OBJECTIVE: To explore the synergic mechanism of ginsenoside Rg₁ (Rg₁) and aconitine (AC) by acting on normal neonatal rat cardiomyocytes (NRCMs) and pentobarbital sodium (PS)-induced damaged NRCMs. METHODS: The toxic, non-toxic, and effective doses of AC and the most suitable compatibility concentration of Rg₁ for both normal and damaged NRCMs exposed for 1 h were filtered out by 3- (4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, respectively. Then, normal NRCMs or impaired NRCMs were treated with chosen concentrations of AC alone or in combination with Rg₁ for 1 h, and the cellular activity, cellular ultrastructure, apoptosis, leakage of acid phosphatase (ACP) and lactate dehydrogenase (LDH), intracellular sodium ions [Na⁺], potassium ions [K⁺] and calcium ions [Ca²⁺] levels, and Nav1.5, Kv4.2, and RyR₂ genes expressions in each group were examined. RESULTS: For normal NRCMs, 3000 µ mol/L AC significantly inhibited cell viability (P<0.01), promoted cell apoptosis, and damaged cell structures (P<0.05), while other doses of AC lower than 3000 µ mol/L and the combinations of AC and Rg₁ had little toxicity on NRCMs. Compared with AC acting on NRCMs alone, the co-treatment of 3000 and 10 µ mol/L AC with 1 µ mol/L Rg₁ significantly decreased the level of intracellular Ca²⁺ (P<0.01 or P<0.05), and the co-treatment of 3000 µ mol/L AC with 1 µ mol/L Rg₁ significantly decreased the level of intracellular Ca²⁺ via regulating Nav1.5, RyR₂ expression (P<0.01). For damaged NRCMs, 1500 µ mol/L AC aggravated cell damage (P<0.01), and 0.1 and 0.001 µ mol/L AC showed moderate protective effect. Compared with AC used alone, the co-treatment of Rg₁ with AC reduced the cell damage, 0.1 µ mol/L AC with 1 µ mol/L Rg₁ significantly inhibited the level of intracellular Na⁺ (P<0.05), 1500 µ mol/L AC with 1 µ mol/L Rg₁ significantly inhibited the level of intracellular K⁺ (P<0.01) via regulating Nav1.5, Kv4.2, RyR₂ expressions in impaired NRCMs. CONCLUSION Rg₁ inhibited the cardiotoxicity and enhanced the cardiotonic effect of AC via regulating the ion channels pathway of [Na⁺], [K⁺], and [Ca²⁺].
Aconitine/pharmacology* ; Animals ; Apoptosis ; Cardiotonic Agents/pharmacology* ; Cardiotoxicity/drug therapy* ; Cell Survival ; Ginsenosides/pharmacology* ; Rats

The effect of drugs on calcium-binding to cardiac muscle membrane fragments and its turnover rate was studied. Ouabian, acetylcholine, isoproterenol and norepinephrine did not have any effect either on calcium-binding to membrane fragments or an washout ahnd release curves of previously bound calcium. Local anesthetics inhibited the calcium-binding. Tetracaine at concentrations of 1 and 10 mM inhibited the calcium-binding by 30% and 54%, respectively, while 10 mM lidocaine inhibited it by 17%. Propranolol, a well-known adrenergic beta-blocker, also inhibited calcium-binding at the external calcium concentration of 10(-3) M. This effect of propranolol may be attributed to its local anesthetic-like action, rather than to the adrenergic blocking effect.
Anesthetics, Local/pharmacology* ; Animal ; Calcium/metabolism* ; Cardiotonic Agents/pharmacology* ; Cell Membrane/metabolism ; In Vitro ; Myocardium/metabolism*

The effect of drugs on calcium-binding to cardiac muscle membrane fragments and its turnover rate was studied. Ouabian, acetylcholine, isoproterenol and norepinephrine did not have any effect either on calcium-binding to membrane fragments or an washout ahnd release curves of previously bound calcium. Local anesthetics inhibited the calcium-binding. Tetracaine at concentrations of 1 and 10 mM inhibited the calcium-binding by 30% and 54%, respectively, while 10 mM lidocaine inhibited it by 17%. Propranolol, a well-known adrenergic beta-blocker, also inhibited calcium-binding at the external calcium concentration of 10(-3) M. This effect of propranolol may be attributed to its local anesthetic-like action, rather than to the adrenergic blocking effect.
Anesthetics, Local/pharmacology* ; Animal ; Calcium/metabolism* ; Cardiotonic Agents/pharmacology* ; Cell Membrane/metabolism ; In Vitro ; Myocardium/metabolism*

