<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article  PUBLIC "-//NLM//DTD Journal Publishing DTD v3.0 20080202//EN" "http://dtd.nlm.nih.gov/publishing/3.0/journalpublishing3.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="3.0" xml:lang="en" article-type="research article"><front><journal-meta><journal-id journal-id-type="publisher-id">JBM</journal-id><journal-title-group><journal-title>Journal of Biosciences and Medicines</journal-title></journal-title-group><issn pub-type="epub">2327-5081</issn><publisher><publisher-name>Scientific Research Publishing</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.4236/jbm.2021.95008</article-id><article-id pub-id-type="publisher-id">JBM-109329</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biomedical&amp;Life Sciences</subject></subj-group></article-categories><title-group><article-title>
 
 
  Research on Applications of Shenmai Injection on Hypertensive ICH Combined with Cerebrocardiac Syndromes
 
</article-title></title-group><contrib-group><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gang</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Jianju</surname><given-names>Feng</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Shaojun</surname><given-names>Yang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Junjie</surname><given-names>Lv</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Donghai</surname><given-names>Yuan</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Chenbing</surname><given-names>Wang</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Feng</surname><given-names>Ding</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Chao</surname><given-names>Gu</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author" xlink:type="simple"><name name-style="western"><surname>Gaofeng</surname><given-names>Shao</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff2"><addr-line>Radiology Department, Zhuji Affiliated Hospital of Shaoxing University, Shaoxing, China</addr-line></aff><aff id="aff1"><addr-line>Department of Neurosurgery, Zhuji Affiliated Hospital of Shaoxing University, Shaoxing, China</addr-line></aff><pub-date pub-type="epub"><day>06</day><month>05</month><year>2021</year></pub-date><volume>09</volume><issue>05</issue><fpage>79</fpage><lpage>85</lpage><history><date date-type="received"><day>29,</day>	<month>April</month>	<year>2021</year></date><date date-type="rev-recd"><day>23,</day>	<month>May</month>	<year>2021</year>	</date><date date-type="accepted"><day>26,</day>	<month>May</month>	<year>2021</year></date></history><permissions><copyright-statement>&#169; Copyright  2014 by authors and Scientific Research Publishing Inc. </copyright-statement><copyright-year>2014</copyright-year><license><license-p>This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/</license-p></license></permissions><abstract><p>
 
 
  Objective: This study is to observe the therapeutic effects of Shenmai injection on patients with hypertensive ICH and cerebrocardiac syndromes as well as its effects on prognosis. 
  Methods: A total of 72 patients with severe hypertensive ICH and cerebrocardiac syndromes were selected and divided into the control group and the experimental group (Shenmai injection group) randomly, 36 patients in each group. The control group was treated by conventional therapy, while the experimental group was administrated by intravenous drip of the mixture of 50 ml Shenmai injection and 250 ml 5% glucose injection based on the treatment of the control group, once everyday, 2 weeks continuously. 
  Results: Myocardial enzyme indexes of two groups at 3d, 7d and 14d were observed (Table 1). Myocardial enzyme index of the experimental group was improved quickly and significantly. Myocardial enzyme data of two groups at 3d, 7d and 14d were P &lt; 0.05. According to the electrocardiographic examinations results, ECG anomalies of the experimental group at 7d and 14d were also improved quickly (P &lt; 0.05). There are no evident anomalies in GCS scores of two groups at 7d, but GCS score of the experimental group at 14d of the medication was significantly higher than that of the control group (P &lt; 0.05). 
  Conclusions: Shenmai injection has some therapeutic effects on cerebral injuries and myocardial damages. It can treat brain and heart simultaneously, realize the goal of addressing both symptoms and root causes, and improve prognosis of patients with severe hypertensive ICH.
