Effects of Tanshinone Combined with Western Medicine on Clinical Symptoms and Cardiac Function in Patients with Acute Heart Failure

Liu Fang (劉 芳)

Emergency Department, Wuhan Red Cross Hospital, Wuhan 430010, China.

ABSTRACT

OBJECTIVE: To explore the effects of Tanshinone combined with western medicine on clinical symptoms and cardiac function in patients with acute heart failure. METHODS: The medical records of 96 patients with acute heart failure were randomly divided into 2 groups (48 cases in observation group and 48 cases in control group). The control group was treated with conventional western medicine, and the observation group was treated with Tanshinone IIA sulfonic acid natrium on the basis of western medicine. The traditional Chinese medicine (TCM) syndromes scores before and after treatment (after 28 d of treatment), clinical efficacy, and cardiac echocardiographic indexes and serum biochemical indicators before and after treatment were observed in the 2 groups. RESULTS: After treatment, the scores of TCM syndromes in the 2 groups were significantly decreased (P < 0.05), and the change in observation group was significantly greater than that in control group (P < 0.05). The total clinical effective rate in observation group was significantly higher than that in control group (91.67% vs 75.00%) (P < 0.05). After treatment, the echocardiographic indexes of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) values were significantly reduced in the 2 groups while the left ventricular ejection fraction (LVEF) and stroke volume (SV) value were significantly increased, and the changes in observation group were significantly larger than those in control group (P < 0.05). After treatment, the levels of serum nuclear factor-kappaB (NF-KB), interleukin-1β (IL-1β) and N-terminal pro-brain natriuretic peptide(NT-proBNP) were significantly decreased in the 2 groups (P < 0.05), while the 6-keto-prostaglandin F1α (6-keto-PGF1α) level was significantly increased. And the changes in observation group were significantly greater than those in control group (P < 0.05). CONCLUSION: Tanshinone combined with western medicine can significantly improve the clinical symptoms of patients with acute heart failure, improve cardiac function, reduce the myocardial damage degree, and effectively reduce the risk of short-term recurrence and death, and it has exact clinical efficacy.

KEYWORDS: Acute heart failure; Tanshinone IIA sulfonic acid natrium; Clinical symptoms; Cardiac function

Acute heart failure (AHF) is a common and frequently-occurring disease in clinical internal medicine.It is characterized by urgent onset, rapid development,critical condition, high mortality, etc. The clinical manifestations are mainly decreased ventricular systolic function, impaired ejection function, insufficient cardiac output supply, insufficient blood perfusion in organ tissues, pulmonary circulation and/or systemic circulation congestion, which are the final stages of various heart diseases[1]. The treatment of AHF in modern medicine is mainly based on diuretic, vasodilator and positive inotropic drug, but the overall efficacy of the treatment is not satisfactory. Therefore, it is extremely crucial to seek an effective, safe treatment as well as drug by deeply studying the pathogenesis of AHF[2]. According to the traditional Chinese medicine (TCM), AHF falls into the categories of palpitation, heart impediment,edama, asthma and cough, etc., which mostly are deficiency syndromes. Qi and blood deficiency, yang deficiency, blood stasis and turbid phlegm are the major pathogenesis[3]. Tanshinone which is able to promote blood circulation to remove blood stasis, relieve pain by seductive effects, promoting heart and collateral channels and tranquilize to stop pain, is widely used in cardiovascular diseases[4]. However, it is relatively rare in the treatment of AHF. Therefore, as we discuss Tanshinone combined with western medicine applying to 96 patients with AHF in our hospital, this paper is aimed to provide reference and supplementary data for clinical use, investigating its effect on clinical symptoms and cardiac function of patients. The report is as follows.

