(1B4M-Gd) 512 and G8D-(1B4M-Gd) 1024 with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimerbased MRI contrast agents.

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Section: Discussionmentioning

confidence: 99%

Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents

Kobayashi

Kawamoto

Saga

et al. 2001

Magnetic Resonance Imaging

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“…TTC forms a red precipitate in viable tissue, and myocardium that stained red was defined as TTC positive and therefore as viable. Myocardium that did not stain red appeared pale yellow under incandescent light and was defined as TTC negative and therefore as infarcted myocardium (35). The area of infarcted tissue was defined as the area of MI.…”

Section: Quantification Of Area At Risk and Myocardial Infarctionmentioning

confidence: 99%

Proteasome inhibition ablates activation of NF-κB in myocardial reperfusion and reduces reperfusion injury

Pye¹,

Ardeshirpour²,

McCain³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

159

120

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Both acute coronary occlusion and reperfusion of an infarct-related artery lead to significant myocardial cell death. Recent evidence has been presented that activation of the transcription factor nuclear factor-κB (NF-κB) plays a critical role in reperfusion injury. NF-κB is usually bound to its inhibitor, IκB, and classic activation of NF-κB occurs when the 20S proteasome degrades IκB that has been phosphorylated and ubiquitinated. In this study, activation of NF-κB was inhibited by systemic administration of a 20S proteasome inhibitor (PS-519) in a porcine model of myocardial reperfusion injury. The experimental protocol induced myocardial ischemia in the distribution of the left anterior descending coronary artery for 1 h with subsequent reperfusion for 3 h. A single systemic treatment with PS-519 reduced 20S proteasome activity; blocked activation of NF-κB induced by reperfusion; reduced creatine kinase, creatine kinase-muscle-brain fraction, and troponin I release from the myocardium; preserved regional myocardial function measured by segmental shortening; significantly reduced the size of myocardial infarction; and exhibited no acute toxicity. These data show that myocardial reperfusion injury can be inhibited by using proteasome inhibitors, which likely function through the inhibition of NF-κB activation.

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“…Macromolecular contrast agents designed for intravascular distribution in normal tissues, such as albumin-(Gd-DTPA)20 (26), dextran-(Gd-DTPA),, (25) and Gd-DTPA polylysine (1 5), as well as complexes formed of manganese with biologic substances such as pyridoxal phosphate (1 1) cause a prolonged signal enhancement of nonischemic myocardium.…”

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confidence: 99%

Double-Contrast Enhanced MR Imaging of Myocardial Infarction in the Pig

et al. 1993

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Myocardial infarction was induced by ligating a diagonal branch of the left anterior descending artery in 18 pigs. All pigs were sacrificed 6 h after the occlusion. Dysprosium diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA, 1 .O mmol/kg) was administered i.v. to 6 pigs, starting 3 min before sacrifice (injection time approximately 1 min). In a second group of 6 pigs, a double-contrast technique was used, consisting of an i.v. injection of gadolinium-DTPA-BMA (0.4 mmol/kg) 2 h before sacrifice, followed by an i.v. injection of Dy-DTPA-BMA (1.0 mmol/kg) 3 min before sacrifice. Six additional pigs, subjected to 6 h of coronary artery occlusion without administration of contrast medium, served as controls. The hearts were excised and imaged with MR. In the control animals. the infarctions demonstrated an increased signal intensity in the proton density-and T2-weighted images. Administration of Dy-DTPA-BMA primarily improved infarct visualization in the proton density-and T2-weighted images, due to reduction of signal intensity in nonischemic myocardium. The double-contrast technique further improved infarct visualization in all sequences.

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Mr Imaging of Acute Myocardial Infarction in Pigs Using Gd-DTPA-Labeled Dextran

Cited by 9 publications

References 18 publications

Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents

Micro‐MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: Reference to pharmacokinetic properties of dendrimer‐based MR contrast agents

Proteasome inhibition ablates activation of NF-κB in myocardial reperfusion and reduces reperfusion injury

Double-Contrast Enhanced MR Imaging of Myocardial Infarction in the Pig

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