Search

In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.

The 21st century is a highly information-driven era, and traditional Chinese medicine(TCM) pharmacy is also moving towards digitization and informatization. New technologies such as artificial intelligence and big data with information technology as the core are being integrated into various aspects of drug research, manufacturing, evaluation, and application, promoting interaction between these stages and improving the quality and efficiency of TCM preparations. This, in turn, provides better healthcare services to the general population. The deep integration of emerging technologies such as artificial intelligence, big data, and cloud computing with the TCM pharmaceutical industry will innovate TCM pharmaceutical technology, accelerate the research and industrialization process of TCM pharmacy, provide cutting-edge technological support to the global scientific community, boost the efficiency of the TCM industry, and promote economic and social development. Drawing from recent developments in TCM pharmacy in China, this paper discussed the current research status and future trends in digital TCM pharmacy, aiming to provide a reference for future research in this field.

Jiuzhuan Huangjing Pills (JHP) composed of Polygonati Rhizoma (PR) and Angelicae Sinensis Radix (ASR) remedied mitochondria to cure metabolic dysfunction-associated fatty liver disease (MAFLD). However, a comparison of the anti-MAFLD ability between JHP prescription and PR and ASR single-medicines in MAFLD has not been performed, and the action mechanisms and substances remain unknown. Our results show that JHP, PR and ASR decreased serum and liver lipid levels. The effects of JHP were stronger than those of PR and ASR. JHP, PR and ASR afforded protection to mitochondrial ultrastructure, and regulated oxidative stress and energy metabolism in mitochondria. JHP also regulated the expression of β-oxidation genes, which were not regulated by PR and ASR. JHP-, PR- and ASR-derived components in mitochondrial extracts regulated oxidative stress, energy metabolism, and β-oxidation gene expression and alleviated cellular steatosis. Four, six and eleven compounds were identified in mitochondrial extracts from PR-, ASR- and JHP-treated rats, respectively. The data suggest that JHP, PR and ASR alleviated MAFLD by remedying mitochondria, while the ability of JHP was stronger than that of PR and ASR, which was involved with the β-oxidation promotion. The compounds identified may be the main ingredients in the three extracts active in MAFLD improvement., Competing Interests: Conflict of interest statement The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.

