OBJECTIVE: To observe the immediate effect and safety of Shexiang Tongxin dropping pills (, STDP) on patients with coronary slow flow (CSF), and furthermore, to explore new evidence for the use of Chinese medicine in treating ischemic chest pain. METHODS: Coronary angiography (CAG) with corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC) was applied (collected at 30 frames/s). The treatment group included 22 CSF patients, while the control group included 22 individuals with normal coronary flow. CSF patients were given 4 STDP through sublingual administration, and CAG was performed 5 min after the medication. The immediate blood flow frame count, blood pressure, and heart rate of patients before and after the use of STDP were compared. The liver and kidney functions of patients were examined before and after treatments. RESULTS: There was a significant difference in CTFC between groups (P<0.05). The average CTFC values of the vessels with slow blood flow in CSF patients were, respectively, 49.98 ± 10.01 and 40.42 ± 11.33 before and after the treatment with STDP, a 19.13% improvement. The CTFC values (frame/s) measured before and after treatment at the left anterior descending coronary artery, left circumflex artery, and right coronary artery were, respectively, 48.00 ± 13.32 and 41.80 ± 15.38, 59.00 ± 4.69 and 50.00 ± 9.04, and 51.90 ± 8.40 and 40.09 ± 10.46, giving 12.92%, 15.25%, and 22.76% improvements, respectively. The CTFC values of vessels with slow flow before treatment were significantly decreased after treatment (P<0.05). There were no apparent changes in the heart rate, blood pressure, or liver or kidney function of CSF patients after treatment with STDP (all P>0.05). CONCLUSIONS The immediate effect of STDP in treating CSF patients was apparent. This medication could significantly improve coronary flow without affecting blood pressure or heart rate. Our findings support the potential of Chinese medicine to treat ischemic chest pain.
Blood Pressure ; drug effects ; Coronary Circulation ; drug effects ; physiology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; Humans ; Kidney ; drug effects ; physiopathology ; Liver ; drug effects ; physiopathology ; Male ; Middle Aged ; No-Reflow Phenomenon ; drug therapy ; physiopathology

Background: Valproic acid (VPA) exposure during pregnancy has been proven to contribute to congenital heart disease (CHD). Our previous findings implied that disruption of planar cell polarity (PCP) signaling pathway in cardiomyocytes might be a factor for the cardiac teratogenesis of VPA. In addition, the teratogenic ability of VPA is positively correlated to its histone deacetylase (HDAC) inhibition activity. This study aimed to investigate the effect of the VPA on cardiac morphogenesis, HDAC1/2/3, and PCP key genes (Vangl2/Scrib/Rac1), subsequently screening out the specific HDACs regulating PCP pathway. Methods: VPA was administered to pregnant C57BL mice at 700 mg/kg intraperitoneally on embryonic day 10.5. Dams were sacrificed on E15.5, and death/absorption rates of embryos were evaluated. Embryonic hearts were observed by hematoxylin-eosin staining to identify cardiac abnormalities. H9C2 cells (undifferentiated rat cardiomyoblasts) were transfected with Hdac1/2/3 specific small interfering RNA (siRNA). Based on the results of siRNA transfection, cells were transfected with Hdac3 expression plasmid and subsequently mock-treated or treated with 8.0 mmol/L VPA. Hdac1/2/3 as well as Vangl2/Scrib/Rac1 mRNA and protein levels were determined by real-time quantitative polymerase chain reaction and Western blotting, respectively. Total HDAC activity was detected by colorimetric assay. Results: VPA could induce CHD (P < 0.001) and inhibit mRNA or protein expression of Hdac1/2/3 as well as Vangl2/Scrib in fetal hearts, in association with total Hdac activity repression (all P < 0.05). In vitro, Hdac3 inhibition could significantly decrease Vangl2/Scrib expression (P < 0.01), while knockdown of Hdac1/2 had no influence (P > 0.05); VPA exposure dramatically decreased the expression of Vanlg2/Scrib together with Hdac activity (P < 0.01), while overexpression of Hdac3 could rescue the VPA-induced inhibition (P > 0.05). Conclusion VPA could inhibit Hdac1/2/3, Vangl2/Scrib, or total Hdac activity both in vitro and in vivo and Hdac3 might participate in the process of VPA-induced cardiac developmental anomalies.
Animals ; Cell Polarity ; Enzyme Inhibitors ; adverse effects ; Female ; Fetal Heart ; embryology ; Heart Defects, Congenital ; chemically induced ; physiopathology ; Histone Deacetylase Inhibitors ; Histone Deacetylases ; drug effects ; physiology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins ; Pregnancy ; Rats ; Transfection ; Valproic Acid ; adverse effects

