Evaluation of Functional Recovery of Regenerating Rat Liver after Partial Hepatectomy Using31P-NMR Spectroscopy

Nishida, Yasunori; Tanaka, Kunio; Munakata, Takashi; Kasai, S.

doi:10.1006/jsre.1996.0134

Cited by 3 publications

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“…38,39 After hepatic resection, the remnant liver is known to undergo energetic changes, as documented by in vitro experiments [35][36][37][40][41][42] and invasive MRS studies, in which laparotomies were performed and a phosphorus surface coil was placed directly on the liver. 17,18,20,42 To date, the present study along with a report by Kooby et al 19 are the only published reports to have quantitatively documented hepatic energy levels following PHx noninvasively with 31 P-MRS. Localized spectral data 24 hours following PHx depicted a decrease in hepatic ATP/Pi among hepatectomized rats, but, interestingly, it arose not because of lowered ATP levels but as a result of increased hepatic Pi.…”

Section: Discussionmentioning

confidence: 49%

“…Initial animal studies have been performed in which in vivo 31 P-MRS has been used to document metabolic changes in the liver following PHx. [17][18][19][20] All studies consistently report changes in the energetic status of the liver, as reflected by the ratio of ATP/Pi, throughout the postoperative period. These studies, however, failed to elucidate the significance of ATP/Pi in relation to hepatic regeneration or dysfunction, insofar as direct correlations were not performed with either parameter.…”

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confidence: 99%

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Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

et al. 2002

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The aim of the present study was to determine whether alterations in hepatic energy expenditure following partial hepatectomy (PHx), as documented by in vivo hepatic 31 P-MRS, correlate with standard parameters of hepatic regeneration and/or liver function. In addition, we sought to determine whether changes in hepatic energy levels are proportional to the extent of hepatic resection. Adult male Sprague-Dawley rats (4-7 per group) underwent a 40%, 70%, or 90% PHx or sham surgeries. Magnetic resonance spectroscopy (MRS) examinations were performed on each animal 24 or 48 hours thereafter. After MRS examinations, [ 3 H]thymidine incorporation into hepatic DNA, proliferating cell nuclear antigen (PCNA) protein expression, and serum bilirubin determinations were performed on each rat. Twenty-four hours following surgery, rats that had undergone 70% PHx had unchanged adenosine triphosphate (ATP) levels but significantly lower ATP/inorganic phosphate (Pi) ratios (P < .05), whereas, at 48 hours post-PHx, both ATP and ATP/Pi levels were lower than in sham-and nonoperated controls (P < .05). Hepatic regeneration and liver dysfunction mirrored these changes; correlations existed between ATP/Pi ratios and [ 3 H]thymidine incorporation (r ‫؍‬ ؊0.61, P < .005), PCNA protein expression (r ‫؍‬ ؊0.62, P < .005), and serum bilirubin (r ‫؍‬ ؊0.49, P < .05). For rats that had undergone graded resections, depleted energy levels 48 hours post-PHx were proportional to the extent of resection, degree of enhanced regenerative activity, and liver dysfunction. In conclusion, 31 P-MRS-generated ATP/Pi index is a noninvasive, robust determination that correlates with standard parameters of hepatic regeneration and function. (HEPATOLOGY 2002;36:345-353.)

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Section: Discussionmentioning

confidence: 49%

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confidence: 99%

Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

et al. 2002

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“…Increased activity of this enzyme may explain why PC has been shown to decrease transiently (normalized within 48 hr) after PH in rats (22). The reduction in NTP observed in the patients is likely due to the increased demand for high‐energy phosphates to provide energy for DNA synthesis and mitosis (7), as well as protein synthesis (29). Additionally, the remaining liver rapidly assumes all of the normal functions that were performed by the total liver prior to surgery (24).…”

Section: Discussionmentioning

confidence: 99%

Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: Assessment using proton‐decoupled ³¹P‐ magnetic resonance spectroscopic imaging

