Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats

Waller, Christiane; Engelhorn, Tobias; Hiller, K. H.; Heusch, Gerd; Ertl, Georg; Bauer, Wolfgang R.; Schulz, Rainer

doi:10.1152/ajpheart.01060.2004

Cited by 13 publications

(15 citation statements)

References 30 publications

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“…(Table 1). We applied all currently used semiquantitative correction methods for MBF (8,26,40) in additional animals, and tissue perfusion in the infarct in MSC-treated animals was always increased relative to control and placebo animals at week 1 (P Ͻ 0.01 and P Ͻ 0.001; Fig. 5).…”

Section: Myocardial Blood Flowmentioning

confidence: 99%

Early improvement in cardiac tissue perfusion due to mesenchymal stem cells

Schuleri¹,

Amado²,

Boyle³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

148

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The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, approximately 15 injections) (n = 10), placebo (n = 6), or no intervention (n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals [0.17 +/- 0.03, 0.09 +/- 0.01, and 0.08 +/- 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated]. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment.

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Section: Myocardial Blood Flowmentioning

confidence: 99%

Early improvement in cardiac tissue perfusion due to mesenchymal stem cells

Schuleri¹,

Amado²,

Boyle³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

148

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“…Furthermore, cardiac motion itself restricts data acquisition to end diastole. To overcome these challenges, rapid SNAPSHOT-FLASH IR imaging (SNAP-IR) has been implemented by single laboratories (18,19,22). In this technique, each voxel is filled with the T1 of the underlying tissue (6) and, therefore, directly and inversely represents the actual Gd concentration.…”

mentioning

confidence: 99%

Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI

Bohl

Lygate²,

Barnes³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement MRI (3D-LGE). Myocardial T1 relaxation was quantified at 9.4 Tesla in five mice, and reproducibility was tested by repeat imaging after 5 days. In a separate set of healthy and infarcted mice (n = 8 of each), continuous T1 measurements were made following intravenous or intraperitoneal injection of a contrast agent (0.5 micromol/g gadolinium-diethylenetriamine pentaacetic acid). The time course of T1 contrast development between viable and nonviable myocardium was thereby determined, with optimal postinjection imaging windows and inversion times identified. Infarct sizes were quantified using 3D-LGE and compared with triphenyltetrazolium chloride histology on day 1 after infarction (n = 8). Baseline myocardial T1 was highly reproducible: the mean value was 952 +/- 41 ms. T1 contrast peaked earlier after intravenous injection than with intraperitoneal injection; however, contrast between viable and nonviable myocardium was comparable for both routes (P = 0.31), with adequate contrast remaining for at least 60 min postinjection. Excellent correlation was obtained between infarct sizes derived from 3D-LGE and histology (r = 0.91, P = 0.002), and Bland-Altman analysis indicated good agreement free from systematic bias. We have validated an improved 3D MRI method to noninvasively quantify infarct size in mice with unsurpassed spatial resolution and tissue contrast. This method is particularly suited to studies requiring early quantification of initial infarct size, for example, to measure damage before intervention with stem cells.

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“…Serial measurements of perfusion in rats after myocardial infarction of intermediate size revealed a continuous decrease in the residual myocardium perfusion under baseline conditions and after maximum vasodilatation [23]. It is a well known fact that residual myocardium develops a compensatory hypertrophy after infarction.…”

Section: Applications To Assess Pathophysiology Of the Cardiovascularmentioning

confidence: 92%

“…This technique has been established and validated in the isolated rat heart [18,19], and in the intact rat [20][21][22][23][24] and mice heart (Fig. 6) [25,26].…”

Section: Measurement Of Myocardial Blood Supplymentioning

confidence: 99%

“…In addition, the rat model of coronary stenosis has been helpful to develop and validate novel MRI methods, such as spin labelling perfusion [23] or spectroscopic imaging [33]. On the other hand, application of these methods helped to better understand pathophysiology and metabolism in coronary heart disease (Fig.…”

Section: Applications To Assess Pathophysiology Of the Cardiovascularmentioning

confidence: 99%

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Recent Advances in Small Animal Cardiac Magnetic Resonance Imaging

Nahrendorf¹,

Bauer²

2006

CCR

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Small animal models of heart failure have added invaluable information to advance diagnosis, pathophysiology and treatment of patients with heart failure, a growing epidemic in the western world. During the last decade, advances in small animal magnetic resonance imaging have contributed to this accumulating body of knowledge.In the review we give an overview about imaging techniques, their application to heart failure models in rats and mice, with focusing on providing practical information which will aid readers to acknowledge the opportunities offered by small animal MRI. We aim to provide this information as a useful guidance for developing imaging strategies and experimental protocols. In addition, theoretical background with respect to physics of imaging and pathophysiology of disease will be discussed. Techniques like cine, spin labeling perfusion, determination of regional blood volume by usage of intravascular contrast agents, myocardial motion encoding by phase mapping, coronary angiography, spectroscopic imaging, assessment of viability by late enhancement techniques will be described with specific applications in mind, such as phenotyping of the creatine kinase knock out mouse and assessment of myocardial mechanics and perfusion during remodeling after myocardial infarction.

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Impaired resting perfusion in viable myocardium distal to chronic coronary stenosis in rats

Cited by 13 publications

References 30 publications

Early improvement in cardiac tissue perfusion due to mesenchymal stem cells

Early improvement in cardiac tissue perfusion due to mesenchymal stem cells

Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI

Recent Advances in Small Animal Cardiac Magnetic Resonance Imaging

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