Figure 1.
BIS monitoring in the rabbit.
Figure 2.
General view of the experimental area.
Table 1.
The amount of total fluids and drugs given intravenously, serum CoQ10 levels and the time to death, and survival ratio at the 24th hour after the start of propofol infusion or sevofurane inhalation
| Propofol | Propofol + CoQ10 | Sevoflurane | Sevoflurane + CoQ10 | P value | |
|---|---|---|---|---|---|
| Total fluid given (mL) | 341 (225–875) | 186 (100–300) | 284 (200–390) | 170 (155–200) | 0.057 |
| Total urine output (mL) | 160 (85–650) | 40 (20–100) | 150 (50–170) | 85 (50–100) | 0.073 |
| Total bicarbonate | 5 (0–50) | 0 (0–10) | 0 (0–10) | 0 (0–0) | 0.424 |
| Total propofol (mg) | 1400 (980–2200) | 1050 (760–2000) | 0 (0–0) | 0 (0–0) | NA |
| Serum CoQ10 level (μg/mL) – basal | 0.14 (0.09–0.39) | 0.1 (0.06–0.23) | 0.26 (0.16–0.56) | 0.13 (0.05–0.21) | 0.131 |
| Serum CoQ10 level (μg/mL) – 12th hour | 0.41 (0.38–0.45) | 0.23 (0.12–0.36) | 0.28 (0.08–0.58) | 0.16 (0.09–0.25) | 0.356 |
| Serum CoQ10 level (μg/mL) – 24th hour | N = 0 | 0.38 (N = 1) | 0.24 (N = 1) | 0.23 (0.11–0.34) | NA |
| Time to death (h) | 12 (6–20) | 18 (16–24) | 20 (17–24) | 23 (20–24) | 0.066 |
| Survival ratio (%) – 24th hour | 0 (0) | 1 (25) | 1 (25) | 2 (50) | 0.446 |
[i] Data are given as median (minimum–maximum) or percentage.
[ii] CoQ10, coenzyme Q10; N, number of animals alive; NA, not available.
Table 2.
The laboratory results of the four experimental groups
| Propofol | Propofol + CoQ10 | Sevoflurane | Sevoflurane + CoQ10 | P value | |
|---|---|---|---|---|---|
| PH – basal | 7.37 (7.17–7.64) | 7.4 (7.19–7.55) | 7.43 (7.17–7.64) | 7.35 (7.25–7.5) | 0.980 |
| pH – 12th hour | 7.40 (7.15–7.47) | 7.15 (7.15–7.15) | 7.37 (7.28–7.47) | 7.4 (7.28–7.46) | 0.804 |
| PaCO2 – basal (mmHg) | 44.5 (14–63) | 42 (41–48) | 53.5 (14–61) | 30 (22–47) | 0.481 |
| PaCO2 – 12th hour (mmHg) | 26 (20–38) | 34 (34–34) | 25 (24–26) | 27 (20–38) | 0.595 |
| PaO2 – basal (mmHg) | 249 (149–371) | 258 (214–266) | 256 (149–316) | 217 (208–251) | 0.752 |
| PaO2 – 12th hour (mmHg) | 240 (56–391) | 116 (116–116) | 301.5 (228–375) | 273 (185–380) | 0.508 |
| Ca+2 – basal (mmol/L) | 1.3 (1–1.75) | 1.5 (1.52–1.75) | 1.42 (1–1.69) | 1.27 (1.07–1.35) | 0.237 |
| Ca+2 – 12th hour (mmol/L) | 1.45 (0.4–1.61) | 0.4 (0.4–0.4) | 1.34 (1.24–1.45) | 1.5 (0.57–1.51) | 0.258 |
| Glucose – basal (mg/dL) | 299 (135–467) | 307 (268–308) | 294 (226–463) | 320 (135–467) | 0.938 |
| Glucose – 12th hour (mg/dL) | 111 (47–234) | 47 (47–47) | 93.5 (76–111) | 144 (121–234) | 0.162 |
| Lactate – basal (mmol/L) | 2.85 (1–10.5) | 4 (1.2–10.5) | 1.4 (1–3.2) | 4.3 (3.9–5.2) | 0.190 |
| Lactate – 12th hour (mmol/L) | 5 (3.1–8.8) | 4.3 (4.3–4.3) | 4.05 (3.1–5) | 5.3 (3.2–8.8) | 0.855 |
| HCO3 – basal (mmol/L) | 26 (9.6–36.4) | 26 (18.3–36) | 28 (15.1–34.7) | 23.4 (9.6–25.9) | 0.548 |
| HCO3 – 12th hour (mmol/L) | 16.7 (11.8–19.5) | 11.8 (11.8–11.8) | 16 (14.8–17.2) | 16.7 (14.2–17.9) | 0.277 |
| BE – basal (mmol/L) | 0.35 (−17.6 to 13.5) | 1.2 (−9.9 to 13.5) | 3.6 (−6.2 to 11.1) | 0.2 (−17.6 to 0.3) | 0.586 |