Ethnopharmacological Relevance: Fufang Zhenzhu Tiaozhi capsule (FTZ) is a patented preparation of Chinese herbal medicine that has been used to treat hyperlipidemia, nonalcoholic fatty liver disease, atherosclerosis, and other glucolipid metabolic diseases (GLMDs) in the clinic for almost 10 years. However, how FTZ reduces albuminuria and attenuates diabetic kidney disease (DKD) progression is unknown., Aim of the Study: To clarify the effects of FTZ on DKD mice model and to explore the underlying mechanisms., Materials and Methods: We used streptozotocin (STZ) (40 mg/kg/d, i.p. for 5 days, consecutively) combined with a high-fat diet (HFD) to induce a DKD mouse model, followed by FTZ (1, 2 g/kg/d, i.g.) treatment for 12 weeks. Losartan (30 mg/kg/d, i.g.) was used as a positive control. Measurements of 24 h proteinuria, serum creatinine (SCr), fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), and low density lipoprotein cholesterol (LDL-C) levels and expression levels of fibronectin (FN), collagen IV, inflammatory cytokines, inflammatory cells, interleukin-17A (IL-17A) and the nuclear transcription factor-κB (NF-κB) signaling pathway in the kidney were examined., Results: FTZ effectively decreased 24 h proteinuria, Scr, FBG, TC, TG, and LDL-C levels, inhibited mesangial cell expansion, reduced FN and collagen IV accumulation, and F4/80 + macrophage cell infiltration and Ly-6G + neutrophil infiltration in glomerulus and tubulointerstitium. Furthermore, IL-17A production and the NF-κB signaling pathway were also downregulated after the administration of FTZ., Conclusion: FTZ might attenuate DKD progression, and inhibited kidney inflammation and fibrosis by inhibiting the expression of RORγT and IL-17A in vivo, offering novel insights for the clinical application of FTZ., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Long-term muscle fatigue is a major cause of injury. Drugs/nutrients from herbal medicines that prevent fatigue remain a major research focus. In China, a prescription composed of Polygonati Rhizoma and Notoginseng Radix et Rhizoma has been commonly used as a herb and food nutrient, providing protection against fatigue in the clinic. To date, the mechanisms through which this prescription prevented fatigue are unknown. Here, we identified the effects of this prescription on muscle fatigue based on energy and oxidation regulation. Fatigue mouse models were produced through weight-bearing exhaustive swimming. Mice were intragastrically administered prescription extracts (1 and 2 g/kg) for four weeks. Changes in exhaustive swimming times, antifatigue biochemical indicators, oxidative status, and energy metabolism were investigated. The prescription prolonged the exhaustive swimming time of the mice. The content of lactic acid and blood urea nitrogen in the serum was also markedly reduced by the prescription. The content of liver glycogen and lactate dehydrogenase in the serum increased. The prescription also significantly reduced malondialdehyde levels and increased the levels of superoxide dismutase and glutathione peroxidase. The levels of ATPase, complexes I and II in the mitochondria of hind-leg skeletal muscle, and serum creatine kinase also increased in response to the prescription. Our results indicated that the prescription could effectively alleviate muscle fatigue status by promoting energy metabolism and antioxidation ability. The prescription therefore represents a useful drug/nutrient strategy to alleviate muscle fatigue., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2020 Ya-Qin Yang et al.)

