Assessment of Myocardial Infarction and Postinfarction Scar Remodeling With an Elastin-Specific Magnetic Resonance Agent

Abstract

Background-To prospectively evaluate an elastin-specific MR contrast agent (ESMA) for in vivo targeting of elastic fibers in myocardial infarction (MI) and postinfarction scar remodeling. Methods and Results-MI was induced in C57BL/6J mice (n=40) by permanent ligation of the left anterior descending coronary artery. MRI was performed at 7 and 21 days after MI. The merits of gadolinium-based ESMA (Gd-ESMA) were compared with gadopentetic acid (Gd-DTPA) for infarct size determination, contrast-to-noise ratio (CNR), and enhancement kinetics. Specific binding in vivo was evaluated by blocking the molecular target using nonparamagnetic lanthanum-ESMA. In vivo imaging results were confirmed by postmortem triphenyltetrazolium chloride staining, elastica van Gieson staining, and Western blotting. Delayed enhancement MRI revealed prolonged enhancement of Gd-ESMA in the postischemic scar compared with Gd-DTPA. Infarct size measurements showed good agreement between Gd-ESMA and Gd-DTPA and were confirmed by ex vivo triphenyltetrazolium chloride staining. Preinjection of the blocking lanthanum-ESMA resulted in significantly lower CNR of Gd-ESMA at the infarct site (P=0.0019). Although no significant differences in CNR were observed between delayed enhancement imaging and Gd-DTPA between days 7 and 21 (1.8± versus 3.8; P=ns), Gd-ESMA showed markedly higher CNR on day 21 after MI (14.1 versus 4.9; P=0.0032), which correlated with increased synthesis of tropoelastin detected by Western blot analysis and histology. Higher CNR values for Gd-ESMA further correlated with improved ejection fraction of the mice on day 21 after MI. Conclusions-Gd

Biomechanics of Cardiac Function

“…Given the abundance of myocytes in the myocardial tissue, titin is considered to be the primary determinant of the passive mechanical properties of the healthy LV under low to moderate deformations (76). Interestingly, titin has many isoforms with some variants being significantly less stiff than others, and differences in the expression of these isoforms could play a role the development of diastolic dysfunction and heart failure (208). Further mutations of the titin gene have been associated with a number of various cardiomyopathies (117).…”

“…Elastic fibers, as their name would indicate have an elastic stress-strain behavior, similar to the mechanical properties of titin, which is much more abundant in the healthy myocardium (48, 118). Studies of elastin in the healthy myocardium remain very limited, however elastin is becoming a more active subject of study in left ventricular remodeling and in regenerative medicine which will be discussed later in this review (48, 108, 130, 208). …”

Left ventricular remodeling in patients with right ventricular myocardial infarction

“…Некроз мышечных волокон сопровожда-ется дилатацией полости ЛЖ, перераспределением регионального напряжения на стенки ЛЖ, компенса-торной гиперкинетической активностью здоровых уча-стков миокарда, направленной на сохранение общей фракции выброса и фракции укорочения мышечных во-локон ЛЖ [13]. Эти изменения структуры стенки ЛЖ, объемов и формы (геометрии) камер сердца часто пред-шествуют клиническому проявлению синдрома сер-дечной недостаточности, являются предвестниками декомпенсации сердечной деятельности и отрица-тельно влияют на качество жизни и выживаемость больных [14].…”

Spatially Resolved Quantification of Gadolinium(III)‐Based Magnetic Resonance Agents in Tissue by MALDI Imaging Mass Spectrometry after In Vivo MRI

“…We demonstrated tissue dynamics over time of ac ollagentargeted MRI contrast agent (Gadofluorine M) in different tissue regions of the diseased mouse heart. [10] Them ouse was sacrificed one hour after administration of Gadofluorine M. Theh eart was excised and immediately snap-frozen in liquid nitrogen. [7,8] The prolonged in vivo enhancement kinetics of the agent was the primary rationale for evaluating this agent further by MALDI imaging.T he analytical MALDI imaging setting for Gadofluorine Mwas optimized using ex vivo treated tissue according to ap reviously published protocol.…”

“…[10,12,13] As illustrated in Figure 3, three clinically approved, as well as one experimental paramagnetic MRI contrast agents,w ere evaluated for possible detection by MALDI imaging.G adopentetate dimeglumine (Gd-DTPA, Bayer Healthcare,Berlin, Germany) is the most widely applied contrast agent in clinical practice.A fter intravenous administration Gd-DTPAq uickly extravasates from the vasculature by diffusion and accumulates within the extracellular space,from which it is eliminated at ahalf-life of approximately 90 minutes.G adobutrol (Gadovist, Bayer Healthcare,B erlin, Germany) is am acrocyclic complex with increased thermodynamic stability as well as increased r1 and r2 relaxivity compared to Gd-DTPA. More and more,t argeted molecular contrast agents are being evaluated to study specific cellular and molecular processes in vivo both in health and disease.…”