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Published in: Heart and Vessels 10/2020

01-10-2020 | Xanthine Alkaloid | Original Article

Plasma xanthine oxidoreductase (XOR) activity in patients who require cardiovascular intensive care

Authors: Yusaku Shibata, Akihiro Shirakabe, Hirotake Okazaki, Masato Matsushita, Hiroki Goda, Shota Shigihara, Kazuhiro Asano, Kazutaka Kiuchi, Kenichi Tani, Takayo Murase, Takashi Nakamura, Nobuaki Kobayashi, Noritake Hata, Kuniya Asai, Wataru Shimizu

Published in: Heart and Vessels | Issue 10/2020

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Abstract

Hyperuricemia is known to be associated with adverse outcomes in cardiovascular intensive care patients, but its mechanisms are unknown. A total of 569 emergency department patients were prospectively analyzed and assigned to intensive care (ICU group, n = 431) or other departments (n = 138). Uric acid (UA) levels were significantly higher in the intensive care patients (6.3 [5.1–7.6] mg/dl vs. 5.8 [4.6–6.8] mg/dL). The plasma xanthine oxidoreductase (XOR) activity in the ICU group (68.3 [21.2–359.5] pmol/h/mL) was also significantly higher than that in other departments (37.2 [15.1–93.6] pmol/h/mL). Intensive care patients were divided into three groups according to plasma XOR quartiles (Q1, low-XOR, Q2/Q3, normal-XOR, and Q4, high-XOR group). A multivariate logistic regression model showed that lactate (per 1.0 mmol/L increase, OR 1.326; 95%, CI 1.166–1.508, p < 0.001) and the Acute Physiology and Chronic Health Evaluation II score (per 1.0 point increase, OR 1.095, 95% CI 1.034–1.160, p = 0.002) were independently associated with the high-XOR group. In-hospital mortality was significantly higher in the high-XOR group (n = 28, 26.2%) than in the normal- (n = 11, 5.1%) and low- (n = 9, 8.3%) XOR groups. The high-XOR group (vs. normal-XOR group) was independently associated with the in-hospital mortality (OR 2.934; 95% CI 1.170–7.358; p = 0.022). Serum UA levels and plasma XOR activity were high in patients admitted to intensive care. The enhanced XOR activity may be one of the mechanisms under which hyperuricemia was associated with adverse outcomes in patients requiring cardiovascular intensive care.
Literature
1.
go back to reference Okazaki H, Shirakabe A, Kobayashi N, Hata N, Shinada T, Matsushita M, Yamamoto Y, Shibuya J, Shiomura R, Nishigoori S, Asai K, Shimizu W (2016) The prognostic impact of uric acid in patients with severely decompensated acute heart failure. J Cardiol 68:384–391CrossRef Okazaki H, Shirakabe A, Kobayashi N, Hata N, Shinada T, Matsushita M, Yamamoto Y, Shibuya J, Shiomura R, Nishigoori S, Asai K, Shimizu W (2016) The prognostic impact of uric acid in patients with severely decompensated acute heart failure. J Cardiol 68:384–391CrossRef
2.
go back to reference Anker SD, Doehner W, Rauchhaus M, Sharma R, Francis D, Knosalla C, Davos CH, Cicoira M, Shamim W, Kemp M, Segal R, Osterziel KJ, Leyva F, Hetzer R, Ponikowski P, Coats AJ (2003) Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 107:1991–1997CrossRef Anker SD, Doehner W, Rauchhaus M, Sharma R, Francis D, Knosalla C, Davos CH, Cicoira M, Shamim W, Kemp M, Segal R, Osterziel KJ, Leyva F, Hetzer R, Ponikowski P, Coats AJ (2003) Uric acid and survival in chronic heart failure: validation and application in metabolic, functional, and hemodynamic staging. Circulation 107:1991–1997CrossRef
3.
go back to reference Kobayashi N, Hata N, Tsurumi M, Shibata Y, Okazaki H, Shirakabe A, Takano M, Seino Y, Shimizu W (2018) Relation of coronary culprit lesion morphology determined by optical coherence tomography and cardiac outcomes to serum uric acid levels in patients with acute coronary syndrome. Am J Cardiol 122:17–25CrossRef Kobayashi N, Hata N, Tsurumi M, Shibata Y, Okazaki H, Shirakabe A, Takano M, Seino Y, Shimizu W (2018) Relation of coronary culprit lesion morphology determined by optical coherence tomography and cardiac outcomes to serum uric acid levels in patients with acute coronary syndrome. Am J Cardiol 122:17–25CrossRef
