Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat

Nahrendorf, Matthias; Hiller, K. H.; Greiser, Andreas; Köhler, Sascha; Neuberger, Thomas; Hu, Kai; Waller, Christiane; Albrecht, Matthias; Neubauer, Stefan; Haase, Axel; Ertl, Georg; Bauer, Wolfgang R.

doi:10.1152/ajpheart.00233.2003

Cited by 23 publications

(21 citation statements)

References 36 publications

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“…The small animal models of chronic coronary artery stenosis in rats and mice are widely used as experimental models of acute and chronic ischemia (7,9,20,21). As in previous studies in large animals and humans (13,14,17,22), blood flow to viable portions of poststenotic myocardium in rodents is reduced, as indicated in the present study.…”

Section: Discussionsupporting

confidence: 59%

“…Alterations in global and regional LV function are therefore secondary to both patchy fibrosis and reduced resting perfusion. ischemic cardiomyopathy; necrosis IN RATS WITH A CHRONIC coronary artery stenosis, regional and global left ventricular (LV) function is reduced (20), and the poststenotic myocardium is characterized by apoptosis and reparative fibrosis with normal myofibrillar ATPase activity (1,8). Capasso et al (8) observed that within the first 3 days following the induction of an ϳ60% diameter stenosis of a coronary artery, blood flow reserve was reduced whereas resting blood flow was normal in the poststenotic myocardium as measured using microspheres.…”

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confidence: 99%

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

Waller¹,

Engelhorn²,

Hiller³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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The aim of the present study was to compare regional myocardial blood flow (RMBF) and function (F) in poststenotic myocardium by using magnetic resonance imaging (MRI) and to compare MRI blood flow changes to histological alterations to assess whether RMBF in the viable poststenotic tissue remains normal. MRI was performed in 11 anesthetized Wistar rats with 2-wk stenosis of the left coronary artery. Postmortem, the extent of fibrotic tissue was quantified. Poststenotic RMBF was significantly reduced to 2.21 Ϯ 0.30 ml ⅐ g Ϫ1 ⅐ min Ϫ1 compared with RMBF in the remote myocardium (4.05 Ϯ 0.50 ml ⅐ g Ϫ1 ⅐ min Ϫ1 ). A significant relationship between the poststenotic RMBF (%remote area) and the poststenotic F (%remote myocardium) was calculated (r ϭ 0.61, P Ͻ 0.05). Assuming perfusion in scar tissue to be 32 Ϯ 5% of perfusion of remote myocardium, as measured in five additional rats, and that in remote myocardium to be 114 Ϯ 25% of that in normal myocardium, as assessed in five sham rats, the calculated perfusion in partially fibrotic tissue samples (35.7 Ϯ 5.2% of analyzed area) was 2.88 Ϯ 0.18 ml ⅐ g Ϫ1 ⅐ min Ϫ1 , whereas measured MRI perfusion was only 1.86 Ϯ 0.24 ml ⅐ g Ϫ1 ⅐ min Ϫ1 (P Ͻ 0.05). These results indicate that resting perfusion in viable poststenotic myocardium is moderately reduced. Alterations in global and regional LV function are therefore secondary to both patchy fibrosis and reduced resting perfusion.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

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

Waller¹,

Engelhorn²,

Hiller³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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“…It has been impractical to perform 31 P-MRSI at low-field clinical scanners with adequate resolution and scan time. Preclinical 31 P and other hetero-nuclei MRSI studies are commonly performed at high fields for SNR gain (53)(54)(55). However, the requirement of high spatial resolution for small animal imaging still renders 31 P-MRSI challenging.…”

Section: Historical Perspectivementioning

confidence: 99%

Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

Liu

2017

Quant. Imaging Med. Surg.

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Many human diseases are caused by an imbalance between energy production and demand.Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) provide the unique opportunity for in vivo assessment of several fundamental events in tissue metabolism without the use of ionizing radiation. Of particular interest, phosphate metabolites that are involved in ATP generation and utilization can be quantified noninvasively by phosphorous-31 ( 31 P) MRS/MRI. Furthermore, 31 P magnetization transfer (MT) techniques allow in vivo measurement of metabolic fluxes via creatine kinase (CK) and ATP synthase. However, a major impediment for the clinical applications of 31 P-MRS/MRI is the prohibitively long acquisition time and/or the low spatial resolution that are necessary to achieve adequate signal-to-noise ratio. P-MRS/MRI techniques. Applications of these techniques to the investigation of a specific physiology/pathology will be discussed without detailed description. Interested readers are referred to recent review articles on the applications of 31 P-MRS/MRI in metabolic characterization of skeletal muscle (10-12), heart (13), brain (14), and liver (11), as well as in diseases such as cancer (15), heart failure (16), and obesity and diabetes (17,18). Historical perspectiveThe use of 31 P-MRS for metabolic investigations dates back to 1960. Cohn and Hughes were the first to obtain a high-resolution 31 P spectrum of a solution of ATP (19). In addition, they also observed a dependence of the chemical shifts of the phosphorus nuclei of ATP on the pH of the solution. In parallel to the early development of MRI methods by Lauterbur (20), the entire 1970s also witnessed the rapid advance of 31 P-MRS in metabolic investigation of a broad range of biological systems. In 1973, Moon and Richards performed the first 31 P-MRS study that measured intracellular pH in human red blood cells (21). In the following year, Henderson and colleagues obtained the first 31 P spectrum of ATP from human red blood cells (22). At the same time, the Oxford team led by Radda performed the first experiment to acquire 31 P spectra from an intact organ, i.e., the excised and superfused muscle of rat hindlimb (23). The first in vivo 31 P-MRS study was performed on mouse brain by Chance et al. (24). Within the short span of one decade, organelles including mitochondria (25,26) and chromaffin granules (27), cells including Escherichia coli (28), yeast (29), and hepatocytes (30), and organs including skeletal muscle (31,32), heart (33-35), brain (36), kidney (37), and liver (38,39) have all been studied using 31 P-MRS.It is worth noting that most of these organ studies were performed on excised organs to avoid the need for spatial localization. Although Lauterbur has demonstrated the feasibility of imaging water protons (20), it was considered impractical for 31 P imaging of living systems because of the low sensitivity and difficulties with spectral resolution.The 1980s began with the publication of two important studies that aimed a...

