To discuss the protective effect of aralosides (AS) on I/R-induced rat myocardial injury. The adult rat ventricular myocyte ischemia model was established through perfusion with sodium lactate perfusate and reperfusion with Ca(2+) -containing Tyrode's solution simulation. The cell contraction and ion concentration synchronization determination system was applied to detect the effect of AS on single I/R cell contraction and Ca2+ transients. According to the findings, AS could increase resting sarcomere length, contraction amplitude, ± dL/dt(max), calcium transient amplitude and speed of post-reperfusion myocardial cells (P < 0.05, P < 0.01), and decrease in time for achieving 90.0% of maximum relaxation, time for achieving peak value, resting calcium ratio, contraction period [Ca2+] i, time for achieving 50.0% of maximum relaxation and attenuation rate of intracellular calcium transient (P < 0.05, P < 0.01). Therefore, it is suggested that AS improved the post-reperfusion cell contraction and injury of calcium homeostasis.
Animals ; Aralia ; chemistry ; Biological Transport ; drug effects ; Calcium ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Muscle Contraction ; drug effects ; Myocardial Ischemia ; drug therapy ; metabolism ; physiopathology ; surgery ; Myocardial Reperfusion ; Myocytes, Cardiac ; drug effects ; physiology ; Rats ; Rats, Sprague-Dawley ; Saponins ; administration & dosage

This study examined the effect of cholic acid (CA) on cultured cardiac myocytes (CMs) from neonatal rats with an attempt to explore the possible mechanism of sudden fetal death in intrahepatic cholestasis of pregnancy (ICP). Inverted microscopy was performed to detect the impact of CA on the beating rates of rat CMs. MTT method was used to study the effect of CA on the viability of CMs. CMs cultured in vitro were incubated with 10 μmol/L Ca(2+)-sensitive fluorescence indicator fluo-3/AM. The fluorescence signals of free calcium induced by CA were measured under a laser scanning confocal microscope. The results showed that CA decreased the beating rates of the CMs in a dose-dependent manner. CA could suppress the activities of CMs in a time- and dose-dependent manner. CA increased the concentration of intracellular free calcium in a dose-dependent manner. Our study suggested that CA could inhibit the activity of CMs by causing calcium overload, thereby leading to the sudden fetal death in ICP.
Animals ; Animals, Newborn ; Calcium ; metabolism ; Cells, Cultured ; Cholestasis, Intrahepatic ; complications ; metabolism ; physiopathology ; Cholic Acid ; metabolism ; pharmacology ; Death, Sudden ; etiology ; Dose-Response Relationship, Drug ; Female ; Fetal Death ; etiology ; Humans ; Microscopy, Confocal ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; drug effects ; metabolism ; physiology ; Pregnancy ; Pregnancy Complications ; metabolism ; physiopathology ; Rats, Sprague-Dawley ; Time Factors

PURPOSE: Despite the fact that desflurane prolongs the QTC interval in humans, little is known about the mechanisms that underlie these actions. We investigated the effects of desflurane on action potential (AP) duration and underlying electrophysiological mechanisms in rat ventricular myocytes. MATERIALS AND METHODS: Rat ventricular myocytes were enzymatically isolated and studied at room temperature. AP was measured using a current clamp technique. The effects of 6% (0.78 mM) and 12% (1.23 mM) desflurane on transient outward K+ current (I(to)), sustained outward current (I(sus)), inward rectifier K+ current (I(KI)), and L-type Ca2+ current were determined using a whole cell voltage clamp. RESULTS: Desflurane prolonged AP duration, while the amplitude and resting membrane potential remained unchanged. Desflurane at 0.78 mM and 1.23 mM significantly reduced the peak I(to) by 20+/-8% and 32+/-7%, respectively, at +60 mV. Desflurane (1.23 mM) shifted the steady-state inactivation curve in a hyperpolarizing direction and accelerated inactivation of the current. While desflurane (1.23 mM) had no effects on I(sus) and I(KI), it reduced the L-type Ca2+ current by 40+/-6% (p<0.05). CONCLUSION: Clinically relevant concentrations of desflurane appear to prolong AP duration by suppressing Ito in rat ventricular myocytes.
Action Potentials/*drug effects ; Anesthetics, Inhalation/*pharmacology ; Animals ; Calcium Channels, L-Type/physiology ; Heart Conduction System/drug effects/physiology ; Heart Ventricles/drug effects ; Isoflurane/*analogs & derivatives/pharmacology ; Myocardial Contraction/*drug effects/physiology ; Myocytes, Cardiac/*drug effects/physiology ; Patch-Clamp Techniques ; Potassium Channels/physiology ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe microemboli produced during spontaneous plaque rupture and ulceration and during coronary intervention will reduce coronary reserve and cause cardiac dysfunction. It is though that inflammation caused by the microinfarction induced by the microembolization may play an essential role. It is known that the activation of p38 mitogen-activated protein kinases (MAPK) in both infected and non-infected inflammation in myocardium may cause a contractile dysfunction. But the relation between the activation of p38 MAPK and microembolization is still unknown.