4.
go back to reference Pagidipati NJ, Hess CN, Clare RM, Akerblom A, Tricoci P, Wojdyla D, Keenan RT, James S, Held C, Mahaffey KW, Klein AB, Wallentin L, Roe MT (2017) An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome. Am Heart J 187:53–61CrossRef Pagidipati NJ, Hess CN, Clare RM, Akerblom A, Tricoci P, Wojdyla D, Keenan RT, James S, Held C, Mahaffey KW, Klein AB, Wallentin L, Roe MT (2017) An examination of the relationship between serum uric acid level, a clinical history of gout, and cardiovascular outcomes among patients with acute coronary syndrome. Am Heart J 187:53–61CrossRef
5.
go back to reference Pehlivanlar-Kucuk M, Kucuk AO, Ozturk CE, Er MC, Ulger F (2018) The association between serum uric acid level and prognosis in critically ill patients, uric acid as a prognosis predictor. Clin Lab 64:1491–1500CrossRef Pehlivanlar-Kucuk M, Kucuk AO, Ozturk CE, Er MC, Ulger F (2018) The association between serum uric acid level and prognosis in critically ill patients, uric acid as a prognosis predictor. Clin Lab 64:1491–1500CrossRef
6.
go back to reference Shibata Y, Shirakabe A, Okazaki H, Matsushita M, Sawatani T, Uchiyama S, Tani K, Kobayashi N, Otsuka T, Hata N, Asai K, Shimizu W (2019) The prognostic impact of the uric acid level in patients who require cardiovascular intensive care - is serum uric acid a surrogate biomarker for critical patients in the non-surgical intensive care unit? EHJ Acute Cardovasc Care. https://doi.org/10.1177/2048872618822473CrossRef Shibata Y, Shirakabe A, Okazaki H, Matsushita M, Sawatani T, Uchiyama S, Tani K, Kobayashi N, Otsuka T, Hata N, Asai K, Shimizu W (2019) The prognostic impact of the uric acid level in patients who require cardiovascular intensive care - is serum uric acid a surrogate biomarker for critical patients in the non-surgical intensive care unit? EHJ Acute Cardovasc Care. https://​doi.​org/​10.​1177/​2048872618822473​CrossRef
7.
go back to reference Agarwal A, Banerjee A, Banerjee UC (2011) Xanthine oxidoreductase: a journey from purine metabolism to cardiovascular excitation-contraction coupling. Crit Rev Biotechnol 31:264–280CrossRef Agarwal A, Banerjee A, Banerjee UC (2011) Xanthine oxidoreductase: a journey from purine metabolism to cardiovascular excitation-contraction coupling. Crit Rev Biotechnol 31:264–280CrossRef
8.
go back to reference Robert AM, Robert L (2014) Xanthine oxido-reductase, free radicals and cardiovascular disease. A critical review. Pathol Oncol Res 20:1–10CrossRef Robert AM, Robert L (2014) Xanthine oxido-reductase, free radicals and cardiovascular disease. A critical review. Pathol Oncol Res 20:1–10CrossRef
9.
go back to reference Otaki Y, Watanabe T, Kinoshita D, Yokoyama M, Takahashi T, Toshima T, Sugai T, Murase T, Nakamura T, Nishiyama S, Takahashi H, Arimoto T, Shishido T, Miyamoto T, Kubota I (2017) Association of plasma xanthine oxidoreductase activity with severity and clinical outcome in patients with chronic heart failure. Int J Cardiol 228:151–157CrossRef Otaki Y, Watanabe T, Kinoshita D, Yokoyama M, Takahashi T, Toshima T, Sugai T, Murase T, Nakamura T, Nishiyama S, Takahashi H, Arimoto T, Shishido T, Miyamoto T, Kubota I (2017) Association of plasma xanthine oxidoreductase activity with severity and clinical outcome in patients with chronic heart failure. Int J Cardiol 228:151–157CrossRef
10.
go back to reference Okazaki H, Shirakabe A, Matsushita M, Shibata Y, Sawatani T, Uchiyama S, Tani K, Murase T, Nakamura T, Takayasu T, Asano M, Kobayashi N, Hata N, Asai K, Shimizu W (2019) Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care. ESC Heart Failure 6:336–343CrossRef Okazaki H, Shirakabe A, Matsushita M, Shibata Y, Sawatani T, Uchiyama S, Tani K, Murase T, Nakamura T, Takayasu T, Asano M, Kobayashi N, Hata N, Asai K, Shimizu W (2019) Plasma xanthine oxidoreductase activity in patients with decompensated acute heart failure requiring intensive care. ESC Heart Failure 6:336–343CrossRef
11.
go back to reference Nakatani A, Nakatani S, Ishimura E, Murase T, Nakamura T, Sakura M, Tateishi Y, Tsuda A, Kurajoh M, Mori K, Emoto M, Inaba M (2017) Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients. Sci Rep 7:15416CrossRef Nakatani A, Nakatani S, Ishimura E, Murase T, Nakamura T, Sakura M, Tateishi Y, Tsuda A, Kurajoh M, Mori K, Emoto M, Inaba M (2017) Xanthine oxidoreductase activity is associated with serum uric acid and glycemic control in hemodialysis patients. Sci Rep 7:15416CrossRef
12.
go back to reference Washio KW, Kusunoki Y, Murase T, Nakamura T, Osugi K, Ohigashi M, Sukenaga T, Ochi F, Matsuo T, Katsuno T, Moriwaki Y, Yamamoto T, Namba M, Koyama H (2017) Xanthine oxidoreductase activity is correlated with insulin resistance and subclinical inflammation in young humans. Metabolism 70:51–56CrossRef Washio KW, Kusunoki Y, Murase T, Nakamura T, Osugi K, Ohigashi M, Sukenaga T, Ochi F, Matsuo T, Katsuno T, Moriwaki Y, Yamamoto T, Namba M, Koyama H (2017) Xanthine oxidoreductase activity is correlated with insulin resistance and subclinical inflammation in young humans. Metabolism 70:51–56CrossRef
13.
go back to reference Furuhashi M, Matsumoto M, Tanaka M, Moniwa N, Murase T, Nakamura T, Ohnishi H, Saitoh S, Shimamoto K, Miura T (2018) Plasma xanthine oxidoreductase activity as a novel biomarker of metabolic disorders in a general population. Circ J 82:1892–1899CrossRef Furuhashi M, Matsumoto M, Tanaka M, Moniwa N, Murase T, Nakamura T, Ohnishi H, Saitoh S, Shimamoto K, Miura T (2018) Plasma xanthine oxidoreductase activity as a novel biomarker of metabolic disorders in a general population. Circ J 82:1892–1899CrossRef
14.
go back to reference Fujimura Y, Yamauchi Y, Murase T, Nakamura T, Fujita SI, Fujisaka T, Ito T, Sohmiya K, Hoshiga M, Ishizaka N (2017) Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients. PLoS ONE 12:e0182699CrossRef Fujimura Y, Yamauchi Y, Murase T, Nakamura T, Fujita SI, Fujisaka T, Ito T, Sohmiya K, Hoshiga M, Ishizaka N (2017) Relationship between plasma xanthine oxidoreductase activity and left ventricular ejection fraction and hypertrophy among cardiac patients. PLoS ONE 12:e0182699CrossRef
15.
go back to reference Murase T, Nampei M, Oka M, Miyachi A, Nakamura T (2016) A highly sensitive assay of human plasma xanthine oxidoreductase activity using stable isotope-labeled xanthine and LC/TQMS. J Chromatogr B Analyt Technol Biomed Life Sci 1039:51–58CrossRef Murase T, Nampei M, Oka M, Miyachi A, Nakamura T (2016) A highly sensitive assay of human plasma xanthine oxidoreductase activity using stable isotope-labeled xanthine and LC/TQMS. J Chromatogr B Analyt Technol Biomed Life Sci 1039:51–58CrossRef
16.
go back to reference Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Critical Care Med 13:818–829CrossRef Knaus WA, Draper EA, Wagner DP, Zimmerman JE (1985) APACHE II: a severity of disease classification system. Critical Care Med 13:818–829CrossRef
17.
go back to reference Murase T, Nampei M, Oka M, Ashizawa N, Matsumoto K, Miyachi A, Nakamura T (2016) Xanthine oxidoreductase activity assay in tissues using stable isotope-labeled substrate and liquid chromatography high-resolution mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1008:189–197CrossRef Murase T, Nampei M, Oka M, Ashizawa N, Matsumoto K, Miyachi A, Nakamura T (2016) Xanthine oxidoreductase activity assay in tissues using stable isotope-labeled substrate and liquid chromatography high-resolution mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1008:189–197CrossRef
18.
go back to reference Murase T, Oka M, Nampei M, Miyachi A, Nakamura T (2016) A highly sensitive assay for xanthine oxidoreductase activity using a combination of [(13) C2, (15) N2 ]xanthine and liquid chromatography/triple quadrupole mass spectrometry. J Labelled Comp Radiopharm 59:214–220CrossRef Murase T, Oka M, Nampei M, Miyachi A, Nakamura T (2016) A highly sensitive assay for xanthine oxidoreductase activity using a combination of [(13) C2, (15) N2 ]xanthine and liquid chromatography/triple quadrupole mass spectrometry. J Labelled Comp Radiopharm 59:214–220CrossRef
19.
go back to reference Watanabe K, Shishido T, Otaki Y, Watanabe T, Sugai T, Toshima T, Takahashi T, Yokoyama M, Kinoshita D, Murase T, Nakamura T, Wanezaki M, Tamura H, Nishiyama S, Takahashi H, Arimoto T, Yamauchi S, Yamanaka T, Miyamoto T, Kubota I, Watanabe M (2018) Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm. Heart Vessels 34:1–8CrossRef Watanabe K, Shishido T, Otaki Y, Watanabe T, Sugai T, Toshima T, Takahashi T, Yokoyama M, Kinoshita D, Murase T, Nakamura T, Wanezaki M, Tamura H, Nishiyama S, Takahashi H, Arimoto T, Yamauchi S, Yamanaka T, Miyamoto T, Kubota I, Watanabe M (2018) Increased plasma xanthine oxidoreductase activity deteriorates coronary artery spasm. Heart Vessels 34:1–8CrossRef
20.
go back to reference Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, Reepschlager N, Hornig B, Drexler H, Harrison DG (2003) Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 107:1383–1389CrossRef Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, Reepschlager N, Hornig B, Drexler H, Harrison DG (2003) Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 107:1383–1389CrossRef
21.
go back to reference Ali OS, Abdelgawad HM, Mohammed MS, El-Awady RR (2014) Ischemic heart diseases in Egypt: role of xanthine oxidase system and ischemia-modified albumin. Heart Vessels 29:629–637CrossRef Ali OS, Abdelgawad HM, Mohammed MS, El-Awady RR (2014) Ischemic heart diseases in Egypt: role of xanthine oxidase system and ischemia-modified albumin. Heart Vessels 29:629–637CrossRef
22.
go back to reference Kurajoh M, Fukumoto S, Emoto M, Murase T, Nakamura T, Ishihara T, Go H, Yamamoto K, Nakatani S, Tsuda A, Yamada S, Morioka T, Mori K, Imanishi Y, Inaba M (2019) Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry. Clin Chem Lab Med. https://doi.org/10.1515/cclm-2019-0199CrossRef Kurajoh M, Fukumoto S, Emoto M, Murase T, Nakamura T, Ishihara T, Go H, Yamamoto K, Nakatani S, Tsuda A, Yamada S, Morioka T, Mori K, Imanishi Y, Inaba M (2019) Independent association of plasma xanthine oxidoreductase activity with serum uric acid level based on stable isotope-labeled xanthine and liquid chromatography/triple quadrupole mass spectrometry: MedCity21 health examination registry. Clin Chem Lab Med. https://​doi.​org/​10.​1515/​cclm-2019-0199CrossRef
23.
go back to reference Pacher P, Nivorozhkin A, Szabo C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114CrossRef Pacher P, Nivorozhkin A, Szabo C (2006) Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol Rev 58:87–114CrossRef
24.
go back to reference Narsale AA, Enos RT, Puppa MJ, Chatterjee S, Murphy EA, Fayad R, Pena MO, Durstine JL, Carson JA (2015) Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression. PLoS ONE 10:e0119888CrossRef Narsale AA, Enos RT, Puppa MJ, Chatterjee S, Murphy EA, Fayad R, Pena MO, Durstine JL, Carson JA (2015) Liver inflammation and metabolic signaling in ApcMin/+ mice: the role of cachexia progression. PLoS ONE 10:e0119888CrossRef
25.
go back to reference Kelley EE (2015) Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase. Arch Toxicol 89:1193–1207CrossRef Kelley EE (2015) Dispelling dogma and misconceptions regarding the most pharmacologically targetable source of reactive species in inflammatory disease, xanthine oxidoreductase. Arch Toxicol 89:1193–1207CrossRef
Metadata
Title
Plasma xanthine oxidoreductase (XOR) activity in patients who require cardiovascular intensive care
Authors
Yusaku Shibata
Akihiro Shirakabe
Hirotake Okazaki
Masato Matsushita
Hiroki Goda
Shota Shigihara
Kazuhiro Asano
Kazutaka Kiuchi
Kenichi Tani
Takayo Murase
Takashi Nakamura
Nobuaki Kobayashi
Noritake Hata
Kuniya Asai
Wataru Shimizu
Publication date
01-10-2020
Publisher
Springer Japan
Published in
Heart and Vessels / Issue 10/2020
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-020-01608-x

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