DATA AND METHODS

Clinical data

Medical records of 96 patients with AHF admitted to our hospital between July 2015 and July 2017 were collected. Inclusion criteria: Western medicine all refers to the diagnostic criteria for acute left ventricular heart failure in the Guidelines for the Diagnosis and Treatment of Acute Heart Failure (2010)[5]. In accordance with the Guiding Principles for Clinical Research of New Drugs in Traditional Chinese Medicine[6], TCM syndrome classification of heart failure is the patients who are aged 35 to 78 with heart function class III to IV in New York Heart Association (NYHA), over 60 mm left ventricular end-diastolic dimension (LVESD), less than 40% left ventricular ejection fraction (LVEF) and disease duration within 24 h. In line with the Helsinki Declaration, the subjects had signed the relevant informed consent. Exclusion criteria: subjects who had chronic heart failure, pulmonary heart disease, acute right heart failure, cardiogenic shock,heart valve disease, systolic blood pressure of 90 mmHg and under it are excluded. Also, subjects who had heart failure caused by liver and kidney and other multiple organ failure, malignant tumors, acute myocardial infarction with mechanical complications, severe infection which has not been effectively controlled, and contraindications or allergies to this study drug are excluded as well. A total of 96 patients were numbered according to the allocation principle of the random number table method according to the admission order and randomized in a 1: 1 ratio (48 in the observation group and 48 in the control group). There was no statistical difference in the data between the 2 groups (P > 0.05), and the distribution was comparable. See Table 1.

Methods

According to Guidelines for the Diagnosis and Treatment of Acute Heart Failure (2010)[5], the control group was given conventional western medicine, such as oxygen uptake, diuretics, morphine preparations, vasodilators and other conventional drug treatment. Also, accroding to the patient's condition, the control group was given positive inotropic drugs, vasoactive drugs and other drugs to actively treat primary diseases and complications with continuous treatment for 4 weeks. The observation group was treated with Tanshinone IIA sulfonic acid natrium (Shanghai NO.1 Biochemical Pharmaceutical Co., Ltd., National drug approval number: H31022558, Specification: 10 mg) 60 mg + 5% glucose 250 mL on the basis of the above western medicine treatment. Intravenous drip and injection time were controlled at 45 to 60 min, 1 time/d, 7 d for a course of treatment and a total of 4 courses of treatment.

Observation index

① TCM symptom scores: referring to the Guiding Principles for the Clinical Study of New Chinese Medicines[6]on the symptoms of blood stasis, we adopted a four-grade scoring method (0, 2, 4, and 6 points) to assess the severity of symptoms, such as stabbing pain,venous stasis, limb numbness, and scaly dry skin. The higher the score, the more severe the patient-related symptoms, evaluating the changes in symptom scores before and after treatment for 28 days in both groups.② Clinical efficacy evaluation criteria: according to the improvement of cardiac function and symptom scores, the efficacy of the 2 groups was evaluated and divided into three levels which are marked effect(recovery of cardiac function to grade I or improvement of 2 levels, symptom score reduction rate of more than 70%), effective (improvement of cardiac function to 1 level, but not to grade I, symptom score reduction rate within 30% to 70%) and ineffective (no changes in cardiac function grade or even worsening of the disease,symptom score reduction rate of less than 30%). The clinical total effective rate of 2 groups was recorded. ③Echocardiographic indexes: Left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction(LVEF) and stroke volume (SV) were measured by color Doppler ultrasound (Philips, model: iE33) before and 28 days after treatment. ④ Detection of serum biochemical indicators: Before treatment and 28 days of treatment, 2 groups of fasting peripheral blood were collected in the early morning with plasma separating. The supernatant was allowed to stand and refrigerated for examination.Serum levels of nuclear factor-kappa B (NF-KB) and interleukin-1β (IL-1β) were measured by doubleantibody sandwich enzyme-linked immunosorbent assay(ELASA). Amino-terminal B-type brain natriuretic peptide precursor (NT-proBNP) levels were measured by immune-electrochemical luminescence (Roche, model:E60). 6-keto-prostaglandin F1α (6-keto-PGF1α) was detected by radioimmunoassay.

Table 1. Comparison of baseline data between the 2 groups

Statistical methods

The measurement data were expressed in the form ofIndependent sample t-test was used between groups. Paired t-test was used before and 28 days after treatment in the group. Enumeration data were recorded in the form of [n (%)] using χ2test. The rank data were tested by rank sum test and analyzed by SPSS 19.0 software. The test level was α= 0.05. P < 0.05 indicats statistically significant difference.