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“…However, because the normal pattern of inotropic reserve can be greatly altered during severe LV dysfunction, such an observation in this context is unlikely. Experimental data from MRI have revealed a blunted inotropic response in the remote myocardium of rats with drastic drop of cardiac output due to chronic coronary stenosis (122). In patients with severe LV dysfunction, Skopicki et al (151) reported that an abnormal response to dobutamine frequently occurred in regions that contracted normally, were classified as normal by PET, with a normal hyperemic response to adenosine, and were fed by a patent coronary vessel.…”

Section: Imaging Diagnosis Of Stunning In Severe Cadmentioning

confidence: 99%

“…Interestingly, in both settings, functional impairment has been reported in the remote myocardium of dilated LV presenting geometrical alteration (16,96,122). Whether increased wall stress causes this functional impairment remains unknown.…”

Section: Myocardial Wall Stressmentioning

confidence: 99%

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

Mazzadi

André‐Fouët²,

Costes³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Croisille, Didier Revel, and Marc F. Janier. Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning. Am J Physiol Heart Circ Physiol 291: H2570 -H2582, 2006. First published July 21, 2006 doi:10.1152/ajpheart.01249.2005.-Patients with severe chronic coronary artery disease (CAD) exhibit a highly altered myocardial pattern of perfusion, metabolism, and mechanical performance. In this context, the diagnosis of stunning remains elusive not only because of methodological and logistic considerations, but also because of the pathophysiological characteristics of the myocardium of these patients. In addition, a number of alternative pathophysiological mechanisms may act by mimicking the functional manifestations usually attributed to stunning. The present review describes three mechanisms that could theoretically lead to reversible mechanical dysfunction in these patients: myocardial wall stress, the tethering effect, and myocardial expression and release of auto-and paracrine agents. Attention is focused on the role of these mechanisms in scintigraphically "normal" regions (i.e., regions usually showing normal perfusion, glucose metabolism, and cellular integrity as assessed by nuclear imaging techniques), in which stunning is usually considered, but these mechanisms could also operate throughout the viable myocardium. We hypothesize that reversion of these three mechanisms could partially explain the unexpected functional benefit after reperfusion recently highlighted by high-spatial-resolution imaging techniques. stunned myocardium; hibernating myocardium; inotropic reserve; cardiac imaging; myocardial wall stress; ventricular remodeling SUMMARY OF CLINICAL PROBLEMIN RECENT YEARS, WIDESPREAD utilization of noninvasive cardiac imaging methods has greatly improved the synergy between clinical and basic investigation of cardiac ischemic pathophysiology. Thus imaging methods have shown that the reversible left ventricular (LV) dysfunction arising from brief coronary occlusion and reflow (myocardial stunning), first described in animal models (80), occurs in humans. Two major hypotheses explain this phenomenon: 1) the oxyradical hypothesis, which proposes that oxidant stress impairs LV function (18), and 2) the calcium hypothesis, which postulates that stunning results from disturbed myocyte calcium homeostasis (98). On the other hand, the hibernating myocardium (136, 137) was first discovered by imaging methods in humans, and it was originally defined as "resting LV dysfunction due to reduced coronary blood flow that can be partially or completely reversed by myocardial revascularization and/or by reducing myocardial oxygen demand" (136). The concept was refined when ultrastructural investigations showed a distinctive morphology for hibernating myocardium, generally without necrosis, but with loss of sarcomeres and myofibrils (suggesting a "dedifferentiation" process toward an embryonic phenotype), with loss of mitochondria and increased glycogen storage (9,19,27,162)...

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Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat

Cited by 23 publications

References 36 publications

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

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

Assessing tissue metabolism by phosphorous-31 magnetic resonance spectroscopy and imaging: a methodology review

Mechanisms leading to reversible mechanical dysfunction in severe CAD: alternatives to myocardial stunning

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