This study is aimed to investigate the intervention effect and possible mechanism of ophiopogonin D( OPD) in protecting cardiomyocytes against ophiopogonin D'( OPD')-induced injury,and provide reference for further research on toxicity difference of saponins from ophiopogonins. CCK-8 assay was used to evaluate the effect of OPD and OPD' on cell viability. The effect of OPD on OPD'-induced cell apoptosis was measured by flow cytometry. Morphologies of endoplasmic reticulum were observed by endoplasmic reticulum fluorescent probe. PERK,ATF-4,Bip and CHOP mRNA levels were detected by Real-time quantitative polymerase chain reaction( PCR) analysis. ATF-4,phosphorylated PERK and e IF2α protein levels were detected by Western blot assay. RESULTS:: showed that treatment with OPD'( 6 μmol·L-1) significantly increased the rate of apoptosis; expressions of endoplasmic reticulum stress related genes were increased. The morphology of the endoplasmic reticulum was changed. In addition,different concentrations of OPD could partially reverse the myocardial cell injury caused by OPD'. The experimental results showed that OPD'-induced myocardial toxicity may be associated with the endoplasmic reticulum stress,and OPD may modulate the expression of CYP2 J3 to relieve the endoplasmic reticulum stress caused by OPD'.
Apoptosis ; Cardiotonic Agents ; pharmacology ; Cells, Cultured ; Endoplasmic Reticulum Stress ; drug effects ; Humans ; Myocytes, Cardiac ; drug effects ; Saponins ; pharmacology ; Spirostans ; pharmacology

AIMTo study the regular pattern and mechanism of positive inotropic effect after washout of ACh (rebound of myocardial contractile force) in isolated rabbit hearts.

METHODSThe changes of myocardial contractile force after perfusion and washout of ACh were observed in isolated Langendorff perfused rabbit hearts.

RESULTSMaximum rebound rate induced by ACh of 10(-8)-10(-3) mol/L were 2.20% +/- 1.70%, 6.71% +/- 3.40%, 9.18% +/- 3.54%, 14.16% +/- 3.27%, 4.37% +/- 5.86% and 1.03% +/- 6.86%, respectively. Compared with the ACh of 10(-5) mol/L in control group, adrenaline enhanced rebound of myocardial contractile force, maximum rebound rate in adrenaline group was 29.25% +/- 5.83% (P < 0.05), propranolol reduced rebound, and maximum rebound rate in propranolol group was 5.15% +/- 4.45% (P < 0.05), we had not detected rebound of myocardial contractile force in 800 s after addition ACh in verapamil group.

CONCLUSIONIn isolated rabbit heart, positive inotropic effect after washout of ACh has relevance to the activities of calcium current channel and beta-adrenergic receptor. Perhaps there are some different aspects in the mechanism of positive inotropic effect between perfusion of high concentration and after washout of ACh.

Acetylcholine ; pharmacology ; Animals ; Cardiotonic Agents ; pharmacology ; Heart ; drug effects ; In Vitro Techniques ; Myocardial Contraction ; drug effects ; physiology ; Rabbits

Ginseng, the root of Panax ginseng C. A. Mayer, has long been used clinically in China to treat various diseases. Multiple effects of ginseng, such as antitumor, antiinflammatory, antiallergic, antioxidative, antidiabetic and antihypertensive have been confirmed by modern medicine. Recently, the clinical utilization of ginseng to treat heart diseases has increased dramatically. The roles of ginseng in protecting heart are foci for research in modern medical science and have been partially demonstrated, and the mechanisms of protection against coronary artery disease, cardiac hypertrophy, heart failure, cardiac energy metabolism, cardiac contractility, and arrhythmia are being uncovered progressively. However, more studies are needed to elucidate the complex mechanisms by which ginseng protects heart. All such studies will provide evidence of ginseng's clinical application, international promotion, and new drug development.
Animals ; Cardiotonic Agents ; chemistry ; pharmacology ; Energy Metabolism ; drug effects ; Heart ; drug effects ; physiopathology ; Humans ; Myocardial Contraction ; drug effects ; Panax ; chemistry

OBJECTIVETo investigate the cardioprotective effects of morphine on ischemic reperfused rat heart in vitro and its mechanism.

METHODSThe isolated rat heart was perfused in a Langendorff apparatus. Infarct myocardium was determined by TTC. Coronary flow (CF), heart rate (HR), left ventricular pressure (LVP), the first derivative of ventricular pressure (LVP/dtmax) and infarct size after ischemia and reperfusion in rat heart given 0.3 micro mol/L morphine were observed. The effects of naloxone and glibenclamide on the cardioprotection of morphine were also measured.