RESULTS

Comparison of TCM symptom scores and clinical efficacy between 2 groups

The TCM symptom scores before treatment in the observation group and the control group were (35.82 ± 7.25)points and (36.12 ± 7.31) points respectively. The TCM symptom scores after treatment in the observation group and the control group were (16.22 ± 3.74) points and(25.69 ± 5.66) points respectively. There was a statistical difference in the 2 groups before and after treatment and between groups (P < 0.05). After treatment, the clinical total effective rate of the observation group was significantly higher than that of the control group (P < 0.05). See Table 2.

Table 2. Comparison of clinical efficacy in 2 groups [n (%)]

Comparison of echocardiographic indexes between 2 groups before and after treatment

After treatment, the LVEDD and LVESD values were significantly decreased in the 2 groups, and the LVEF and SV values were significantly increased. The changes in the observation group were significantly greater than that in the control group (P < 0.05). See Table 3.

Comparison of serum levels of NF-KB, IL-1β,NT-proBNP, and 6-keto-PGF1α in the 2 groups

After treatment, the serum levels of NF-KB, IL-1β,and NT-proBNP were significantly decreased (P < 0.05), and the level of 6-keto-PGF1α was significantly increased in both groups. The magnitude of change in the observation group was significantly greater than that in the control group (P < 0.05). See Table 4.

Table 3. Comparison of cardiac echocardiographic indexes before and after treatment in 2 groups

Table 3. Comparison of cardiac echocardiographic indexes before and after treatment in 2 groups

Note: aP < 0.05 compared with pre-treatment

Observation group 48 64.82±10.22 52.66±56a 50.36±9.85 42.36±7.69a 40.69±7.72 54.12±9.61a 60.25±10.22 70.12±11.65a Control group 48 65.66±10.18 58.31±9.33a 52.12±10.12 48.33±8.12a 42.31±7.69 49.12±8.28a 58.36±9.98 64.12±10.42a t 0.403 3.092 0.863 3.698 1.030 2.731 0.917 2.660 P 0.688 0.003 0.390 <0.001 0.306 0.008 0.362 0.009

Table 4. Comparison of serum NF-KB, IL-1β, NT-proBNP and 6-keto-PGF1α levels in 2 groups

Table 4. Comparison of serum NF-KB, IL-1β, NT-proBNP and 6-keto-PGF1α levels in 2 groups

Note: aP < 0.05 compared with pre-treatment

Observation group 48 1.22±0.25 0.58±0.08 0.37±0.07 0.17±0.02 5.76±1.02 4.59±0.42 40.22±7.52 68.36±11.25 Control group 48 1.24±0.23 0.76±0.12 0.35±0.06 0.24±0.05 5.82±1.08 5.13±0.69 41.23±7.49 54.15±10.37 t 0.408 8.647 1.503 9.006 0.280 4.632 0.659 6.434 P 0.684 < 0.001 0.136 < 0.001 0.780 < 0.001 0.511 < 0.001

DISCUSSION

AHF is caused by cardiac pump dysfunction which causes a series of clinical syndromes characterized by excessive activation of the neurohumoral system. As the patient's cardiac output decreased, on the one hand it can stimulate the sympathetic nervous system and reninangiotensin-aldosterone system (RAAS) overactivation.Therefore, the overactivation causes contraction of vascular smooth muscle, increased resistance,increased sensitivity of the cardiovascular system to β-adrenoceptor, furthur resulting in acute changes in ventricular load before and after and adrenocortical globular zone lesions and abnormal secretion of aldehydes. On the other hand, decreased cardic output can lead to changes in the structure and function of the vascular endothelium, resulting in endothelium-dependent vasomotor abnormalities and increased arterial resistance,leading to myocardial cell hypoxic-ischemic necrosis and fibrosis. It furthur results in cardiac hypertrophy and ventricular remodeling, thereby aggravating cardiac pump function damage[7]. At the momment, clinical western medicine for AHF mainly includes phosphodiesterase inhibitors, digitalis, and adrenergic drugs. Although it can effectively relieve the clinical symptoms of patients in the short term, it has poor long-term results.

