To explore the protective effects of Danhong injection against cerebral damage during on-pump coronary artery bypass graft surgery and its mechanism.
The protection of vital organs against damage during cardiopulmonary bypass (CPB) cardiac surgery is a must thing for any health professional. It has been reported that there is damage induced by ischemia reperfusion during on-pump coronary artery bypass graft surgery [
Fifty patients aged 50–75 years, who met the following criteria, were recruited for on-pump coronary artery bypass grafting. The criteria are no histories of endocarditis, nervous system disease, immune system disease, or mental disorder; absence of abnormal function of lung, liver, or kidney; presentation of normal hemoglobin level, electrolyte concentration, and blood gas analysis results; presentation of cardiac function of grades II-III (categorization according to the New York Heart Association Functional Classification); and no use of drugs that may affect the central nerve system. These eligible subjects were randomly divided into Danhong injection group (group D) and control group (group C) with 25 patients in each group.
Patients fasted for 12 hrs prior to the operation and their fluid intake was forbidden for 4 h. Anesthesia was induced with intramuscular administration of sodium (0.1 g) and scopolamine (0.3 mg) and intravenous administration of midazolam (0.1 mg·kg−1), fentanyl (10–20
To evaluate the effects of Danhong injection, group D was given Danhong injection at the dose of 1.5 mL·kg−1, while group C was given the same volume of normal saline when the artery was cut open.
Jugular bulb blood of each patient was collected at four time points including the following: right before the operation began (T1), when body temperature rewarming to 36°C (T2), 30 min after the termination of cardiopulmonary bypass (CPB) (T3), and 6 h after the termination of CPB (T4). The collected blood was used for the evaluation of superoxide dismutase (SOD) activity by xanthine oxidase method, concentration determination of malondialdehyde (MDA) by thiobarbital method, detection of TNF-
Data were analyzed using SPSS-11.0 statistical software and measurement data were presented as mean ± standard deviation. Comparison between both groups was treated with two-factor analysis of variance, and
No significant difference regarding age, gender, weight, length of CPB time, aortic clamp time, and operative time or blood gas analysis results between the two groups was found (
The clinical and demographic characteristics of patients.
Parameter | Group D | Group C |
---|---|---|
Age | 60.2 ± 3.6 | 59.7 ± 2.8 |
Gender (male/female) | 1 : 1.05 | 1 : 1.09 |
Weight | 62.2 ± 5.9 | 61.8 ± 4.6 |
Length of CPB time | 71.7 ± 5.6 | 72.1 ± 6.3 |
Aortic clamp time | 33.5 ± 2.0 | 32.1 ± 1.9 |
MDA concentration and SOD activity comparison was shown in Table
MDA concentration and SOD activity comparison at four time points (
Parameter | Group | T1 | T2 | T3 | T4 |
---|---|---|---|---|---|
SOD (NU/mL) | C | 80.2 ± 5.6 | 71.9 ± 3.1 |
70.4 ± 4.2 |
69.8 ± 3.3 |
D | 81.9 ± 4.8 | 80.2 ± 6.7ΔΔ | 81.6 ± 4.5ΔΔ | 74.8 ± 4.9Δ | |
|
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MDA (mol/L) | C | 4.69 ± 0.62 | 6.98 ± 0.37 |
7.26 ± 0.28 |
6.62 ± 0.41 |
D | 4.76 ± 0.48 | 6.02 ± 0.46 |
6.51 ± 0.44 |
6.13 ± 0.28 |
Comparing with T1 within group C,
Comparison of TNF-
Comparison of TNF-
Parameter | Group | T1 | T2 | T3 | T4 |
---|---|---|---|---|---|
TNF- |
C | 20 ± 4 | 24 ± 6 | 39 ± 5 |
32 ± 3 |
D | 19 ± 5 | 22 ± 4 | 30 ± 4 |
25 ± 6 | |
|
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IL-6 (pg/mL) | C | 91 ± 18 | 108 ± 26 | 230 ± 25 |
220 ± 28 |
D | 84 ± 12 | 95 ± 21 | 200 ± 17 |
171 ± 29 | |
|
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IL-8 (ng/mL) | C | 0.99 ± 0.24 | 1.12 ± 0.25 | 2.38 ± 0.17 |
2.61 ± 0.54 |
D | 0.95 ± 0.29 | 1.06 ± 0.27 | 2.09 ± 0.22 |
2.23 ± 0.17 | |
|
|||||
IL-10 (ng/mL) | C | 27 ± 4 | 59 ± 11 | 230 ± 31 |
133 ± 26 |
D | 26 ± 3 | 47 ± 16 | 238 ± 56 |
172 ± 32 |
Comparing with T1 within group C,
The correlation of SOD, MDA, TNF-
The correlation of SOD, MDA, TNF-
SOD | MDA | TNF- |
IL-6 | IL-8 | IL-10 | |
---|---|---|---|---|---|---|
SOD | 1 | 0.25 | 0.30 | 0.19 | 0.41 | 0.07 |
MDA | 1 | 0.13 | 0.17 | 0.10 | 0.21 | |
TNF- |
1 | 0.25 | 0.38 | 0.09 | ||
IL-6 | 1 | 0.19 | 0.12 | |||
IL-8 | 1 | 0.36 | ||||
IL-10 | 1 |
It has been reported that cerebral damage during CPB surgery is related to inflammatory response [
During inflammatory processes, endothelial cells become activated and expression of adhesion molecules is increased in response to inflammatory cytokines leading to aggregation of large number of white blood cells, which can contribute to cerebral microcirculatory disturbance through mechanical obstruction and vascular dilatation, resulting in cerebral hypoxia and ischemia. On the other hand, white blood cells aggregation can also induce damage to brain cells and blood brain barrier by releasing toxins like free oxygen radicals, proteolytic enzymes, lysosomal enzymes, and excitatory amino acid [
Danhong injection mainly consists of Chinese herbs Danshen and Honghua. It is used for treating coronary heart disease, angina, hypertension, thrombosis, and other cardiovascular diseases and has significant therapeutic effects on acute cerebral infarction [
Till now, most studies on Danshen were focused on its function of lipid peroxidation, endothelial cell protection, and regulation of lipid and smooth muscle cells, while relevant researches about its effects on inhibiting infiltration of inflammatory cells and expression of immune factors were few. In this study, protective effects of SOD are enzymes that alternately catalyze the dismutation (or partitioning) of the superoxide (
IL-8 may induce NGF production in vivo after brain injury. This hypothesis is also supported by the findings that astrocytes and microglia express the IL-8 receptor, and therefore these cells are likely candidates for the production of NGF following the challenge with IL-8. In addition, IL-8 has been shown to promote the survival of hippocampal neurons possibly through the release of factors by astrocytes that were present in these cultures. It cannot be excluded for the release of these factors. Therefore, to elucidate whether IL-8 induces NGF production in astrocytes, CSF samples of brain-injured patients containing IL-8 were incubated with purified astrocyte cultures derived from newborn mouse brain. NGF production was induced by all samples, except for one containing low levels of IL-8, and the NGF levels appeared to depend on the concentration of IL-8. When CSF samples were pretreated with anti-IL-8 antibodies, a distinct but not complete inhibition of the astrocytic NGF production occurred, indicating that IL-8 may act in association with other factors/cytokines. For this purpose, the CSF samples utilized for the culture experiments were tested for other cytokines. IL-6 and TNF-
Chinese medicinal Danhon injection includes multiple chemicals. In the future, our work is to find the specified compound mechanism of the cerebral damage which is important.
All of the results in this study belong to the authors. The authors declare that they have no conflict of interests.