 
</p></abstract><kwd-group><kwd>Hypertensive ICH</kwd><kwd> Cerebrocardiac Syndromes</kwd><kwd> Shenmai Injection</kwd></kwd-group></article-meta></front><body><sec id="s1"><title>1. Introduction</title><p>Intracerebral hemorrhage (ICH) can threaten life and physical health of the aged group seriously due to its high morbidity, high fatality rate and high disability rate in clinics. Moreover, most survivors have different degrees of dysneuria. ICH brings heavy life and psychological burdens to the society, family and the patients. Cerebrocardiac syndromes are clinical syndromes which are developed upon cardiac dysfunction or myocardial disorder caused by serious diseases of central nervous system, and they are also called brain-derived cardiovascular dysfunction. Cerebrocardiac syndromes are similar with acute myocardial infarction (MI) or myocardial ischemia and arrhythmia. There are mutual influences and crosslinking relations between heart and brain. So far, there’s no systematic therapeutic method. Only few studies on the combination of severe hypertensive ICH and cerebrocardiac syndromes have been reported in China. It has not attracted enough attentions in clinics, accompanied with high rate of missed diagnosis and misdiagnosis rate. Moreover, most antiarrhythmic drugs have poor therapeutic effects to cerebrocardiac syndromes. It is difficult to treat cerebrocardiac syndromes. Based on conventional western drug therapy, our hospital applies Shenmai injection to treat patients with severe hypertensive ICH and cerebrocardiac syndromes, which has achieved outstanding therapeutic effect. Results are summarized in the following test.</p></sec><sec id="s2"><title>2. Methodology</title><sec id="s2_1"><title>2.1. Research Objects</title><p>A total of 71 patients with severe hypertensive ICH and cerebrocardiac syndromes in the Neurosurgery Department of our hospital were selected and divided into the control group and the experimental group (Shenmai injection group) randomly. This study was approved by the Ethics Committee of the hospital and all patients have submitted a written informed consent.</p></sec><sec id="s2_2"><title>2.2. Inclusion and Exclusion Standards</title><p>Inclusion standards: 1) history of hypertension, GCS score &lt; 12, aged between 50 - 85. 2) typical hypertensive ICH positions; 3) conforming to diagnosis standards of cerebrocardiac syndromes, including a series of symptoms of arrhythmia, myocardial ischemia, cardiac insufficiency and acute myocardial infarction, abnormal myocardial enzyme spectra and ECG changes.</p><p>Exclusion standards: 1) brain cavernous hemangioma, aneurysmal hemorrhage and tumor bleeding; 2) history of heart diseases like coronary heart disease and arrhythmia, extremely instable basic vital signs, severe heart, lung, liver and kidney diseases; 3) having allergies or serious adverse reactions to ingredients and accessories of Shenmai injection, having family allergy history to drugs and allergic physiques.</p></sec><sec id="s2_3"><title>2.3. Treatment Methods</title><p>Both groups adopt conventional treatments, including dehydration-based reduction of intracranial pressure, anti-infection and nutrition support. Patients with severe arrhythmia were administrated by propranolol and patients who have complications of heart failure were administrated by deslanoside and dobutamine. Surgical treatment was adopted to patients who had indications of operation. Based on the conventional treatment, the experimental group was provided with Shenmai injection (Zhengda Qingchunbao Group) additionally. Shenmai injection (50 ml) was added into 250 ml 5% glucose injection, which was given through intravenous drip once every day, 2 weeks continuously.</p></sec><sec id="s2_4"><title>2.4. Index Observation Test</title><p>Both groups attended in the conventional vital sign and electrocardiogram monitoring. At 6d of hospitalization, myocardial enzyme spectra and troponin were tested. Moreover, myocardial enzyme spectra, including aspartic aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and isozymes (CK-MB), were reexamined at 3d, 7d and 14d. All patients had 24 h electrocardiogram monitoring immediately after the hospitalization and ECG examination was performed upon the discovery of any anomalies. ECG examinations and GCS scores were performed at 7d and 14d after the hospitalization.</p></sec><sec id="s2_5"><title>2.5. Statistical Process</title><p>The Statistical Program for Social Sciences software18.0 (SPSS 18.0) was applied. Measurement data was expressed by mean &#177; standard deviation. The inter-group comparison used the two independent sample t-test and intragroup comparison before and after the treatment used the pairwise t-test. Inter-group comparison of enumeration data used the x2 test. P &lt; 0.05 indicates that the difference has statistical significance.</p></sec></sec><sec id="s3"><title>3. Results</title><p>A total of 72 patients with severe hypertensive ICH who have been hospitalized in our hospital from January, 2020 to December, 2020 were chosen and divided into the control group and experimental group (Shenmai injection group) randomly, 36 cases in each group. After exclusion of patients, the control group had 31 cases and the experimental group had 30 cases. The control group was composed of 18 males and 14 females who were aged between 51 - 81, averaging at (63.81 &#177; 9.32) years old. The experimental group had 17 males and 13 females who were aged between 50 - 79, averaging at (64.84 &#177; 9.41) years old. Two groups have no significant differences in term of general conditions, CT scanning of bleeding position and volume of bleeding (P &gt; 0.05). This research scheme was approved by the Ethics Committee of our hospital and all patients signed the informed consent.</p><p>Myocardial enzyme indexes of two groups at 3d, 7d and 14d were observed (<xref ref-type="table" rid="table1">Table 1</xref>). Myocardial enzyme index of the experimental group was improved quickly and significantly. Myocardial enzyme data of two groups at 3d, 7d and 14d were P &lt; 0.05. According to the electrocardiographic examinations results (<xref ref-type="table" rid="table2">Table 2</xref>), ECG anomalies of the experimental group at 7d and 14d were also improved quickly (P &lt; 0.05). It can be seen from <xref ref-type="table" rid="table3">Table 3</xref> that there’s no evident anomalies in GCS scores of two groups at 7d, but GCS score of the experimental group at 14d of the medication was significantly higher than that of the control group (P &lt; 0.05).</p></sec><sec id="s4"><title>4. Discussions</title><p>As a sever acute disease with high incidence rate in clinics, hypertensive ICH has clinical characteristics of sudden onset, quick progression, high fatality rate and poor prognosis. In China, the number of patients with ICH is increasing in the continuous aging process. Cardiovascular and cerebrovascular diseases have become the top 1 cause of death. Cerebrocardiac syndromes refer to a series of signs, symptoms, myocardial enzyme spectra anomalies and ECG changes similar with arrhythmia, myocardial ischemia, cardiac insufficiency and acute myocardial infarction caused by acute cerebrovascular accidents. Clinical symptoms of patients with cerebrocardiac syndromes include quick progress, sudden onset and high mortality. Cerebrocardiac syndromes will threaten life safety of patients significantly if they are not treated timely.</p><p>Patients with acute cerebrovascular diseases often are accompanied with cerebrocardiac syndromes. It is reported that the incidence rate of acute cerebrovascular</p><table-wrap id="table1" ><label><xref ref-type="table" rid="table1">Table 1</xref></label><caption><title> Myocardial enzyme spectra test results</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >(cases)</th><th align="center" valign="middle" >CK (U/L)</th><th align="center" valign="middle" >CK-MB (U/L)</th><th align="center" valign="middle" >AST (U/L)</th><th align="center" valign="middle" >LDH (U/L)</th></tr></thead><tr><td align="center" valign="middle" >Experimental group N = 30</td><td align="center" valign="middle" >3d 7d 14d</td><td align="center" valign="middle" >546 &#177; 87 234 &#177; 63 82 &#177; 23</td><td align="center" valign="middle" >182 &#177; 59 81 &#177; 32 36 &#177; 23</td><td align="center" valign="middle" >73 &#177; 23 43 &#177; 12 28 &#177; 6</td><td align="center" valign="middle" >443 &#177; 79 279 &#177; 43 84 &#177; 23</td></tr><tr><td align="center" valign="middle" >Control group N = 32</td><td align="center" valign="middle" >3d 7d 14d</td><td align="center" valign="middle" >732 &#177; 123 432 &#177; 82 133 &#177; 35</td><td align="center" valign="middle" >232 &#177; 89 134 &#177; 79 56 &#177; 28</td><td align="center" valign="middle" >121 &#177; 48 68 &#177; 17 33 &#177; 8</td><td align="center" valign="middle" >632 &#177; 112 354 &#177; 67 112 &#177; 42</td></tr></tbody></table></table-wrap><table-wrap id="table2" ><label><xref ref-type="table" rid="table2">Table 2</xref></label><caption><title> ECG examination results</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >(cases)</th><th align="center" valign="middle" >EKG recovers to normal at 7d (cases)</th><th align="center" valign="middle" >EKG recovers to normal at 14d (cases)</th></tr></thead><tr><td align="center" valign="middle" >Experimental group</td><td align="center" valign="middle" >30</td><td align="center" valign="middle" >18</td><td align="center" valign="middle" >28</td></tr><tr><td align="center" valign="middle" >Control group</td><td align="center" valign="middle" >32</td><td align="center" valign="middle" >11</td><td align="center" valign="middle" >21</td></tr><tr><td align="center" valign="middle" >P-value</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >&lt;0.05</td><td align="center" valign="middle" >&lt;0.05</td></tr></tbody></table></table-wrap><table-wrap id="table3" ><label><xref ref-type="table" rid="table3">Table 3</xref></label><caption><title> GCS scores</title></caption><table><tbody><thead><tr><th align="center" valign="middle" ></th><th align="center" valign="middle" >(Cases)</th><th align="center" valign="middle" >GCS score at 7d</th><th align="center" valign="middle" >GCS score at 14d</th></tr></thead><tr><td align="center" valign="middle" >Experimental group</td><td align="center" valign="middle" >30</td><td align="center" valign="middle" >10.56 &#177; 1.43</td><td align="center" valign="middle" >12.89 &#177; 1.53</td></tr><tr><td align="center" valign="middle" >Control group</td><td align="center" valign="middle" >32</td><td align="center" valign="middle" >10.86 &#177; 1.53</td><td align="center" valign="middle" >11.36 &#177; 1.65</td></tr><tr><td align="center" valign="middle" >P value</td><td align="center" valign="middle" ></td><td align="center" valign="middle" >&gt;0.05</td><td align="center" valign="middle" >&lt;0.05</td></tr></tbody></table></table-wrap><p>diseases is about 80%. Clinically, the rate of missed diagnosis and misdiagnosis rate are relatively high. The superposition of acute cerebrovascular diseases and cerebrocardiac syndromes can aggravate the disease condition of patients, increase difficulties in treatment and affect prognosis significantly [<xref ref-type="bibr" rid="scirp.109329-ref1">1</xref>] - [<xref ref-type="bibr" rid="scirp.109329-ref6">6</xref>]. Treatment of severe hypertensive ICH must consider general circulation and brain circulation simultaneously. The clinical applications of Shenmai injection give us a good choice to realize brain-heart simultaneous treatment, address symptoms and root causes and improve prognosis.</p><p>Shenmai injection was derived from Shendong decoction in the Zhen Yin Mai Zhi. It is mainly prepared by Ginseng and Radix Ophiopogonis. It can nourish Yin and generate body fluid, tonify Qi and activate pulses. Shenmai injection is applicable to various shocks. It can excite interrenal system, increase elimination of various pathologic substances of the reticuloendothelial system (RES) during stroke, improve blood supply of important organs like heart, liver and brain, improve micro-circulation and anti-coagulation, strengthen heart and increase pressure, improve coronary flow, increase resistance to anoxia of body, decrease myocardial oxygen consumption, protect and repair myocardial cells and has certain anti-arrhythmia. Clinically, Shenmai injection is mainly applied to treat cardiovascular and cerebrovascular diseases [<xref ref-type="bibr" rid="scirp.109329-ref7">7</xref>].</p><p>According to modern pharmacological research, Shenmai injection can: 1) eliminate harmful substances like oxygen free radicals and proto-oncogene, inhibit calcium overload, improve blood circulation, promote synthesis of proteins and neurotransmitter in brains, and stop cells to initiate suicide program; 2) decrease apoptosis [<xref ref-type="bibr" rid="scirp.109329-ref8">8</xref>]; 3) inhibit endogenous nitric oxide synthase (NOS), relieve vasogenic edema, relieve inflammatory reactions, promote hematoma absorption, and strengthen immunity of the body [<xref ref-type="bibr" rid="scirp.109329-ref9">9</xref>] [<xref ref-type="bibr" rid="scirp.109329-ref10">10</xref>]. Shenmai injection can lower expression of tumor necrosis factor-a (TNF-A) in ischemic zone surrounding the hematoma, and inhibit expression of interleukin (IL-6) and proteolytic enzymes. Besides, it can increase expression of HSP70 in ischemic zone surrounding the hematoma and stop thrombosis and endothelia injury caused by inflammations, thus enabling to protect nerves [<xref ref-type="bibr" rid="scirp.109329-ref11">11</xref>].</p><p>Shenmai injection can protect myocardial damages of patients after carido-pulmonary resuscitation to some extent. The modern pharmacological studies have found that the relevant mechanism might be related with anti-lipid peroxidation, increased activity of superoxide dismutase of cardiac muscle tissues, decreased levels of CK-MB, cardiac troponin T (cTnT) and N-terminal B-type natriuretic peptide precursor (NT-proBNP), and improved left ventricular ejection fraction (LVEF), stroke volume (SV) and cardiac output (CO) [<xref ref-type="bibr" rid="scirp.109329-ref12">12</xref>] [<xref ref-type="bibr" rid="scirp.109329-ref13">13</xref>] [<xref ref-type="bibr" rid="scirp.109329-ref14">14</xref>] [<xref ref-type="bibr" rid="scirp.109329-ref15">15</xref>].</p><p>Myocardial enzyme indexes of two groups at 3d, 7d and 14d were observed. It found that the myocardial enzyme index of the experimental group was improved quickly and significantly. Myocardial enzyme data of two groups at 3d, 7d and 14d were P &lt; 0.05. According to the electrocardiographic examinations results, ECG anomalies of the experimental group at 7d and 14d were also improved quickly (P &lt; 0.05). There are no evident anomalies in GCS scores of two groups at 7d, but GCS score of the experimental group at 14d of the medication was significantly higher than that of the control group (P &lt; 0.05).</p><p>According to pharmacological and experimental studies, Shenmai injection has certain therapeutic effects to cerebral injuries and myocardial damages. It can improve microcirculation disturbance surrounding the hematoma and accelerate absorption of hematoma, which are beneficial to recovery of neurological functions and improve clinical therapeutic effect of rehabilitation patients.</p><p>On one hand, Shenmai injection to patients with severe hypertensive ICH and cerebrocardiac syndromes in the early stage can make full use of essence of Traditional Chinese Medicine. On the other hand, it can treat brain and heart diseases simultaneously, and realize the goal of addressing both symptoms and root causes. This is expected to improve prognosis of patients with severe hypertensive ICH and it shall be further studied.</p></sec><sec id="s5"><title>Fund-Supported Projects</title><p>Zhejiang Medical Association Clinical research fund projects 2019ZYC-A157.</p><p>Shaoxing Health Science and technology plan 2017CX025.</p><p>Zhejiang Health Development Foundation 2019ZD059.</p><p>Zhejiang Health Development Foundation 2019ZA127.</p></sec><sec id="s6"><title>Conflicts of Interest</title><p>The authors declare no conflicts of interest regarding the publication of this paper.</p></sec><sec id="s7"><title>Cite this paper</title><p>Yang, G., Feng, J.J., Yang, S.J., Lv, J.J., Yuan, D.H., Wang, C.B., Ding, F., Gu, C. and Shao, G.F. (2021) Research on Applications of Shenmai Injection on Hypertensive ICH Combined with Cerebrocardiac Syndromes. 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