| BE – 12th hour (mmol/L) | −7.2 (−17.1 to 14.2) | −17.1 (−17.1 to 17.1) | −10.1 (−13 to 7.2) | 8.8 (−8.1 to 14.2) | 0.294 |
| Hematocrit – basal (%) | 34 (30–38) | 41 (35–46) | 37 (35–48) | 37 (35–40) | 0.282 |
| Hematocrit – 12th hour (%) | 34 (34–34) | 41 (38–45) | 29 (22–43) | 35 (33–42) | 0.141 |
| ALT – basal (U/L) | 32 (26–141) | 59 (44–68) | 63 (33–163) | 95 (62–110) | 0.484 |
| ALT – 12th hour (U/L) | 84 (29–254) | 86 (63–214) | 252 (37–440) | 112 (93–487) | 0.606 |
| AST – basal (U/L) | 86 (10–518) | 38 (28–41) | 46 (25–108) | 53 (30–74) | 0.606 |
| AST – 12th hour (U/L) | 202 (100–1166) | 106 (90–820) | 509 (107–1421) | 98 (89–627) | 0.409 |
| GGT – basal (U/L) | 9 (7–21) | 12 (8–18) | 8 (6–21) | 12 (9–15) | 0.628 |
| GGT – 12th hour (U/L) | 9 (4–16) | 10 (7–102) | 9 (7–16) | 16 (9–17) | 0.676 |
| Creatinine – basal (mg/dL) | 1.08 (0.9–1.20) | 1.12 (1.1–1.16) | 1.01 (0.8–1.15) | 0.9 (0.9–1.02) | 0.204 |
| Creatinine – 12th hour (mg/dL) | 1.6 (0.8–3) | 2.14 (1.35–4.33) | 1.2 (0.9–3.2) | 1.4 (1.2–2.14) | 0.631 |
| LDH – basal (U/L) | 746 (688–900) | 932 (444–1540) | 689 (600–720) | 629 (362–1410) | 0.508 |
| LDH – 12th hour (U/L) | 1356 (1287–2200) | 1654 (1500–1944) | 1891 (1748–2595) | 845 (814–877) | 0.078 |
| CK – basal hour (U/L) | 1847 (902–2137) | 2922 (2545–3300) | 1683 (1436–2089) | 1724 (1305–2203) | 0.191 |
| CK – 12th hour (U/L) | 3838 (2961–5876) | 3118 (2900–5402) | 4236 (3594–9921) | 11415 (6000–12769) | 0.117 |
| Amylase – basal (U/L) | 289 (281–350) | 285 (246–356) | 286 (218–333) | 291 (231–310) | 0.820 |
| Amylase – 12th hour (U/L) | 485 (440–625) | 371 (323–605) | 341 (291–510) | 449 (364–1084) | 0.289 |
| Troponin T – basal (ng/mL) | 0.03 (0.01–0.8) | 0.005 (0–0.001) | 0.05 (0.01–0.18) | 0.01 (0–0.01) | 0.535 |
| Troponin T – 12th hour (ng/mL) | 0.94 (0.2–3.5) | 0.005 (0–0.026)*, # | 0.15 (0.13–0.2)* | 0.01 (0–0.01)*, # | 0.007 |
| Cholesterol – basal (mg/dL) | 49 (32–55) | 30 (27–57) | 47 (27–92) | 32 (29–82) | 0.795 |
| Cholesterol – 12th hour (mg/dL) | 119 (64–134) | 119 (43–124) | 49 (24–81) | 48 (29–68) | 0.138 |
| Triglicerides – basal (mg/dL) | 156 (62–201) | 168 (67–270) | 60 (43–84) | 92 (98–152) | 0.139 |
| Triglicerides – 12th hour (mg/dL) | 993 (663–5460) | 1013 (213–1549)# | 106 (62–270)* | 325 (126–525) | 0.038 |
Data are given as median (minimum–maximum).
* P < 0.05 when compared with the propofol group. (P = 0.07: the propofol infusion group had the highest troponin T levels when compared with the other three groups.)
# P < 0.05 when compared with the sevoflurane group. (P = 0.038: Propofol infusion caused higher trigliceride levels than sevoflurane inhalation; anesthesia and CoQ10 did not have any protective effect on increased trigliceride levels.)
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BE, base excess; Ca, calcium; CK, creatinine kinase; CoQ10, coenzyme Q10; GGT, gamma-glutamyl transpeptidase; HCO3, bicarbonate; LDH, lactate dehydrogenase; PaCO2, partial arterial carbon dioxide pressure; PaO2, partial arterial oxygen pressure.
Table 3.