Ethnopharmacological Relevance: Standard therapy for asthma, a highly heterogeneous disease, is primarily based on bronchodilators and immunosuppressive drugs, which confer short-term symptomatic relief but not a cure. It is difficult to discover novel bronchodilators, although potential new targets are emerging. Traditional Chinese Medicine (TCM) formulas have been used to treat asthma for more than 2000 years, forming the basis for representative asthma treatments., Aim of the Study: Based on the efficacy of TCM formulas, anti-asthmatic herbal compounds bind proteins are potential targets for asthma therapy. This analysis will provide new drug targets and discovery strategies for asthma therapy., Materials and Methods: A list of candidate herbs for asthma was selected from the classical formulas (CFs) of TCM for the treatment of wheezing or dyspnea recorded in Treatise on Cold Damage and Miscellaneous Diseases (TCDMD) and from modern herbal formulas identified in the SAPHRON TCM Database using the keywords "wheezing" or "dyspnea". Compounds in the selected herbs and compounds that directly bind target proteins were acquired by searching the Herbal Ingredients' Targets Database (HITD), TCM Data Bank (TCMDB) and TCM Integrated Database (TCMID). Therapeutic targets of conventional medicine (CM) for asthma were collected by searching Therapeutic Target Database (TTD), DrugBank and PubMed as supplements. Finally, the enriched gene ontology (GO) terms of the targets were obtained using the Database for Annotation Visualization and Integrated Discovery (DAVID) and protein-protein interactions (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). The effects of two selected TCM compounds, kaempferol and ginkgolide A, on cellular resistance in human airway smooth muscle cells (ASMCs) and pulmonary resistance in a mouse model were investigated., Results: The list of 32 candidate herbs for asthma was selected from 10 CFs for the treatment of wheezing or dyspnea recorded in TCDMD and 1037 modern herbal formulas obtained from the SAPHRON TCM Database. A total of 130 compounds from the 32 selected herbs and 68 herbal compounds directly bind target proteins were acquired from HITD and TCMDB. Eighty-eight therapeutic targets of CM for asthma were collected by searching TTD and PubMed as supplements. DAVID and STRING analyses showed targets of TCM formulas are primarily related to cytochrome P450 (CYP) family, transient receptor potential (TRP) channels, matrix metalloproteinases (MMPs) and ribosomal protein. Both TCM formulas and CM act on the same types of targets or signaling pathways, such as G protein-coupled receptors (GPCRs), steroid hormone receptors (SHRs), and JAK-STAT signaling pathway. The proteins directly targeted by herbal compounds, TRPM8, TRPA1, TRPV3, CYP1B1, CYP2B6, CYP1A2, CYP3A4, CYP1A1, PPARA, PPARD, NR1I2, MMP1, MMP2, ESR1, ESR2, RPLP0, RPLP1 and RPLP2, are potential targets for asthma therapy. In vitro results showed kaempferol (1 × 10 -2  mM) and ginkgolide A (1 × 10 -5  mM) significantly increased the cell index (P < 0.05 vs. histamine, n = 3) and therefore relaxed human ASMCs. In vivo results showed kaempferol (145 μg/kg) and ginkgolide A (205 μg/kg) significantly reduced pulmonary resistance (P < 0.05 vs. methacholine, n = 6)., Conclusion: Potential target discovery for asthma treatment based on the clinical effectiveness of TCM is a feasible strategy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The traditional Chinese medicine Anluohuaxianwan (ALHXW) has been used to treat liver fibrosis induced by chronic hepatitis B virus (HBV) infection. However, the anti-fibrosis mechanisms of ALHXW remain to be investigated. This study used a rat model of carbon tetrachloride (CCl(4))-induced liver fibrosis to explore the potential antifibrogenic mechanisms of ALHXW. Methods: Twenty-seven male Wistar rats were randomly assigned to control group, model group, and treatment group ( n = 9 per group). Rats in the model and treatment group were injected intraperitoneally with 40% CCl(4)(2 ml/kg), and rats in the control group were administered saline twice a week for 6 weeks. Starting at week 4 following model construction, rats in the treatment group received daily gavages with ALHXW solution (concentration 0.15 g/ml) daily, while rats in the control and model groups were given saline for a total of 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured from blood samples collected at the end of weeks 3, 6 and 9. Histopathological examination of liver tissue was performed to evaluate liver fibrosis at week 9. At the same time, the mRNA expression of TGF-β1 and Smads in liver tissues was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR), and TGF-β1 protein level in the liver was measured by Western blot. Inter-group comparison was performed using analysis of variance (ANOVA) when the continuous data were normally distributed and satisfied the homogeneity of variance; otherwise, nonparametric tests were used. Categorical data were compared between groups using nonparametric tests. Results: ALHXW markedly alleviated liver injury in the treatment group after 3 weeks of therapy as indicated by a significantly reduced level of ALT compared with the model group [(162.98 ± 73.14)U/L vs (322.52 ± 131.76)U/L, P = 0.047], and a 39.8% reduction in AST level compared with the model group[ (537.56 ± 306.06)U/L vs (892.98 ± 358.19)U/L, P = 0.053]. Moreover, at the end of the 6-week therapy, histopathological diagnosis showed that liver fibrosis was significantly reduced in the ALHXW-treated group compared with that in the model group ( P = 0.002). The relative expression of TGF-β1 mRNA and protein in the liver were significantly lower in ALHXW-treated rats than that in model rats (1.34 ± 0.31 vs 1.78 ± 0.45, P = 0.025; 0.39 ± 0.02 vs 0.57 ± 0.04, P = 0.003). Conclusion: ALHXW treatment can reverse CCl(4)-induced liver fibrosis in rats. Its mechanisms of anti-fibrosis may occur through the inhibition of TGF-β1 synthesis and TGF-β1/Smads signaling pathway, which in turn suppress the activation of hepatic stellate cells and thereby reverses fibrosis.