Zakian

Koutcher

Malhotra

et al. 2005

Magnetic Resonance in Med

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In the present study we applied proton-decoupled 31 P magnetic resonance spectroscopic imaging (MRSI) to noninvasively assess liver metabolism in patients who had undergone a partial hepatectomy (PH). Proton-decoupled 31 P chemical shift imaging was performed in 47 patients 2-28 days following major hepatectomy, and the results were compared with those from eight control subjects. All studies were performed on a 1.5T MR imager (General Electric, Milwaukee, WI) equipped with a stand-alone proton decoupler. A 31 P-1 H resonator pair was used for data acquisition, and 31 P data were obtained in 34 min. Liver regeneration was characterized by increases in phosphoethanolamine (PE), and decreases in nucleoside triphosphates (NTP), glycerophosphoethanolamine (GPE), and glycerophosphocholine (GPC). These alterations were most marked 48 -72 hr after hepatectomy and returned to baseline within 3 weeks. The level of PE measured by MRSI was also found to depend on the percentage of liver that was removed, while changes in levels of cellular high energy phosphates were independent of the size of liver resection. Implementation of proton-decoupling was critical for assessing individual phosphomonoester and phosphodiester components. This study demonstrates that 31 P MRSI can be used to assess metabolic changes in humans during liver regeneration, and may be useful for assessing derangement of the regenerative process or guiding adjuvant chemotherapies. The regenerative capacity of the liver is the underlying basis of the approximately 50000 liver resections performed yearly in this country to treat benign and malignant diseases (1). Resections of up to 90% of functional liver parenchyma are now performed at many major centers around the world, and mortality rates are routinely less than 3% (2-4). Almost all knowledge of the cellular physiology of the hepatic regenerative process has been derived from animal studies, particularly in rodents (5). It is known that Ͼ85% of the rat hepatocytes proceed into S-phase within 48 hr after partial hepatectomy (PH), and that cellular stores of high-energy phosphates decrease and then normalize within 5-7 days (6 -8). Until recently, studies of liver regeneration in humans have been restricted to volumetric assessments of regeneration by cross-sectional imaging, or to measurements of hepatocyte-synthetic capacity (9,10). Both of these parameters usually recover late in the course of liver regeneration. There is also great variability in the data regarding the time course of liver volume recovery, with estimates ranging from 3 weeks to several months (9,11).In the present study we utilized proton-decoupled 31 P magnetic resonance spectroscopic imaging (MRSI) to noninvasively assess liver metabolism in patients following major hepatectomy. This technique permits the measurement of cellular high-energy phosphates, individual cell membrane phospholipid metabolites (phosphoethanolamine (PE), phosphocholine (PC), glycerophosphoethanolamine (GPE), and glycerophosphocholine (GPC)), and intracellul...

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“…Nishida et al [19] reported that ATP levels in remnant liver at 60 min after portal vein declamping return to normal 4 weeks after partial hepatectomy. So there is a possibility that a latent deficiency of the energy state and metabolic changes in the regenerating liver decrease the UDP-GA synthesis.…”

Section: Figmentioning

confidence: 97%

Experimental Study on the Bilirubin Metabolism after Major Hepatectomy: Alterations in the Proportions of Bile Bilirubin Subfractions

Igarashi

Ishiyama

Urayama

et al. 1999

Journal of Surgical Research

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Evaluation of Functional Recovery of Regenerating Rat Liver after Partial Hepatectomy Using31P-NMR Spectroscopy

Cited by 3 publications

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Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: Assessment using proton‐decoupled ³¹P‐ magnetic resonance spectroscopic imaging

Experimental Study on the Bilirubin Metabolism after Major Hepatectomy: Alterations in the Proportions of Bile Bilirubin Subfractions

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Evaluation of Functional Recovery of Regenerating Rat Liver after Partial Hepatectomy Using31P-NMR Spectroscopy

Cited by 3 publications

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Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

Regenerative activity and liver function following partial hepatectomy in the rat using 31P-MR spectroscopy

Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: Assessment using proton‐decoupled 31P‐ magnetic resonance spectroscopic imaging

Experimental Study on the Bilirubin Metabolism after Major Hepatectomy: Alterations in the Proportions of Bile Bilirubin Subfractions

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Liver regeneration in humans is characterized by significant changes in cellular phosphorus metabolism: Assessment using proton‐decoupled ³¹P‐ magnetic resonance spectroscopic imaging