METHODSSprague-Dawley rats were randomly divided into three groups: Sham group, coronary microembolization (CME) group and SB203580 group (n = 10 per group). CME rats were produced by injection of 42 µm microspheres into the left ventricle with occlusion of the ascending aorta. SB203580, a p38 MAPK inhibitor, was injected into the femoral vein after the injection of microspheres to make the SB203580 group. Left ventricular ejection fraction (LVEF) was determined by echocardiography. The protein concentration of P38 MAPK in the myocardium was assessed by Western blotting. The relative expression of mRNA for tumor necrosis factor (TNF)-α was assessed by the technique of semi-quantitative polymerase chain reaction amplification.

RESULTSLVEF was depressed at three hours up to 12 hours in the CME group. Increased p38 MAPK activity and TNF-α mRNA expression were observed in the CME group. The administration of SB203580 partly inhibited p38 MAPK activity, but did not fully depress the TNF-α expression, and partly preserved cardiac contractile function.

CONCLUSIONSp38 MAPK is significantly activated by CME and the inhibition of p38 MAPK can partly depress the TNF-α expression and preserve cardiac contractile function.

Animals ; Blotting, Western ; Coronary Disease ; drug therapy ; etiology ; metabolism ; Echocardiography ; Embolism ; complications ; Imidazoles ; pharmacology ; therapeutic use ; Immunohistochemistry ; Microcirculation ; drug effects ; Myocardial Contraction ; drug effects ; physiology ; Myocardium ; metabolism ; Pyridines ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Reverse Transcriptase Polymerase Chain Reaction ; Tumor Necrosis Factor-alpha ; genetics ; p38 Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism

OBJECTIVETo investigate effects of GBE50 on the physiological characteristics and intracellular free calcium of myocardium.

METHODThe preparations of isolated atria of guinea pigs were used for recording the myocardial physiological characteristics and the technique of Fluo-3/AM was used for measuring the concentration of free calcium in myocytes.

RESULTGBE50 (10, 20, 40, 80, 160 mg x L(-1)) prominently inhibited the contractive force and decreased spontaneous beat of right atrium in concentration-dependent manner. GBE50 (10, 20, 40, 80, 160 mg x L(-1)) inhibited the contractive force of left atrium, and markedly decreased the post rest potentiation of myocardial contractility in left atrium in concentration-dependent manner. GBE50 (10, 20, 40, 80, 160 mg x L(-1)) prolonged the function refractory period of isolated guinea pig left atrium. 50 mg x L(-1) GBE50 decreased [Ca2+]i of guinea pig ventricular myocytes in normal Tyrode's solution by (46.53 +/- 8.44)% in 12 minutes.

CONCLUSIONGBE50 induces inhibitory effects of the spontaneous beat, contractility, post-rest potentiation and prolonged the function refractory period. GBE50 may decrease [Ca2+]i of guinea pig ventricular myocytes.

Animals ; Calcium ; metabolism ; Cells, Cultured ; Ginkgo biloba ; chemistry ; Guinea Pigs ; Heart ; drug effects ; physiology ; In Vitro Techniques ; Male ; Myocardial Contraction ; drug effects ; Myocardium ; metabolism ; Myocytes, Cardiac ; drug effects ; metabolism ; Plant Extracts ; pharmacology

OBJECTIVETo study the effect of Xinjining extract (, XJN) on inward rectifier potassium current (I(K1)) in ventricular myocyte (VMC) of guinea pigs and its anti-arrhythmic mechanism on ion channel level.