This article recorded the analysis and comparison between the medicinal nature theory of traditional Chinese medicine(TCM) and ethnomedicine(EM). The vocabulary of "medicinal nature" was suggested to indicate the properties of ethnomedicine. Based on the influence of TCM medicinal nature theory on EM in China, the application of medicinal nature theory in EM was divided into 3 classes, and the standardizing principles for EM medicinal nature were proposed. It was suggested that medicinal quality, flavor, tendency, tropism, degree and efficiency can be used for the classification standard for EM medicinal nature., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Objective: To observe the effects of navel-warming therapy on clinical efficacy in patients with yang-deficiency tympanites based on regular treatment of western medication., Methods: One hundred and twenty cases of yang-deficiency tympanites were randomly divided into a navel-warming therapy group and a western medication group, sixty cases in each one. The regular treatment of western medicine was applied in the western medication group, including oral administration of antiviral drug and diuretics as well as intravenous drip of hepatic protector. Based on western medicine treatment, the navel-warming therapy was applied in the navel-warming group. A medical cake was laid on Shenque (CV 8), and then a medical cylinder was placed above the medical cake and ignited. The treatment was given once daily. One month was considered as a treatment session in both groups and totally one session was required. The TCM symptom score, B-ultrasound ascites and temporary use of diuretics before and after treatment were observed in both groups; also the efficacy was evaluated., Results: The total effective rate was 81.7% (49/60) in the navel-warming therapy group, which was superior to 56.7% (34/60) in the western medication group (P < 0.05). After the treatment, the TCM symptom score and ascites were improved in both groups (all P < 0.05), which was more significant in the navel-warming therapy group (all P < 0.05). The temporary use of diuretics was statistically different between the two groups (P < 0.05), indicating the navel-warming therapy group could obviously reduce or stop the use of diuretics., Conclusion: Based on regular treatment of western medication, the navel-warming therapy could significantly improve therapeutic efficacy, effectively relieve clinical symptoms and ease ascites.

Background: Prenatal environmental enrichment (EE) has been proven to positively affect but prenatal stress negatively influence the physiological and psychological processes in animals, whose trans-generational genetic mechanism remains unclearly defined. We aimed to investigate and find out key genes underlying the positive-negative effects derived from prenatal interventions., Materials and Methods: Pregnant rats were randomized into EE group (EEG), earthquake simulation group (ESG), herbal group (HG) received herbal supplements in feed after earthquake simulation, and control group (CG)., Results: Light Box Defecation Test (LBDT) showed EEG offspring presented less fecal pellets than CG offspring, ESG's more than CG's, and HG's less than ESG (p's<0.05). Open-field Test (OFT) score of EEG was higher than CG offspring, of ESG's was lower than CG's, and HG's higher than ESG's. Irf7 and Ninj were screened, which were up-regulated in EEG, down-regulated in ESG (FC<0.5), and were neutralized in HG. Prenatal EE could positively promote the nervous system development, prenatal earthquake simulation could retard the nervous system development and Chinese herbal remedy (JKSQW) which could correct the retardation., Conclusion: The negative-positive prenatal effect could contribute to altered gene expression of Irf7 and Ninj2 which also could play a key role in the improving function of JKSQW for the kidneys.

Objective: To observe the clinical efficacy of bushen huoxue recipe (BHR) combined estrogen and progesterone in treating premature ovarian failure (POF), and to explore an effective treatment program of POF by integrative medicine., Methods: Totally 265 POF patients were randomly assigned to 3 groups, i.e., Group I (86 cases, treated by BHR),Group II (88 cases,treated by conjugated estrogens and medroxyprogesterone acetate), and Group III (91 cases,treated by BHR +conjugated estrogens and medroxyprogesterone acetate). The therapeutic course for each group was 6 months. The main symptoms (including menstrual cycle, hectic fever, night sweat, vaginal dryness, and low libido), laboratory indices [including follicle stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), and inhibin B (INH-B)], B-ultrasound indicators (including endometrial thickness, ovarian volume, and antral follicle count), and adverse reactions were observed in the three groups at the end of treatment and 6 months after treatment., Results: Compared with before treatment, the main symptoms, laboratory indices, and B-ultrasound indicators were statistically improved in the three groups at the end of treatment and 6 months after treatment (P <0.05, P <0.01). Better effects were obtained in Group III in improving symptoms of the menstrual cycle, vaginal dryness, and low libido, lowering levels of FSH and LH, elevating levels of E2and INH-B, and ameliorating the endometrial thickness, the ovarian volume, and the antral follicle count (P <0.05, P <0.01). No obvious adverse reaction occurred in the three groups., Conclusion: BHR combined estrogen and progesterone showed better clinical efficacy than use of BHR or estrogen/progesterone alone, indicating it was an effective treatment program for POF.

