Heart ; drug effects ; Heart Failure ; drug therapy ; Humans ; Hydrogen Bonding ; Nitrogen Oxides ; pharmacology ; therapeutic use

BACKGROUNDShen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels.

METHODSThe Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP).

RESULTSSSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change.

CONCLUSIONSThe present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

Action Potentials ; drug effects ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Guinea Pigs ; Heart ; drug effects ; physiology ; Heart Rate ; drug effects ; Heart Ventricles ; In Vitro Techniques ; Male ; Myocytes, Cardiac ; drug effects ; physiology ; Sinoatrial Node ; drug effects ; physiology ; Swine ; Swine, Miniature

Angiotensin II ; pharmacology ; Animals ; Heart Rate ; 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

Action Potentials ; drug effects ; physiology ; Animals ; Female ; Guinea Pigs ; Heart Ventricles ; drug effects ; Papillary Muscles ; drug effects ; physiology ; Progesterone ; pharmacology

OBJECTIVEOn the basis that pinacidil can produce an "all or none" repolarization in right ventricular wall of canine, to observe the effects of quinidine on the marked transmural dispersion of repolarization. Recent studies have shown that ventricular myocardium is composed of at least 3 electrophysiological distinct cell types: epicardial, endocardial, and midcardial cells. Differences in the response of the 3 cell types to pharmacologic agents and/or pathophysiological states often result in amplification of intrinsic electrical heterogeneities, thus providing a substrate as well as a trigger for the development of arrhythmias. The study was designed to observe the right ventricular transmural heterogeneity in vitro canine heart tissue preparation level.

METHODSThe strips were isolated from the anterior wall of the right ventricular of canine. The preparations perfused with oxygenated (95%O(2)/5%CO(2)) Tyrode's solution. The tissues were stimulated at basic cycle lengths of 1000 ms. Standard microelectrode techniques were used. Transmembrane action potentials were recorded from epicardial, midcardial and endocardial cells respectively from right ventricular free wall of canine on different conditions [perusing with Tyrode's solution (Control), pinacidil (2.5 micromol/L), and quinidine (5 micromol/L) in turn].

RESULTSCompared with that of endocardial cells, the action potentials of canine ventricular epicardial and midcardial cells had more obvious spike and dome morphology. Pinacidil (2.5 micromol/L) caused a loss of the dome of transmembrane action potentials and a marked abbreviation of the action potential duration (APD) in right ventricular epicardial and midcardial cells, especially in epicardial cells, but not in endocardial cells (n = 10). With pinacidil (2.5 micromol/L), in epicardial cells, phase 2 amplitude of action potentials decreased from (117.7 +/- 9.3) mV to (71.3 +/- 6.4) mV (P < 0.01), and 90% of the APD(90) decreased from (198.2 +/- 20.8) ms to (103.9 +/- 13.5) ms (P < 0.01). The transmural dispersion of action potential duration increased from (48.5 +/- 9.2) ms to (128.7 +/- 13.5) ms (P < 0.01). Quinidine (5 micromol/L) effectively prolonged the APD abbreviated by pinacidil, restored or partly restored the dome of transmembrane action potentials of epicardial and midcardial cells but not of endocardial cells (n = 10). In epicardial cells phase 2 amplitude increased from (71.3 +/- 6.4) mV to (106.6 +/- 7.7) mV (P < 0.01), and 90% of the APD(90) increased from (103.9 +/- 13.5) ms to (185.9 +/- 15.7) ms (P < 0.01). The transmural dispersion of action potential duration significantly decreased from (128.7 +/- 13.5) ms to (54.3 +/- 10.8) ms (P < 0.01). Quinidine reduced pinacidil-induced transmural dispersion of phase 2 amplitude and the APD in right ventricular wall of canine.

CONCLUSIONBy restoring the dome and the APD of the epicardial and midcardial cells action potentials, quinidine (5 micromol/L) could reduce the marked transmural dispersion of repolarization caused by pinacidil.

Action Potentials ; drug effects ; Animals ; Dogs ; Heart Ventricles ; drug effects ; physiopathology ; Pinacidil ; pharmacology ; Quinidine ; pharmacology

OBJECTIVEAlthough after pacing animal and human studies have demonstrated a rate-dependent effect of sotalol on ventricular repolarization, there is little information on the effects of sotalol on ventricular repolarization during exercise. This study attempted to show the effects of sotalol on ventricular repolarization during physiological exercise.

METHODSThirty-one healthy volunteers (18 males, 13 females) were enrolled in the study. Each performed a maximal treadmill exercise test according to the Bruce protocol after random treatment with sotalol, propranolol and placebo.

RESULTSSotalol significantly prolonged QTc (corrected QT) and JTc (corrected JT) intervals at rest compared with propranolol (QTc 324.86 ms vs 305.21 ms, P<0.001; JTc 245.04 ms vs 224.17 ms, P<0.001) and placebo (QTc 324.86 ms vs 314.06 ms, P<0.01; JTc 245.04 ms vs. 232.69 ms, P<0.001). The JTc percent reduction increased progressively with each stage of exercise and correlated positively with exercise heart rate (r=0.148, P<0.01). The JTc percent reduction correlation with exercise heart rate did not exist with either propranolol or placebo.

CONCLUSIONSThese results imply that with sotalol ventricular repolarization is progressively shortened after exercise. Thus the specific class III antiarrhythmic activity of sotalol, present as delay of ventricular repolarization, may be attenuated during exercise. Such findings may imply the need to consider other antiarrythmic therapy during periods of stress-induced tachycardia.

