High-energy Phosphate Metabolism of the Myocardium in Normal Subjects and Patients with Various Cardiomyopathies. The study using ECG gated MR spectroscopy with a localization technique.

Masuda, Yoshiaki; Tateno, Yukio; Ikehira, Hiroo; Hashimoto, Takayuki; Shishido, Fumio; Sekiya, Masao; Imazeki, Yasuo; Imai, Hitoshi; Watanabe, Shotaro; Inagaki, Yoshiaki

doi:10.1253/jcj.56.620

Cited by 34 publications

(13 citation statements)

References 13 publications

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“…This pacing-gated 31 P NMR method may be useful for evaluating the efficiency of energy Circulation Journal Vol.66, January 2002 utilization of the myocardium in patients with ischemic heart disease, cardiac failure, and various cardiomyopathy. 27,28 …”

Section: Discussionmentioning

confidence: 99%

Cyclical Changes in High-Energy Phosphates During the Cardiac Cycle by Pacing-Gated 31P Nuclear Magnetic Resonance

Honda¹,

Tanaka

Akita³

et al. 2002

Circ J

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number of studies of myocardial energy metabolism using 31 P nuclear magnetic resonance (NMR) have been done on in vitro 1-4 and in vivo [5][6][7] hearts. Cyclical changes in the concentration of adenosine triphosphate (ATP), phosphocreatine (PCr), and inorganic phosphate (Pi) during the cardiac cycle have also been studied using the subject's blood pressure or electrocardiogram (ECG)-gated 31 P NMR techniques. Several studies have demonstrated that cyclical changes in ATP, PCr, and Pi arise in vitro [8][9][10] and in vivo 11 in rat hearts. However, some investigators have not observed any cyclical changes in energy-related phosphate levels in in vitro 12 and in vivo 5,13-15 hearts. Controversy remains regarding the presence of cyclical changes in energy-related phosphate levels. Hoh et al performed electrophoretic analyses in pyrophosphate gels of intact myosin of adult rat myocardium. 16 Their study revealed the presence of 3 distinct components in ventricular myosin (V1, V2, and V3) and an association between the distribution of these myosin components and its adenosine triphosphatase (ATPase) activity.We have developed a pacing-gated NMR technique that is triggered by pulses for cardiac pacing. 10 This is a suitable method for determining cyclical changes in energy-related phosphate compounds in the cardiac cycle because the heart rate and the RF pulse repetition time maintain a constant relationship with pacing. The purpose of the present study was to determine whether cyclical changes in energy-related phosphate levels arise during the cardiac cycle in isolated rat hearts and are affected by differences in myosin isozyme composition. To perform these studies, we used pacing-gated 31 P NMR spectroscopy and manipulated the cardiac workload. Hypo-and hyperthyroid rats, in which myocardial contractility and myocardial energy use should differ as a result of varying myosin isozyme composition, were used in the studies. Methods AnimalsThe experiments were performed on hearts removed from 8-week-old male Wistar rats of the following groups: (1) normal rats (n=10); (2) hypothyroid rats (n=10), who had received 0.8 mg/ml 6-n-propyl-2-thiouracil (PTU; Sigma, St Louis, MO, USA) in drinking water for 21 days, 17 and (3) hyperthyroid rats (n=5), who had received daily intraperitoneal injections of 500 g/kg body weight 3,5,3'-triiodo-L-thyronine (T3; Sigma) for 5 days. 18 Heart PreparationRats were anesthetized intraperitoneally with pentobarbital (Nembutal 20-25 mg/100 g of body weight). The heart was rapidly excised and immersed in the buffer. The aorta was dissected free and mounted onto a Teflon cannula attached to a perfusion apparatus. The isolated, perfused rat heart was suspended in an NMR tube with an outer diameter measuring 15 mm. The heart was perfused in the Langendorff mode under isovolumic conditions at a constant temperature of 37°C and a constant hydrostatic perfusion pressure of 100 cmH2O. We used a modified KrebsHenseleit buffer solution containing 118.0 mmol/L NaCl, 4.7 Whether cyclical changes in e...

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Section: Discussionmentioning

confidence: 99%

Cyclical Changes in High-Energy Phosphates During the Cardiac Cycle by Pacing-Gated 31P Nuclear Magnetic Resonance

Honda¹,

Tanaka

Akita³

et al. 2002

Circ J

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“…39 Because CK is relatively abundant even in the failing heart, 25,28 -32,38,40 a lower total creatine pool means that [PCr] must also be lower. 31 P NMR studies in the early 1990s by several groups [41][42][43][44] showed that [PCr]/[ATP] is lower in dilated cardiomyopathy and heart failure. In Figure 2, typical 31 P NMR spectra obtained noninvasively from normal and failing human hearts illustrate the changes in [ATP] and [PCr] that characterize the failing heart.…”

Section: Pcr and The Failing Heartmentioning

confidence: 99%

Is the Failing Heart Energy Starved?