METHODSSingle VMC was enzymatically isolated by zymolisis, and whole-cell patch clamp recording technique was used to record the I(k1) in VMC irrigated with XJN of different concentrations (1.25, 2.50, 5.00 g/L; six samples for each). The stable current and conductance of the inward component of I(K1) as well as the outward component of peak I(K1) and conductance of it accordingly was recorded when the test voltage was set on -110 mV.

RESULTSThe suppressive rate of XJN on the inward component of I(K1) was 9.54% + or - 5.81%, 34.82% + or - 15.03%, and 59.52% + or - 25.58% with a concentration of 1.25, 2.50, and 5.00 g/L, respectively, and that for the outward component of peak I(K1) was 23.94% + or - 7.45%, 52.98% + or - 19.62%, and 71.42% + or - 23.01%, respectively (all P<0.05). Moreover, different concentrations of XJN also showed effects for reducing I(K1) conductance.

CONCLUSIONXJN has inhibitory effect on I(K1) in guinea pig's VMC, and that of the same concentration shows stronger inhibition on outward component than on inward component, which may be one of the mechanisms of its anti-arrhythmic effect.

Animals ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; pharmacology ; Electrophysiology ; Guinea Pigs ; Heart Ventricles ; drug effects ; metabolism ; Membrane Potentials ; drug effects ; Myocardial Contraction ; drug effects ; Myocytes, Cardiac ; drug effects ; metabolism ; physiology ; Potassium Channels, Inwardly Rectifying ; drug effects ; metabolism ; physiology ; Ventricular Function ; drug effects

The present study is aimed to study the effect of sarcoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) gene transfer on the contractile function of isolated cardiomyocytes of canines. The cardiomyocytes were isolated with collagenases. The isolated cardiac cells were divided into untransfected group, empty vector group and SERCA2a-transfected group. Recombinant adenovirus vector carrying enhanced green fluorescent protein gene was used for SERCA2a gene delivery. The expression of SERCA2a protein in cardiomyocytes was determined by Western blot. Contractile function of cardiomyocytes was measured with motion edge-detection system of single cell at 48 h after transfection. The results showed, compared with untransfected group, SERCA2a protein level, percentage of peak contraction amplitude under normal condition, percentages of peak contraction amplitude under Ca(2+) or isoproterenol stimulation, time-to-peak contraction (TTP) and time-to-50% relaxation (R50) in SERCA2a-transfected group all increased significantly. While all the above indices in empty vector group did not show any differences with those in untransfected group. These results suggest that the overexpression of SERCA2a by gene transfer may enhance the contraction function of canine myocardial cells.
Adenoviridae ; genetics ; metabolism ; Animals ; Dogs ; Male ; Myocardial Contraction ; drug effects ; physiology ; Myocytes, Cardiac ; metabolism ; Recombinant Proteins ; genetics ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; genetics ; metabolism ; Transfection

OBJECTIVETo study the protective effects of tetramethylpyrazine (TMPZ) on rat myocardial cells infected by Coxsackie virus B3 (CVB3) and its signal transduction mechanism.

METHODSThe cultured myocardial cells of neonatal Sprague-Dawley rats were randomly treated with CVB3, CVB3+TMPZ (100 micromol/L), TMPZ (100 micromol/L) (negative control) or DMEM (blank control). After treatment, the beating rate of myocardial cells and the LDH activity in the culture fluid were measured. Cell viability was ascertained with MTT assay. Western blot was used to study the expression of nuclear factor kappa-B (NF-kappaB) protein in myocardial cells.

RESULTSThe beating rate of myocardial cells in the untreated CVB3 infection group was significantly lower than that in the TMPZ-treated CVB3 infection group (32.0+/-3.6 bpm vs 84.3+/-3.5 bpm, P<0.01). The LDH activity and NF-kappaB expression in the TMPZ-treated CVB3 infection group was significantly reduced when compared with untreated CVB3 infection group (P<0.05, P<0.01, respectively). Cell viability 7 days after CVB3 infection in the TMPZ-treated group was higher than that in the untreated CVB3 infection group (86.7+/-2.7% vs 35.3+/-3.4%; P<0.01).

