Serial Magnetic Resonance Imaging of Microvascular Remodeling in the Infarcted Rat Heart

Waller, Christiane; Hiller, K. H.; Kahler, Elke; Hu, Kai; Nahrendorf, Matthias; Voll, Sabine; Haase, Axel; Ertl, Georg; Bauer, Wolfgang R.

doi:10.1161/01.cir.103.11.1564

Cited by 50 publications

(40 citation statements)

References 35 publications

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“…This represents the remodeling after MI and the presented results are consistent with findings in rats after MI (35). After MI, the remote myocardium hypertrophies (36).…”

Section: Discussionsupporting

confidence: 91%

In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging

Streif¹,

Nahrendorf²,

Hiller³

et al. 2005

Magnetic Resonance in Med

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The absolute perfusion and the intracapillary or regional blood volume (RBV) in murine myocardium were assessed in vivo by spin labeling magnetic resonance imaging. Pixel-based perfusion and RBV maps were calculated at a pixel resolution of 469 ؋ 469 m and a slice thickness of 2 mm. The T 1 imaging module was a segmented inversion recovery snapshot fast low angle shot sequence with velocity compensation in all three gradient directions. The group average myocardial perfusion at baseline was determined to be 701 ؎ 53 mL (100 g ⅐ min) ؊1 for anesthesia with isoflurane (N ‫؍‬ 11) at a mean heart rate (HR) of 455 ؎ 10 beats per minute (bpm). This value is in good agreement with perfusion values determined by invasive microspheres examinations. For i.v. administration of the anesthetic Propofol, the baseline perfusion decreased to 383 ؎ 40 mL (100 g ⅐ min) ؊1 (N ‫؍‬ 17, P < 0.05 versus. isoflurane) at a mean heart rate of 261 ؎ 13 bpm (P < 0.05 versus isoflurane). In addition, six mice with myocardial infarction were studied under isoflurane anesthesia (HR 397 ؎ 7 bpm). The perfusion maps showed a clear decrease of the perfusion in the infarcted area. The perfusion in the remote myocardium decreased significantly to 476 ؎ 81 mL (100 g ⅐ min) ؊1 (P < 0.05 versus sham). Regarding the regional blood volume, a mean value of 11.8 ؎ 0.8 vol % was determined for healthy murine myocardium under anesthesia with Propofol (N ‫؍‬ 4, HR 233 ؎ 17 bpm). In total, the presented techniques provide noninvasive in vivo assessment of the perfusion and the regional blood volume in the murine myocardium for the first time and seem to be promising tools for the characterization of mouse models in cardiovascular research. Over the past decade, the mouse animal model has become an essential part of medical basic research. This is due to the high degree of similarity between the mouse and the human genomes of about 97% (1) and the resulting high relevance of mouse animal studies for human basic research. Regarding cardiovascular research, magnetic resonance imaging (MRI) provides noninvasive and accurate assessment of cardiac structure and function (2). Since the viability and the capability of the myocardium are strongly influenced by its microcirculation, a full characterization of the myocardium requires a quantification of parameters such as the perfusion and the intracapillary or regional blood volume (RBV). In particular, perfusion is of paramount importance as a physiologic parameter, since it strongly determines the function of organs and the severity of many diseases.Heart diseases involving ventricular dysfunction and hypertrophy show significant alterations of the myocardial perfusion and transgenic mouse models may be well suited to elucidate the underlying fundamental mechanisms.For the assessment of cardiac perfusion in mice, only a few methods have been presented to date. One possible approach is the quantification of the coronary flow in the isolated mouse heart by ultrasonic flow probes (3). The injection of labeled microsphe...

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“…This represents the remodeling after MI and the presented results are consistent with findings in rats after MI (35). After MI, the remote myocardium hypertrophies (36).…”

Section: Discussionsupporting

confidence: 91%

In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging

Streif¹,

Nahrendorf²,

Hiller³

et al. 2005

Magnetic Resonance in Med

Self Cite

View full text Add to dashboard Cite

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“…Thus, whereas the myocytes in these hearts undergo hypertrophy, the number of capillaries does not increase, and a demand/supply mismatch may ensue. In rats, a reduction in capillary density has also been described in the hypertrophied areas of remodeled myocardium (1) and has been demonstrated to result in diminished perfusion values (24). This reduction in perfusion may place the myocardium remote from the infarct under even further stress and contribute to the evolution of heart failure.…”