Ingwall

Weiss

2004

Circulation Research

546

281

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Abstract-The requirement of chemical energy in the form of ATP to support systolic and diastolic work of the heart is absolute. Because of its central role in cardiac metabolism and performance, the subject of this review on energetics in the failing heart is ATP. We briefly review the basics of myocardial ATP metabolism and describe how this changes in the failing heart. We present an analysis of what is now known about the causes and consequences of these energetic changes and conclude by commenting on unsolved problems and opportunities for future basic and clinical research. Key Words: adenosine triphosphate Ⅲ phosphocreatine Ⅲ creatine kinase Ⅲ familial hypertrophic cardiomyopathy Ⅲ heart failure T he energy starvation hypothesis suggesting that the failing heart is energy-starved is decades old. 1,2 Because ATP is required for normal systolic and diastolic contractile performance, the idea that the failing heart is unable to meet the hemodynamic requirements of the body because there is not enough chemical energy available is logical. The hypothesis was initially set aside for several reasons. First, it was unclear whether the concentration of ATP ([ATP]) decreased. Second, it was reasoned that even if there were decreases in [ATP] in the failing heart, the remaining ATP should be sufficient to supply the ATP-requiring reactions in the myocyte. Third, our understanding of how ATP synthesis and use are regulated was remarkably incomplete. A good example of our ignorance about cardiac energetics was the use of inotropic agents to increase performance of the failing human heart. While increasing performance, these agents did so at great energetic cost and often resulted in increased, rather than decreased, heart failure mortality.There is now renewed interest in the energy-starvation hypothesis. 3,4 New biophysical tools such as nuclear magnetic resonance (NMR) spectroscopy, positron emission tomography (PET), and transgenesis using the mouse have allowed old questions to be revisited and new ones to be formulated. Combining old and new strategies to address the "energy starvation" hypothesis, we have learned much. We now know when and by how much [ATP] decreases in the hypertrophied and failing heart. We now know that despite increases in some ATP synthesizing pathways such as glycolysis, other pathways such as the creatine kinase (CK)-phosphocreatine (PCr) system decrease. Finally, we now have a better understanding of how the myocyte accomplishes the tasks of maintaining (near) normal ATP supply Original

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“…Some workers (34,52) report that the primary hypertrophic cardiomyopathy is more likely to result in an energy decline than the secondary hypertrophy, such as hypertension-induced LVH. In addition, a coexisting heart failure seems to increase the incidence of HEP abnormalities (21,47).…”

Section: Hypertrophic Model and Its Baseline Physiology/metabolismmentioning

confidence: 99%

Oxygen reperfusion is limited in the postischemic hypertrophic myocardium

Chung¹

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Chung, Youngran. Oxygen reperfusion is limited in the postischemic hypertrophic myocardium. Am J Physiol Heart Circ Physiol 290: H2075-H2084, 2006; doi:10.1152/ajpheart.00619.2005.-Studies have shown that hypertrophied hearts are unusually vulnerable to ischemia. Compromised O 2 supply has been postulated as a possible explanation for this phenomenon on the basis of elongated O 2 diffusion distance and altered coronary vasculature found in hypertrophied myocardium. To examine the postulate, perfused heart experiments followed the metabolic and functional responses of hypertrophic myocardium to ischemia.1 H/ 31 P NMR was used to measure cellular oxygenation and energy level during ischemia-reperfusion. The left ventricles from spontaneously hypertensive rats (SHR) were enlarged by 48%. With this moderate degree of hypertrophy, cellular O2 and energy levels were normal during baseline perfusion. After an ischemic episode, however, cellular O 2 was severely deprived in the SHR hearts compared with the normal hearts. Depressed postischemic O 2 reperfusion correlated well with depressed energetic and functional recovery. The results from the current study thus demonstrate a critical relationship between reperfused O 2 level and functional recovery in hypertrophic myocardium. The role of reperfused O 2, however, is time dependent. During early reperfusion, factor(s) other than O 2 appear to limit functional recovery. It is when the mechanical function of the heart approaches a new steady state that O 2 becomes a dominant factor. Meanwhile, the finding of a normal O 2 level in preischemic SHR hearts defies the notion of preexisting hypoxia as a primer of ischemic damage. left ventricular hypertrophy; myocardial ischemia; spontaneously hypertensive rat; nuclear magnetic resonance HYPERTROPHIED HEARTS show an increased susceptibility to ischemia (1,9,15, 31,39,53,55). The concentric left ventricular (LV) hypertrophy (LVH) is an adaptive response to chronic pressure overload, which involves multistep signaling pathways. After a period of compensated hypertrophic state, the hemodynamics of hypertrophic hearts gradually deteriorate and often culminate in heart failure. However, even before it develops overt hemodynamic failures, hypertrophic myocardium frequently displays signs of abnormalities, including an increased susceptibility to ischemia. Consequently, LVH is an independent risk factor for patients undergoing heart surgery. LVH is also characterized by diminished mechanical and energetic responses to the functionally ischemic conditions induced by high-workload challenges (6).Inflammatory and oxidative signals, including TNF-␣ or oxygen free radicals, might contribute to the increased susceptibility of hypertrophic myocardium to ischemia (31, 55). Yet many studies have also demonstrated an altered energy metabolism in LVH and have suggested a cellular hypoxia (15,41,61,64). Consistent with possible O 2 limitation, a depressed O 2 consumption in the hypertrophic myocardium, especially under low perfusion pressure, has...

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High-energy Phosphate Metabolism of the Myocardium in Normal Subjects and Patients with Various Cardiomyopathies. The study using ECG gated MR spectroscopy with a localization technique.

Cited by 34 publications

References 13 publications

Cyclical Changes in High-Energy Phosphates During the Cardiac Cycle by Pacing-Gated 31P Nuclear Magnetic Resonance

Cyclical Changes in High-Energy Phosphates During the Cardiac Cycle by Pacing-Gated 31P Nuclear Magnetic Resonance

Is the Failing Heart Energy Starved?

Oxygen reperfusion is limited in the postischemic hypertrophic myocardium

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