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

PURPOSE: The aim of this study was to clarify the relationship between the autonomic nervous system and attention deficit hyperactivity disorder (ADHD) rating scales and to evaluate the usefulness of heart rate variability (HRV) as a psychophysiological biomarker for ADHD. MATERIALS AND METHODS: Subjects were recruited from outpatients in the Department of Child and Adolescent Psychiatry at the Korea University Medical Center from August 2007 to December 2010. Subjects received methylphenidate. Time- and frequency-domain analyses of HRV, the Korean ADHD rating scale (K-ARS), and computerized ADHD diagnostic system were evaluated before treatment. After a 12-week period of medication administration, we repeated the HRV measurements and K-ARS rating. RESULTS: Eighty-six subjects were initially enrolled and 37 participants completed the 12-week treatment and HRV measurements subsequent to the treatment. Significant correlations were found between the K-ARS inattention score and some HRV parameters. All of the HRV parameters, except the standard deviations of the normal-to-normal interval, very low frequency, and low frequency to high frequency, showed a significant positive correlation between baseline and endpoint measures in completers. High frequency (HF) and the square root of the mean squared differences of successive normal-to-normal intervals (RMSSD), which are related to parasympathetic vagal tone, showed significant decreases from baseline to endpoint. CONCLUSION: The HRV test was shown to be reproducible. The decrease in HF and RMSSD suggests that parasympathetic dominance in ADHD can be altered by methylphenidate treatment. It also shows the possibility that HRV parameters can be used as psychophysiological markers in the treatment of ADHD.
Adolescent ; Attention/drug effects/*physiology ; Attention Deficit Disorder with Hyperactivity/diagnosis/*drug therapy ; Autonomic Nervous System/physiopathology ; Biomarkers ; Central Nervous System Stimulants/pharmacology/*therapeutic use ; Child ; Female ; Heart Rate/*drug effects/physiology ; Humans ; Male ; Methylphenidate/pharmacology/*therapeutic use ; Prospective Studies ; Republic of Korea ; Treatment Outcome

OBJECTIVETo observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance.

METHODSA radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay.

RESULTS(1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05).

CONCLUSIONGuizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.

Animals ; Autonomic Nervous System ; drug effects ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; innervation ; physiopathology ; Heart Rate ; drug effects ; physiology ; Male ; Monitoring, Physiologic ; methods ; Rats, Wistar ; Telemetry ; methods ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; metabolism ; Vagus Nerve ; drug effects ; physiopathology

To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials ; drug effects ; Adrenergic alpha-Antagonists ; administration & dosage ; pharmacology ; Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Animals ; Anti-Arrhythmia Agents ; administration & dosage ; pharmacology ; Arrhythmias, Cardiac ; blood ; chemically induced ; etiology ; pathology ; physiopathology ; Calcium Chloride ; Creatine Kinase ; blood ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; Heart Ventricles ; cytology ; Lactate Dehydrogenases ; blood ; Male ; Myocardial Reperfusion Injury ; complications ; Myocytes, Cardiac ; drug effects ; physiology ; Ouabain ; Papillary Muscles ; cytology ; Phenoxypropanolamines ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the acute effects of aldosterone (ALD) on mesenteric resistance vessels in normal or heart failure (HF) rats and its mechanism.

METHODSHF model was adopted by in vivo ligation of left anterior descending coronary artery in SD rats; segments of third-order branches of mesenteric artery were isolated and dissected into about 2 mm rings for isometric force recording.

RESULTSPretreated with ALD for 10 min,phenylephrine (PE)-induced contraction of normal mesenteric artery decreased first and then increased compared to control group along with the increase of the concentration of PE while decreased in HF rats. This effect was attenuated by ALD receptor-special antagonist eplerenone partially. ALD increased Ach-induced endothelial-dependent vascular relaxation significantly compared to control group both in normal and HF rats. Pretreated with ALD and dexamethasone (DEX) for 10 min, the effects of ALD on PE-induced contraction were weakened in mesenteric artery both of normal and HF rats. And this reaction of DEX to ALD-treated mesenteric in normal rats was attenuated by RU486 partially.

CONCLUSIONALD has biphasic effect in PE-induced response on mesenteric artery of normal rats, while reduces the sensitivity of mesenteric artery to PE in HF rats. DEX attenuates the biphasic effect of ALD on artery of normal rat partially but has no significant effect on that of HF rats.