Objective: To investigate the chemical components of Gardenia jasminoides., Methods: Various column chromatography were used in the isolation and purification, and physiochemical constant determination and spectral analysis were adopted to idenitify the chemical structures., Results: Ten compounds were isolated and identified as jasminoside A(1), epijasminoside A(2), 6-O-methylscandoside methyl ester (3), 6-O-methyldeacetylasperulosidic acid methyl ester (4), gardenoside (5), phenylmethol (6), 4-hydroxy-phenylmethol-O-beta-D-glucopyranosyl- (1-->6) -beta-D-glucopyranoside (7), 3,4-dihydroxy-phenylmethol-O-beta-D-glucopyranosyl-(1-6)-beta-D-glucopyranoside (8), 3-hydroxy4-methoxy-phenylmethol-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (9), 3-hydroxy-4-methoxyphenylmethol-O-beta-D-glucopyranoside (10)., Conclusion: Compounds 6 -10 are isolated from this plant for the first time.

Objective: To investigate the chemical components of Gardenia jasminoides., Methods: Various column chromatography were used in the isolation and purification. Physiochemical constant determination and spectral analysis were adopted to determine the chemical structures., Results: Ten compounds were isolated and elucidated as syringic acid (1), syringaldehyde (2), vanillic acid (3), 3-hydroxy-vanillic acid (4), 3, 4, 5-trimethoxy-phenol (5), 4-hydroxy-3,5-dimethoxy-phenol (6), 4-methoxy-benzaldehyde (7), 7-hydroxy-5-methoxy-chromone (8), crocin-1 (9), crocin-2 (10)., Conclusion: Compounds 2, 4 - 8 are first isolated from this plant.

Objective: To determinate geniposide and croein-1 in Fructus Gardeniae from different breeds., Methods: RP-HPLC method was adopted. The chromatographic separation was performed on an Eclipse XDB-C18 column (250 mm x 4.6 mm, 5 microm, Agilent). The mobile phase was a mixture of acetonitrile-0.1% phosphoric acid aqueous solution in gradient elution. The wavelength of 238 nm and 440 nm was selected to determinate geniposide and crocins simultaneously., Result: The contents of geniposide and croein-1 in different breeds of Fructus Gardeniae are different., Conclusion: This method is simple and repeatable, and could be used for the quality control of Fructus Gardeniae.

Objective: To investigate the protective effect and mechanism of Yimucao (Herba leonuri) injection against experimental cerebral ischemia., Methods: Mouse models of cerebral ischemia induced by bilateral carotid artery occlusion or potassium cyanide and rat models of middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injury were established to evaluate the protective effect of Yimucao injection by measuring the changes in cerebral malondialdehyde (MDA) content and the activities of superoxide dismutase (SOD) and lactate dehydrogenase (LDH) after the injections., Results: Yimucao injection significantly lowered the cerebral index of mice with cerebral ischemia, prolonged the survival time of mice poisoned with potassium cyanide, resulting also in significantly decreased MDA content and increased activities of SOD and LDH in the brain tissue of rats after a 10-min cerebral ischemia followed by 30 min of reperfusion., Conclusion: Yimucao injection provides protective effect against experimental cerebral ischemia.