CONCLUSIONSTMPZ can provide protective effects on rat myocardial cells infected by CVB3, possibly by an inhibition of the activity of NF-kappaB in myocardial cells.

Animals ; Cytoprotection ; Enterovirus B, Human ; L-Lactate Dehydrogenase ; metabolism ; Myocardial Contraction ; drug effects ; Myocarditis ; drug therapy ; Myocytes, Cardiac ; drug effects ; virology ; NF-kappa B ; analysis ; physiology ; Pyrazines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; physiology

OBJECTIVETo study the vasodilation effects of the Total alkali Sophora alopecuroids L (TASa) on rabbit thoracic aortic rings in vitro and the possible mechanisms.

METHODRabbit aortic rings were isolated and precontracted with noradrenaline (NA) and then were divided into six groups including control group, TASa group, TASa + 1 x 10(-5) mol x L(-1) indomethacin (Indo), TASa + 1 x 10(-5) mol x L(-1) propranolol (Prop), TASa + 1 x 10(-10 mol x L(-1) N(omega)-nitro-L-arginine (L-NNA), TASa + removal of endothelium. The vasodilation effects of TASa were investigated. In addition, the thoracic aortic rings were pre-treated with TASa (40 mg x L(-1)) and then the thoracic aortic rings were treated with cumulative NA (110(-8)-110(-5) mol x L(-1)), KCl (6.3-100 mmol x L(-1)) or CaCl2 (110(-5)-110(-2) mol x L(-1)). The dose response curves of aortic rings were recorded.

RESULTTASa can relax isolated rabbit aorta and has an obvious concentration-dependent relaxation (r = 0.94, P < 0.01). The relaxant effect of TASa was no significant reducing by removal of endothelium and by treatment with L-NNA, Indo or Prop. In addition, TASa can decrease the dose response curves of aortic rings to NA, KCl or CaCl2.

CONCLUSIONThe vasodilation effects of TASa are related to not only inhibition of intracellular calcium release, but also reduction to calcium flow to the interior of the cell with blockage of calcium channels.

Alkalies ; pharmacology ; Animals ; Aorta, Thoracic ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Myocardial Contraction ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; Rabbits ; Sophora ; chemistry ; Vasodilator Agents ; chemistry ; pharmacology

AIMTo investigate the effects of endothelin-1 (ET-1) and nitric oxide (NO) on lipopolysaccharide(LPS)-induced myocardial dysfunction, and explore the related underlying mechanisms.

METHODSExperimental septic model was established by intraperitoneal injection of LPS (10 mg x kg(-1)). The study was carried out on the isolated rat hearts to determine the roles of ET-1 and NO in the effect of LPS on the cardiac contractility and on the isolated rat ventricular myocytes model to observe the [Ca2+]i homeostasis in cardiac myocytes.

RESULTS(1) The levels of serum NO2-/NO3- and plasma ET-1 were markedly increased by LPS treatment for 4 hours. (2) LPS induced the decrease in rate-pressure product (RPP), and increase in left ventricular end-diastolic pressure (LVEDP) in the isolated perfused rat hearts. Pretreatment with either aminoguanidine (AMG) (100 mg x kg(-1), i.p.) or BQ-123 (1 mg x kg(-1), i.p.) partially attenuated LPS-induced myocardial depression. When these two drugs were simultaneously given, myocardial depression elicited by LPS was almost abolished. (3) LPS significantly decreased the amplitude of caffeine induced [Ca2+]i transients compared to the control cells. The activity of SR Ca22+ -ATPase was significantly decreased in the cardiac myocytes from LPS-treated rats. Single pretreatment with either AMG or BQ-123 did not attenuate the impairment of SR Ca2+ -ATPase induced by LPS.

CONCLUSIONET-1 and NO mediate myocardial dysfunction in hearts isolated and decrease [Ca2+]i transients in cardiac myocytes from LPS-treated rats. But neither ET-1 nor NO participates in the impairment of SR Ca2+ -ATPase induced by LPS.

Animals ; Depression, Chemical ; Endothelin-1 ; physiology ; Lipopolysaccharides ; toxicity ; Male ; Myocardial Contraction ; drug effects ; physiology ; Nitric Oxide ; physiology ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; chemically induced ; physiopathology