Chinese medicine believes that heart failure can be commensurate with heart palpitations and other disease names. Its causes are nothing more than invasion of the body by external pathogenic factors, emotionally internal injuries, prolonged heart disease, injury to vitality, and disorders of the organs, etc. That leads to deficiency of both the qi and blood, deficiency of yang qi, and blood stasis by phlegn, which are syndromes of deficiency in nature and deficiency in superficiality as well as simutaneous occurrence of deficiency and excess[8].The deficiency in nature is mainly due to yang deficiency, qi deficiency and yin deficiency. Deficiency in superficiality is mainly marked by blood stasis, retention of phlegm and morbid fluid, and stagnation of dampness. The heart failure patients have declined qi of the zang-organ, with the phlegm blocking the chest because yang deficiency which is unable to resolve body fluid and generate phlegm as well as qi stagnation in the throat. Phlegm obstructs yang in the chest, with the blood line blocking.Then the blood stasis is develped. The phlegm and stasis obstruct the Heart Merdian causing heart impediment.Salvia miltiorrhiza has a high value in traditional Chinese medicine and its root has high medical value. It is rich in Tanshinone and can have the effect of removing stasis,refreshing, promoting blood circulation, and removing impediment. It also treats insomia by palpation with fear,painful chest and abdomen, and so on for the effects of reflenishing the heart and calming the mind, relieving the mental stress, and promoting heart and collateral channels[9]. Tanshinone belongs to a class of fat-soluble terpenoid natural products, of which sodium Tanshinone IIA sulfonate has been widely used in clinical practice.Tanshinone has the activity of promoting the metabolism of biological organisms and various biochemical reactions.Alongside that, it has significant therapeutic effects on cardiovascular diseases, can significantly improve the physical and chemical properties of blood flow in biological organisms, and has no obvious drug toxicity to liver and kidney[10].In this article, Tanshinone IIA sodium sulfonate combined with western medicine was used in the treatment of 48 patients with AHF in our hospital. It was found that the TCM symptom scores were significantly reduced, and the total clinical effective rate was significantly higher than that of the other 48 patients treated with western medicine alone. This shows that the above combination of Chinese and Western medicine can improve the clinical symptoms of AHF, and the curative effect is definite which is consistent with that reported by Wang Xi[11].

The results of this study show that the LVEDD and LVESD values decreased with increased the LVEF and SV values after 28 days of treatment in the observation group. The improvement effect was better than that of the control group, which suggested that Tanshinone IIA sulfonic acid natrium combined with western medicine could significantly improve cardiac function in patients with AHF. During the occurrence and development of heart failure, myocardial cells are in a state of ischemia and hypoxia for a long time, which can produce active O2 and further activate nuclear factor-KB (NF-KB). Then myocardial cells induce inflammatory factors, causing a cascade of inflammatory factors and exerbation of heart failure[12]. NF-KB is a protein with an important transcriptional activation effect mainly produced by the activation and degradation of IκB kinase stimulated by inflammatory stimuli, which belongs to the typical inflammatory markers. High levels of IL-1β can affect the regulation of cardiomyocyte apoptosis and enhance the damage of cardiac target organ effects, resulting in low cardiac pump function and promote myocardial fibrosis. Then this kind of protein result in remodeling of the interstitium[13]. Li Chaoliang[14]and others studied patients for heart failure and found that NT-proBNP levels in the patient's body increased significantly with the worsening of heart failure symptoms, while 6-keto-PGF1α levels decreased significantly. NT-proBNP is currently recognized as a valuable diagnostic marker for heart failure,and its high level predicts increased progression of heart failure and poor prognosis[15]. However, 6-keto-PGF1α is a stable metabolite secreted by vascular endothelial cells,and its reduced level can indirectly reflect the dysfunction and damage of vascular endothelial cells[16]. In this study,the serum levels of NF-KB, IL-1β, and NT-proBNP in the observation group decreased after 28 days of treatment, while the level of 6-keto-PGF1α increased.The improvement was stronger than that of the control group. It can be further confirmed that TanshinoneIIA sodium sulfonate can improve cardiac function in patients with AHF and it effectively delay or improve myocardial fibrosis and ventricular remodeling.

In summary, Tanshinone IIA sulfonic acid natrium combined with western medicine can significantly improve the clinical symptoms of patients with AHF, such as improving cardiac function, reducing myocardial cell damage and delaying ventricular remodeling, which has significant clinical application value.