Aldosterone ; pharmacology ; Animals ; Heart Failure ; physiopathology ; Male ; Mesenteric Arteries ; drug effects ; physiology ; Phenylephrine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction ; drug effects

PURPOSE: Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enough to induce conventional liver damage. MATERIALS AND METHODS: Male rats were orally administered a single dose of acetaminophen at 1,000 mg/kg-body weight, and subsequently examined for conventional toxicological parameters and for gene expression alterations to both the heart and liver 24 hours after administration. RESULTS: Following treatment, serum biochemical parameters including aspartate aminotransferase and alanine aminotransferase were elevated. Histopathological alterations of necrosis were observed in the liver, but not in the heart. However, alterations in gene expression were observed in both the liver and heart 24 hours after dosing. Transcriptional profiling revealed that acetaminophen changed the expression of genes implicated in oxidative stress, inflammatory processes, and apoptosis in the heart as well as in the liver. The numbers of up-regulated and down-regulated genes in the heart were 271 and 81, respectively, based on a two-fold criterion. CONCLUSION: The induced expression of genes implicated in oxidative stress and inflammatory processes in the myocardium reflects molecular levels of injury caused by acetaminophen (APAP), which could not be identified by conventional histopathology.
Acetaminophen/*toxicity ; Administration, Oral ; Analgesics, Non-Narcotic/*toxicity ; Animals ; Drug-Induced Liver Injury/pathology/*physiopathology ; Gene Expression Profiling ; Heart/*physiology ; Liver/pathology/physiology ; Male ; Myocardium/pathology ; Rats ; Transcriptome/*drug effects

OBJECTIVETo explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule () and Kangxin Capsule () targeting on qi deficiency and blood stasis pattern in Chinese medicine (CM) in the treatment of angina pectoris.

METHODSThe data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1:1 ratio to Tongxinluo Capsule group (119 cases) and Kangxin Capsule group (120 cases). Angina effectiveness and electrocardiogram (ECG) improvement were selected as the therapeutic outcomes.

RESULTSAfter a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively (P <0.05). Serum low-density lipoprotein (LDL) level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate [Symbol: see text]80 beats/min.

CONCLUSIONLDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.

Adult ; Aged ; Angina Pectoris ; blood ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Heart Rate ; drug effects ; physiology ; Humans ; Lipoproteins, LDL ; blood ; Male ; Middle Aged ; Patient Dropouts ; Platelet Count ; Treatment Outcome

OBJECTIVETo investigate the effect of hydrogen sulfide (H2S) on mitochondrial function in acute myocardial ischemia in rats.

METHODSAcute myocardial ischemia models were established by ligating the left anterior descending coronary artery (LADC) of rats. Fourty-eight male SD rats were randomly divided into 6 groups (n = 8): sham operation group, ischemia group, ischemia + sodium hydrosulfide (NaHS) low, middle and high dose groups and ischemia + DL-proparglycine(PPG) group. The ultrastructures of myocardial mitochondria were observed with electron microscope. The content of H2S in plasma and the activity of cystathionine-gamma-lyase (CSE) in myocardial tissue of rats were respectively detected. The swelling and activity of myocardial mitochondria were determined. The activities of ATPase, GSH-Px, SOD and the content of malondial-dehyde (MDA) in myocardial mitochondria of rats were also measured.

RESULTSCompared with those of the sham operation group, the content of H2S in plasma, the activity of CSE in myocardial tissue and the activity of myocardium mitochondria were significantly decreased. The activities of ATPase, SOD, GSH-Px in myocardial mitochondria were significantly decreased, The content of malondial dehyde(MDA) in myocardial mitochondria and the swelling of mitochondria were distinctly increased in the ischemia group (P < 0.01). Compared with those of the ischemia group, the content of H2S in plasma and the activity of CSE in myocardial tissue were increased, and the activities of mitochondria, ATPase, SOD, and GSH-Px in myocardial mitochondria were significantly increased in ischemia + NaHS low, middle and high-dose groups; the swelling of mitochondria and the content of MDA in myocardial mitochondria were significantly decreased in ischemia + NaHS middle and high-dose groups (P < 0.05 or P < 0.01). The administration of PPG could partially reduce the myocardial protection of hydrogen sulfide (P < 0.05 or P < 0.01).

CONCLUSIONIt could be concluded that the administration of hydrogen sulfide could enhance the activities of mitochondrial ATPase, SOD, GSH-Px, decrease the level of mitochondrial lipid peroxidation, and play a protective effect against acute myocardial ischemia.

Adenosine Triphosphatases ; metabolism ; Animals ; Glutathione Peroxidase ; metabolism ; Hydrogen Sulfide ; pharmacology ; Lipid Peroxidation ; drug effects ; Male ; Mitochondria, Heart ; drug effects ; metabolism ; physiology ; Myocardial Ischemia ; physiopathology ; prevention & control ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism