Time‐dependent changes in plasma xanthine oxidoreductase during hospitalization of acute heart failure

Abstract

Aims The aim of present study is to evaluate the clinical significance of the time-dependent changes in xanthine oxidoreductase (XOR) activity during hospitalization for acute heart failure (AHF). Methods and results A total of 229 AHF patients who visited to emergency room were prospectively enrolled, and 187 patients were analysed. Blood samples were collected within 15 min of admission (Day 1), after 48-72 h (Day 3), and between Days 7 and 21 (Day 14). The AHF patients were divided into two groups according to the XOR activity on Day 1: the high-XOR group (≥100 pmol/h/mL, n = 85) and the low-XOR group (<100 pmol/h/mL, n = 102). The high-XOR patients were assigned to two groups according to the rate of change in XOR from Day 1 to Day 14: the decreased group (≥50% decrease; n = 70) and the non-decreased group (<50% decrease; n = 15). The plasma XOR activity significantly decreased on Days 3 and 14 [23.6 (9.1 to 63.1) pmol/h/mL and 32.5 (10.2 to 87.8) pmol/h/mL, respectively] in comparison with Day 1 [78.5 (16.9 to 340.5) pmol/h/mL]. A Kaplan-Meier curve indicated that the prognosis, including heart failure (HF) events (all-cause death and readmission by HF) within 365 days, was significantly poorer in the low-XOR patients than in the high-XOR patients and was also significantly poorer in the non-decreased group than in the decreased group. Conclusions The plasma XOR activity was rapidly decreased by the appropriate treatment of AHF. Although high-XOR activity on admission was not associated with increased HF events in AHF, high-XOR activity that was not sufficiently reduced during appropriate treatment was associated with increased HF events.

Evaluation of Plasma Xanthine Oxidoreductase (XOR) Activity in Patients with Cardiopulmonary Arrest

“…10,11) Their technique enables the stable measurement of tiny amounts of human XOR activity in vivo. 9) Between 2019 and 2021, we have presented numerous lines of evidence regarding human XOR activity, such as in patients with AHF, recruited from out-patients clinics, and critically ill. [3][4][5][6][7] XOR produces ROS that might induce organ dysfunction. A previous study showed that a certain level of XOR was expressed on the vascular endothelium, wherein XO binds to glycosaminoglycan residues as a consequence of tissue damage such as ischemia and inflammation.…”

“…We also found that patients in whom high XOR activity was prolonged despite optimal therapy tended to have poor outcomes during AHF treatment. 7) If the AHF was not sufficiently compensated, the unstable hemodynamics would continue despite appropriate treatment/support, which would subsequently induce high XOR activity and adverse outcome. Moreover, we determined that high XOR activity led to high in-hospital mortality in the critically-ill patients.…”

“…We previously reported a number of novel findings on XOR activity. [3][4][5][6][7] Plasma XOR activity was extremely high in patients with severely decompensated AHF associated with high lactate levels, 3) and was rapidly decreased by appropriate AHF treatment approaches. 7) Furthermore, low plasma XOR activity was associated with malnutrition, renal dysfunction and aging in AHF.…”

“…[3][4][5][6][7] Plasma XOR activity was extremely high in patients with severely decompensated AHF associated with high lactate levels, 3) and was rapidly decreased by appropriate AHF treatment approaches. 7) Furthermore, low plasma XOR activity was associated with malnutrition, renal dysfunction and aging in AHF. 6) Although high XOR activity on admission was not associated with adverse outcomes in AHF, it was associated with a poor outcome if not sufficiently reduced by appropriate treatment.…”

“…6) Although high XOR activity on admission was not associated with adverse outcomes in AHF, it was associated with a poor outcome if not sufficiently reduced by appropriate treatment. 7) We also evaluated serum UA levels and plasma XOR activity in patients admitted to intensive care. 5,8) Serum UA level, which might be elevated by various critical stimuli on admission, was an independent predictor in patients who were emergently hospitalized in the intensivecare unit (ICU), which might be associated with high XOR activity.…”