Section: Discussionmentioning

confidence: 96%

Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics

Nahrendorf

Streif²,

Hiller³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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, and Wolfgang R. Bauer. Multimodal functional cardiac MRI in creatine kinasedeficient mice reveals subtle abnormalities in myocardial perfusion and mechanics. Am J Physiol Heart Circ Physiol 290: H2516-H2521, 2006. First published January 13, 2006; doi:10.1152/ajpheart.01038.2005.-A decrease in the supply of ATP from the creatine kinase (CK) system is thought to contribute to the evolution of heart failure. However, previous studies on mice with a combined knockout of the mitochondrial and cytosolic CK (CK Ϫ/Ϫ ) have not revealed overt left ventricular dysfunction. The aim of this study was to employ novel MRI techniques to measure maximal myocardial velocity (Vmax) and myocardial perfusion and thus determine whether abnormalities in the myocardial phenotype existed in CK Ϫ/Ϫ mice, both at baseline and 4 wk after myocardial infarction (MI Ϫ/Ϫ MI, 3.71 Ϯ 0.57 ml/g ⅐ min, P ϭ NS, P Ͻ 0.05 vs. baseline), paralleled by a significantly reduced capillary density (histology). In conclusion, myocardial function in transgenic mice may appear normal when only gross indexes of performance such as EF are assessed. However, the use of a combination of novel MRI techniques to measure myocardial perfusion and mechanics allowed the abnormalities in the CK Ϫ/Ϫ phenotype to be detected. The myocardium in CK-deficient mice is characterized by reduced perfusion and reduced maximal contraction velocity, suggesting that the myocardial hypertrophy seen in these mice cannot fully compensate for the absence of the CK system. magnetic resonance imaging; contractility; myocardial infarction CHANGES IN myocardial energetics, including reduced levels of phosphocreatine, creatine kinase (CK) (10, 16), and ATP (20), have been documented in the failing heart. However, whether these alterations in myocardial energetics are a causal mechanism contributing to left ventricular (LV) remodeling and dysfunction or an adaptive phenomenon has yet to be resolved. Recently, our group reported that deletion of the CK enzyme system [double knockout of the mitochondrial and cytosolic CK (CK Ϫ/Ϫ )] leads to adaptive changes of the murine heart, consisting of LV hypertrophy and mild dilatation of the LV. However, cardiac output and LV ejection fraction remained normal in these mice (15). Furthermore, when CK Ϫ/Ϫ mice were examined 4 wk after the induction of myocardial infarction (MI), no evidence of adverse LV remodeling was seen (15). Therefore, the aim of the current study was to determine whether the use of novel techniques in mouse cardiac MRI, such as perfusion imaging and the imaging of myocardial mechanics, would allow subtle abnormalities of the myocardial phenotype to be detected.A phase-contrast MRI pulse sequence, recently developed by our group (21) to measure myocardial contraction velocity and mechanics in mice, was used in this study. In addition, a second novel MR technique to quantify myocardial perfusion, which has also recently been modified to work in the small and rapidly beating mouse heart (12, 22), was employed to assess myocardial p...

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“…In recent years the mouse has become the animal of choice in studies of many aspects of cardiovascular diseases, which is largely due to the large number of transgenic and knockout mice that has become available. The significant added value of MRI for studying murine models of cardiovascular disease processes, including atherosclerosis [19][20][21][22][23], cardiac hypertrophy [24], and myocardial infarction [25][26][27][28][29][30], is well established.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging of regional cardiac function in the mouse

Heijman

Strijkers

Habets

et al. 2004

MAGMA

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In this paper we introduce an improved harmonic phase (HARP) analysis for complementary spatial modulation of magnetization (CSPAMM) tagging of the mouse left ventricular wall, which enables the determination of regional displacement fields with the same resolution as the corresponding CINE anatomical images. CINE MRI was used to measure global function, such as the ejection fraction. The method was tested on two healthy mouse hearts and two mouse hearts with a myocardial infarction, which was induced by a ligation of the left anterior descending coronary artery. We show that the regional displacement fields can be determined. The mean circumferential strain for the left ventricular wall of one of the healthy mice was −0.09 ± 0.04 (mean ± standard deviation), while for one of the infarcted mouse hearts strains of −0.02 ± 0.02 and −0.10 ± 0.03 were found in the infarcted and remote regions, respectively.

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Serial Magnetic Resonance Imaging of Microvascular Remodeling in the Infarcted Rat Heart

Cited by 50 publications

References 35 publications

In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging

In vivo assessment of absolute perfusion and intracapillary blood volume in the murine myocardium by spin labeling magnetic resonance imaging

Multimodal functional cardiac MRI in creatine kinase-deficient mice reveals subtle abnormalities in myocardial perfusion and mechanics

Magnetic resonance imaging of regional cardiac function in the mouse

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