Oxidative stress and abnormal cholesterol metabolism in patients with post-cardiac arrest syndrome

Abstract

Patients with post-cardiac arrest syndrome (PCAS) suffer from whole body ischemia/reperfusion injury similar to that experienced by newborn babies. Increased oxidative stress was confirmed in PCAS patients (n = 40) at the time of hospitalization by a significant increase in the percentage of the oxidized form of coenzyme Q10 in total coenzyme Q10 compared to age-matched healthy controls (n = 55). Tissue oxidative damage in patients was suggested by the significant increase in plasma levels of free fatty acids (FFA) and the significant decrease in polyunsaturated fatty acid contents in total FFA. A greater decrease in free cholesterol (FC) compared to cholesterol esters (CE) was observed. Therefore, the FC/CE ratio significantly increased, suggesting deficiency of lecithin-cholesterol acyltransferase secreted from the liver. Time course changes of the above parameters were compared among 6 groups of patients divided according to outcome severity. Rapid declines of FC and CE were observed in patients who died within a day, while levels remained unchanged in patients discharged in a week. These data suggest that liver function is one of the key factors determining the survival of patients. Interestingly, therapeutic hypothermia treatment enhanced the increment of plasma ratio of coenzyme Q10 to total cholesterol at the end of rewarming.

Keywords: cholesterol metabolism; coenzyme Q10; plasma free fatty acids; prosaposin; therapeutic hypothermia.

Fig. 1

Time course of changes in the percentage of the oxidized form of coenzyme Q10 in TQ10 (%CoQ10) after hospitalization. Patients were divided into six groups according to outcome. Average %CoQ10 in age-matched healthy controls was 3.9 ± 1.3 (± SD, n = 55); this range is shaded in green.

Fig. 2

Time course of changes in plasma total coenzyme Q10 (TQ10) after hospitalization. Patients were divided into six groups according to outcome. The average TQ10 level in age-matched healthy controls was 710 ± 206 µM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test.

Fig. 3

Time course of changes in plasma vitamin E (VE) after hospitalization. Patients were divided into six groups according to outcome. The average VE level in age-matched healthy controls was 28.5 ± 7.3 µM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test. P values are indicated when one-way repeated ANOVA analysis was significant.

Fig. 4

Time course of changes in plasma total cholesterol (TC) after hospitalization. Patients were divided into six groups according to outcome. The average TC level in age-matched healthy controls was 4.72 ± 0.94 mM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired a Student’s t test. P values are indicated when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 5

Time course of changes in plasma cholesterol esters (CE) after hospitalization. Patients were divided into six groups according to outcome. The average CE level in age-matched healthy controls was 3.36 ± 0.72 mM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test. P values are indicated when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 6

Time course of changes in plasma free cholesterol (FC) after hospitalization. Patients were divided into six groups according to outcome. The average FC level in age-matched healthy controls was 1.37 ± 0.25 mM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test. P values are indicated when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 7

Time course of changes in plasma ratio of free cholesterol to cholesterol esters (FC/CE) after hospitalization. Patients were divided into six groups according to outcome. The average FC/CE ratio in age-matched healthy controls was 0.41 ± 0.05 (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test. P values are shown when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 8

Time course of changes in plasma ascorbic acid (VC) after hospitalization. Patients were divided into six groups according to outcome. The average VC level in age-matched healthy controls was 31.1 ± 21.0 µM (± SD, n = 55); this range is shaded in green. P values are shown when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 9

Time course of changes in plasma uric acid (UA) after hospitalization. Patients were divided into six groups according to outcome. The average UA level in age-matched healthy controls was 317 ± 86 µM (± SD, n = 55); this range is shaded in green. ^#p<0.05, significant differences compared to values at 0 h as determined by a paired Student’s t test. P values are shown when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 0 h as determined by the Tukey–Kramer multiple comparisons test.

Fig. 10

Time course of changes in plasma free fatty acids (FFA), the percentage of polyunsaturated fatty acids in total FFA (%PUFA), the percentage of palmitoleic acid in total FFA (%16:1), and the percentage of oleic acid in total FFA (%18:1) after hospitalization. Patients were divided into three groups according to outcome. The average FFA level, %PFA, %16:1, and %18:1 in age-matched healthy controls were 457 ± 288 µM, 23.6 ± 4.6, 3.9 ± 1.4, and 34.4 ± 5.1, respectively (± SD, n = 55); these ranges are shaded in green. ^#p<0.05 and ^###p<0.001, significant differences compared to values at 0 h as determined by a paired Student’s t test.

Fig. 11

Time course of changes in ratio of plasma total coenzyme Q10 to total cholesterol (TQ10/TC) and plasma prosaposin (Psap) after hospitalization. Patients were divided into groups with (n = 22) and without (n = 6) therapeutic hypothermia (TH) treatment. The average Psap level and TQ10/TC ratio in age-matched healthy controls were 27.2 ± 5.8 nM (± SD, n = 80) and 180 ± 86 nM/mM (± SD, n = 55), respectively; these ranges are shaded in green. P values are shown when one-way repeated ANOVA analysis was significant. *p<0.05, significant differences compared to values at 48 h as determined by the Tukey–Kramer multiple comparisons test.