RESULTSAfter ischemia and reperfusion, CF, HR, LVP and LVP/dtmax of isolated rat hearts decreased significantly (P < 0.01). After morphine preconditioning, HR, LVP and LVP/dtmax increased (P < 0.01) and infarct size was reduced significantly (P < 0.01), while no significant change in CF (P > 0.05). The cardioprotective effects of morphine were abolished by naloxone or glibenclamide completely.

CONCLUSIONSMorphine can reduce ischemia-reperfusion injuries in isolated rat heart. The cardioprotective effects of morphine are mediated by a local opioid receptor-K(ATP) channel linked mechanism in rat hearts.

Animals ; Cardiotonic Agents ; pharmacology ; Glyburide ; pharmacology ; Heart ; drug effects ; In Vitro Techniques ; Ischemic Preconditioning, Myocardial ; Male ; Morphine ; pharmacology ; Myocardial Reperfusion Injury ; prevention & control ; Naloxone ; pharmacology ; Rats ; Rats, Wistar

With the fast development of medicinal animals as new drugs, research on Periplaneta americana become hot recently. Several drugs which mainly consisted of P. americana were approved for clinical applications. The chemical constituents and pharmacological bioactivities of this insect were summarized herein, which provides informativon for further researches on this medicinal animal.
Amino Acids ; isolation & purification ; pharmacology ; Animals ; Anti-Bacterial Agents ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cardiotonic Agents ; pharmacology ; Cycloparaffins ; isolation & purification ; pharmacology ; Materia Medica ; isolation & purification ; pharmacology ; Molecular Structure ; Neuropeptides ; isolation & purification ; pharmacology ; Periplaneta ; chemistry

Survival rates after cardiac arrest have not changed substantially over the past 5 decades. Postcardiac arrest (CA) syndrome (PCAS) is the primary reason for the high mortality rate after successful restoration of spontaneous circulation (ROSC). Intravenous administration of Shenfu Injection (, SFI) may attenuate post-CA myocardial dysfunction and cerebral injury, inhibit systemic ischemia/reperfusion responses, and treat underlying diseases. In this article, we reviewed the therapeutic effects of SFI in PCAS. SFI might be useful in the treatment of PCAS, incorporating the multi-link and multi-target advantages of Chinese medicine into PCAS management. Further experimental and clinical research to verify the therapeutic effects of SFI in PCAS is required.
Cardiotonic Agents ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Heart Arrest ; drug therapy ; physiopathology ; Humans ; Injections ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Syndrome

To investigate the effects of metallothionein (MT) on isolated rat heart, 16 Wistar rats were randomly divided into 2 groups. In control group (group C), distilled water was injected intraperitoneally and 24 h later isolated hearts were perfused with Langendorff and stored at 4 degrees C for 3 h with histidine-tryptophan-ketoglutarate (HTK) solutions, and then isolated hearts were perfused for 2 h by Langendorff. In experimental group (group E), 3.6% ZnSO(4) was injected intraperitoneally, 24 h later isolated hearts were perfused by Langendorff and stored at 4 degrees C for 3 h with HTK solutions, and then the isolated hearts were perfused for 2 h with Langendorff. MT content, the recovery of hemodynamics, myocardial water content (MWC), lactate dehydrogenase (LDH) and creatine kinase (CK) leakage, adenosine triphosphate (ATP) and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, myocardial cell Ca(2+) content, Ca(2+)-ATPase activity of mitochondria ([Ca(2+)-ATPase](m)) and its Ca(2+) content ([Ca(2+)](m)), synthesizing ATP activity of mitochondria ([ATP](m)), and the ultrastructure of cells were examined. There were a significant increase in group E in hemodynamic recovery, ATP content, SOD activity, [Ca(2+)-ATPase](m) activity, [ATP](m) activity, and substantial reduction in MWC, LDH and CK leakage, MDA content, myocardial cell Ca(2+) content, [Ca(2+)](m) content, and the ultrastructural injury were obviously milder than that of group C. This study demonstrated that MT has protective effects on isolated rat heart.
Cardiotonic Agents/*pharmacology ; Creatine Kinase/*metabolism ; L-Lactate Dehydrogenase/metabolism ; Metallothionein/biosynthesis ; Metallothionein/*pharmacology ; Myocardium/*metabolism ; Myocardium/ultrastructure ; Random Allocation ; Rats, Wistar ; Superoxide Dismutase/metabolism ; Zinc Sulfate/pharmacology