Objective: To investigate the effect of Qianlie Huichun capsule on the microstructure and ultranstructure of prostate glandular tissue in the model rat., Method: Hynertophy of prostate model rat was established by injecting testosterone to gelding male rats. After having been fed with Qianlie Huichun capsule for 30 days, the rats were killed and prostate tissues were resected for pathomorphological studies with microscope and electromicroscope, and the diameter of glandular lumer and the height of glandular epithelial cells were measured under the microspcope for different groups of rats., Result: In the model groups, the glandular epithelial cells mutiplycated notably, showing stratified and pseudostratified cells that made the glandular lumer cramped. Under the electromicroscope, the glandular epithelial cells became high columnor and the rough endoreticulum extremely expanded. But in treatment groups, the change of the diameter of the glandular lumer and the height of the glandular epithelial cells were less remarkable than those in model groups. So the differerence between the model group and the treatment groups was remarkable (P < 0.01)., Conclusion: Qianlie Huichun capsule can depress the glandular epithelialceu multiplication of prostate gland in model rats.

Objective: To investigate the effect of Qianlie Huichun capsular on Fas expression and cell apoptosis of prostate gland tissue in the model rat., Method: Hypertrophy of prostate model rat was established by injecting testosterone to gelding male rats. After being treated with Qianlie Huichun ig 30 days, the rats were killed and prostate glands were resected for examination. The Fas expression was examined by immunobistochemical SABC. The cell apoptosis and the peak of cell apoptosis in the prostate gland of the rats were examined by flow cytometry. Compared with model group, the weight of prostage gland tissue in groups treated with Qianlie Huichun capsular was light (P < 0.01)., Result: Compared with model group, the Fas expression in all treatment groups increase(P < 0.05, P < 0.01). Compared with normal and model groups, cell apoptosis in all treatment groups increase at different level(P < 0.01)., Conclusion: The Qianlie Huchun capsular increases the Fas expression and cell apoptosis of model rats, and shows a definite treatment effect on the hypertrophy of prostate by promoting the apoptosis of prostate cell.

The article studied 61 patients with idiopathic thrombocytopenic purpura, they were classified and treated with Chinese herbal medicine Zhinu (ZN) -I, -II, in comparison with 30 cases of patients treated with prednisone. The results showed that the effect of prednisone was more effective than ZN- I, -II in four weeks (P < 0.05). On the contrary, follow up for 12 months, the effect of ZN-I, -II were more effective than prednisone (P < 0.05) and the possibility of recurrence was lower (P < 0.01). In addition, blood platelet counts of the patients treated with ZN-I, -II increased slower, but lasting for longer term. The conclusion indicated that the ZN-I, -II were safe and effective. There was no obvious side effects.

Our study reveals that the earliest historical records of Sheng Mai Powder are found in "Yixue qiyuan" ("Origins of Medicine"), a medical book written by Zhang Yuansu and published in the beginning of 1186, 45 years earlier than the latest edition of "Neiwai shangbian huolun" ("Treaties on the identification of Internal Diseases and External Damages"), written by Li Gao in 1231. The study also suggests that the assertion of Sheng Mai Powder to be inaugurated by Sun Simiao is groundless.

The effects of water soluble extract of Liriope spicata on acute hemodynamics were studied in anesthetized cats. The results showed that LV dp/dt max was increased by 87%, whereas t-dp/dt max was shortened by 28% after administration of WSEL (1.75 g/kg, iv). At the same time CO, CI, SI, and SVWI were increased by 146, 151, 153, and 194%, respectively. HR was declined slightly. SVR was reduced by about 48%. WSEL (0.7 g/kg, iv) induced an increase of 38% in LV dp/dt max, 44% in CO, 50% in SI and a decrease of 20% in t-dp/dt max and 20% in SVR. Preliminary results indicated that WSEL increased ventricular contractile force and might increase cardiac pump function.