The histopathologic organ injury scores
| Propofol | Propofol + CoQ10 | Sevoflurane | Sevoflurane + CoQ10 | P value | |
|---|---|---|---|---|---|
| Lung | |||||
| Pulmonary edema | 2.5 (2–3) | 2.5 (1–3) | 2.5 (2–3) | 2.5 (2–3) | 0.983 |
| Parenchymal congestion | 3 (2–3) | 2.5 (2–3) | 2.5 (2–3) | 2.5 (2–3) | 0.870 |
| Alveolar hemorrhage | 1 (1–2) | 1 (1–3) | 1 (1–2) | 1 (1–1) | 0.794 |
| Inflammation | 2 (2–2) | 2 (1–3) | 2 (2–2) | 2 (2–2) | 1 |
| Lung injury score | 8.5 (7–10) | 8.5 (5–10) | 8.5 (7–9) | 8 (7–9) | 0.926 |
| Liver | |||||
| Necrosis | 0.5 (0–1) | 0 (0–0) | 1 (0–1) | 0 (0–0) | 0.061 |
| Hepatocellular injury | 2 (2–3) | 1 (1–2) | 2 (2–2) | 1 (1–2) | 0.028 |
| Congestion | 2.5 (2–3) | 2 (1–2) | 2.5 (2–3) | 1 (1–2) | 0.038 |
| Inflammation | 1.5 (1–2) | 1 (0–1) | 2 (1–2) | 0.5 (0–1) | 0.039 |
| Vacuolar degeneration | 3 (2–3) | 1.5 (1–2) | 2 (2–3) | 2 (2–2) | 0.037 |
| Liver injury score | 10 (7–11) | 5 (4–7)*, # | 9 (7–11) | 4.5 (4–7)*, # | 0.016 |
| Spleen | |||||
| Congestion | 1.5 (1–2) | 0.5 (0–1) | 1 (1–2) | 0.5 (0–1) | 0.075 |
| Fibrosis | 0 (0–1) | 0 (0–0) | 0 (0–1) | 0 (0–0) | 0.543 |
| Spleen injury score | 1.5 (1–3) | 0.5 (0–1) | 1 (1–3) | 0.5 (0–1) | 0.079 |
| Kidney | |||||
| Congestion | 1.5 (1–2) | 1 (1–1) | 1 (1–2) | 1 (1–2) | 0.475 |
| Necrosis | 2 (1–3) | 1 (1–2) | 1.5 (1–3) | 2 (2–2) | 0.306 |
| Kidney injury score | 3.5 (2–5) | 2 (2–3) | 2.5 (2–5) | 3 (3–4) | 0.257 |
| Heart | |||||
| Congestion | 1 (0–1) | 0 (0–1) | 0.5 (0–1) | 0 (0–1) | 0.454 |
| Necrosis | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 1 |
| Inflammation | 0 (0–1) | 0 (0––0) | 0.5 (0–1) | 0 (0–0) | 0.238 |
| Heart injury score | 1 (0–2) | 0 (0–1) | 1 (0–2) | 0 (0–0) | 0.177 |
| Muscle | |||||
| Congestion | 1 (0–1) | 0 (0–1) | 0.5 (0–1) | 0 (0–0) | 0.172 |
| Necrosis | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 1 |
| Inflammation | 0 (0–1) | 0 (0–0) | 0 (0–0) | 0 (0–0) | 0.392 |
| Muscle injury score | 1 (0–2) | 0 (0–1) | 0.5 (0–1) | 0 (0–0) | 0.146 |
| Gall bladder | |||||
| Congestion | 1 (0–1) | 1 (0–1) | 1 (1–2) | 1 (0–1) | 0.419 |
| Necrosis | 2 (0–2) | 0.5 (0–1) | 2 (1–2) | 1 (0–1) | 0.023 |
Data are presented as median (minimum–maximum).
(Administration of CoQ10, except the necrosis score, decreased total liver injury scores, total organ injury scores when compared with the equal volume normal saline administration, in the cases of additions both to propofol infusion and sevoflurane inhalation)
CoQ10, coenzyme Q10.
Figure 3.
Light micrographs of the liver, gall bladder, kidney, and urinary bladder after the propofol or sevoflurane exposure with respect to saline or additional CoQ10 therapy (hematoxylin and eosin; 200×). The propofol and sevoflurane organ toxicities were recovered up to different extents with CoQ10 therapy. The desquamated mucosal epithelia recovered in the gall bladder and the urinary bladder with CoQ10 (the second and fourth column light micrographs). The portal inflammation, hepatocytic vacuolation, sinusoidal congestion, and dilatation partially improved with CoQ10 treatment (the first column). The kidney damage, which consisted of mainly vascular congestion and tubular injury, did not change much with the CoQ10 treatment (third column). C, vascular congestion; CoQ10, coenzyme Q10; D, dilatation; E, epithelium; I, inflammation; TI, tubular injury.
Figure 4.
Light micrographs of the spleen, lung, pancreas, and striated muscle (the heart) inset after the propofol or sevoflurane exposure with respect to saline or additional CoQ10 therapy (hematoxylin and eosin; 200×).