Adult ; Exercise ; physiology ; Exercise Test ; Female ; Heart ; drug effects ; physiopathology ; Heart Rate ; drug effects ; physiology ; Humans ; Male ; Sotalol ; pharmacology

AIMTo investigate the role of intracerebroventricular (icv) injection substance P(SP) in cardiovascular regulation and the relationship with noradrenergic system.

METHODSRabbits anesthetized with urethane were intracerebroventricularly given SP in presence or absence of phentolamine, prazosin, yohimbine. Cardiovascular responses including heart rate (HR), mean arterial blood pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximum velocity of ascending or descending in intraventricular pressure (+/- dp/dt(max)) and the maximum shortening velocity(Vpm) of myocardial contractile element were recorded, and changes of NA content in cerebrospinal fluid (CSF) were determined in rabbits with icy injection of SP.

RESULTS(1) icv SP elicited significant increased of HR, MAP, LVSP, LVEDP, + dp/dt(max), -dp/dt(max), Vpm and the levels of NA in intracisternal CSF 30 min after injection. (2) Pretreatment with phentolamine, prazosin, but not yohimbine, attenuated icv SP-induced cardiovascular responses compared with controls (P < 0.05).

CONCLUSION(1) icv SP can produce positive inotropic and chronic response in myocardium and pressor response in intact rabbits. (2) alpha1 adrenoceptors may be involved in the cardiovascular responses to icy SP. (3) Central administration of SP can increase the release of NA or inhibit reuptake of NA, which may be responsible for an important mechanism of SP-potentiated cardiovascular responses in brain.

Animals ; Blood Pressure ; drug effects ; Heart ; drug effects ; Heart Rate ; drug effects ; Lateral Ventricles ; Myocardium ; Norepinephrine ; cerebrospinal fluid ; Rabbits ; Substance P ; pharmacology

The purpose of this study was to investigate the different effects of ACh on the action potential and force contraction in guinea pig atrial and ventricular myocardium by using standard microelectrodes and force transducer. The results showed that the duration of the action potential (APD) of atrial myocardium was shortened from 208.57+/-36.05 to 101.78+/-14.41 ms (n=6, P<0.01), and the APD of the ventricular myocardium was shortened from 286.73+/-36.11 to 265.16+/-30.06 ms (n=6, P<0.01).The amplitude of the action potential (APA) of the atrial myocardium was decreased from 88.00+/-9.35 to 62.62+/-20.50 mV (n=6, P<0.01), while the APA of the ventricular myocardium did not change significantly.The force contraction of atrial myocardium was inhibited completely (n=6, P<0.01), while the force contraction of ventricular myocardium was inhibited by 37.57+/-2.58% (n=6, P<0.01). The ACh effects correlated with its concentration. The K(D) of the APD shortening effects in the atrial and ventricular myocardium were 0.275 and 0.575 micromol/L. The K(D) of the negative inotropic in the atrial and ventricular myocardium were 0.135 and 0.676 micromol/L, respectively. The corresponding data points were compared using t test between the atrial and ventricular myocardium, and the differences were significant when the ACh concentration was above 10 nmol/L. Furthermore, atropine (10 micromol/L) and CsCl (20 mmol/L) blocked the effects of 10 micromol/L ACh on the APD of ventricular myocardium, while CdCl2 (0.1 mmol/L) had no influence on these effects. In conclusion, ACh could shorten the action potential duration and inhibit the force contraction of atrial and ventricular myocardium in a concentration-dependent manner. There are differences in the effects of ACh on the atrial and ventricular myocardium. The atrial myocardium is more sensitive to ACh than the ventricular myocardium. It is probable that the muscarinic receptor and the potassium channel, but not the calcium channel, are involved in the ACh-induced shortening of the ventricular APD.
Acetylcholine ; pharmacology ; Action Potentials ; drug effects ; Animals ; Calcium Channels ; metabolism ; Guinea Pigs ; Heart Atria ; drug effects ; Heart Ventricles ; drug effects ; Microelectrodes ; Potassium Channels ; metabolism ; Receptors, Muscarinic ; metabolism

AIMTo explore the effect and mechanism of interleukin-2 (IL-2) on the rhythm of isolated rat heart and neonatal myocytes.

METHODSCultured neonatal rat cardiomyocytes and isolated perfused rat heart were used.

RESULTS(1) IL-2 (2.5-200 u/ml) reduced the spontaneous beating rate of cultured neonatal rat cardiomyocytes in a dose-dependent manner. (2) IL-2 at 50 u/ml increased both the heart rate and the number of premature ventricular excitation in the isolated heart. (3) Pretreatment with propranolol abolished the effect of 50 u/ml IL-2 on the isolated heart. (4) Heat inactivated IL-2 had no significant effect on the cultured cardiomyocytes and isolated hearts.

CONCLUSIONIL-2 inhibited the auto rhythmic of cultured cardiomyocyte directly while the positive chronotropic and arrhythmogenic effects of IL-2 in the isolated rat heart may be mediated by endogenous catecholamine.

Animals ; Animals, Newborn ; Cells, Cultured ; Heart ; drug effects ; Heart Rate ; drug effects ; In Vitro Techniques ; Interleukin-2 ; pharmacology ; Myocytes, Cardiac ; drug effects ; physiology ; Propranolol ; pharmacology ; Rats ; Rats, Sprague-Dawley