C.-Q. Xu’s research while affiliated with Harbin Medical University and other places

The expanded skin specimens of dogs and their controls at different stages after grafting were studied. The stress-strain, stress-relaxation viseoelastic characteristics and tensile strength were measured. The results show that, during the initial stage after grafting, the biomechanical properties of expanded specimens deviate from those of their controls significantly. But the biomechanical properties of expanded specimens and their controls begin to close gradually in a longer recovering time. And when the recovering time reaches 24 weeks or longer, the experimental specimens exhibit the same mechanical characteristics as their controls. It is shown that viseoelasticity of expansive skin varies with time after grafting.

This study investigated the changes in biorheological characteristics of skin after expansion. Expanders were implanted into the back of eight adult dogs, and after an eight-week expansion the expanded and the non-expanded control skins were transferred to an adjacent site. The expanded specimens and their controls were obtained at 3, 6, 12 and 24 weeks after transfer, and their biorheological characteristics and histological changes were studied. The characteristics of the stress-relaxation, the stress-strain relationship and tensile strength of the expanded and control specimens were measured. The tests demonstrated that during the initial stage after transfer, the biorheological properties of experimental specimens differed significantly from those of their controls. However, the differences between expanded and control specimens began to lessen gradually with increasing recovery time. When the recovery time reached 24 weeks or longer, the experimental skin exhibited the same mechanical properties as the control skin. Histological examination of expanded specimens showed thickened epidermis and thinned dermis. But there were no significant histological differences between expanded skins and their controls after 24 weeks.

To study the effects of berberine on inward rectifier potassium current (IK1) and outward delayed rectifier potassium current (IK) of guinea pig ventricular myocytes, and on human ether-a-go-go related gene (HERG) channel expressed in Xenopus oocytes. Whole cell patch-clamp and geneclamp techniques were used to record ionic currents. Berberine prolonged action potential duration (APD) and inhibited IK1 and IK in a concentration-dependent manner. Berberine 100 micromol/L increased APD90 from (450 +\- 48) ms to (888 +\- 90) ms (n = 6, P < 0.01), and inhibited IK1 by 65 % +\- 7 % (n = 6, P < 0.01). Berberine 50 micromol/L inhibited IK by 57 % +\- 6 %, IKtail by 53 % +\- 6 % (n = 6, P < 0.01). Berberine produced a voltage-dependent block on IK that increased with stronger depolarization, and once all channels were activated, there was no further block at positive potentials. Berberine blocked the HERG channels potently with an IC50 value of approximately 75 micromol/L. This block was voltage-dependent, suggesting that it probably bind to either open or inactivated HERG channels. Berberine prolonged APD and possessed blocking effect on IK1, IK, and HERG channel expressed in Xenopus oocytes. The antiarrhythmic mechanism of berberine is related to its inhibitory effects on IK1, IK, and HERG channel.

The effect of RP62719 on the inward rectifier K(+) current (I(K1)),transient outward K(+) current (I(to)) and delayed outward K(+) current (I(K)) in isolated cardiac myocytes was determined using the whole cell patch clamp technique in guinea pig and dog. RP62719 decreased I(K1) with an inhibitory concentration 50 (IC(50) ) of 5.0+/-1.0 micromol/L at -100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP62719 inhibited Ito by 84+/-4.4% with an IC(50) of 1.2+/-0.51 micromol/L at +40 mV. In guinea pig ventricular cells, RP62719 decreased I(K): I(Kstep) by 50.0+/-8.3%%and I(Ktail) by 56.0+/-4.9% at +40 mV, respectively. RP62719 inhibited I(Kstep) with an IC(50) of 4.2+/-0.8 micromol/L and I(Ktail) with an IC(50) of 3.3+/-0.75 micromol/L. Thus it is suggested that the ionic mechanism of antiarrhymic effect by RP62719 may be due to its inhibition of I(K1),I(to) and I(K).

To determine effects of RP58866 on inward rectifier K+ current (IKl), transient outward K+ current (Ito) and delayed outward rectifier K+ current (IK) in isolated cardiac myocytes. In isolated ventricular myocytes of guinea pig and dog, the effect of RP58866 on IKl, Ito, and IK were observed by the whole cell voltage-clamp technique. RP58866 decreased IKl in a concentration-dependent manner, with an IC50 of (3.4 +/- 0.8) micromol.L-1 (n = 6) at -100 mV in guinea pig ventricular cells. In dog ventricular myocytes, RP58866 inhibited Ito with IC50 of (2.3 +/- 0.5) micromol.L-1 at +40 mV. In guinea pig ventricular cells, RP58866 at 100 micromol.L-1 decreased IK: IKstep by (58 +/- 13)% at +40 mV, and IKtail by (86 +/- 17)%, respectively. RP58866 inhibited IKstep with an IC50 of (7.5 +/- 0.8) micromol.L-1, and IKtail with an IC50 of (3.5 +/- 0.9) micromol.L-1. The envelope of tail analysis suggested that both IKr and IKs were inhibited. RP58866 inhibits IKl, Ito, and IK in cardiac myocytes with a similar potency, and is not a specific IKl inhibitor.

AIM: To study the antiarrhythmic effect of artemisinin (As) and its antiarrhythmic mechanism. METHODS: Arrhythmia induced by coronary artery ligation and CaCl2, chloroform in rats and mice was used as the experimental models for the study of antiarrhythmic effect of As, in the same time, the effect of As on inward rectifier potassium current was investigated by using patch-clamp whole cell recording techniques. RESULTS: As showed marked effects on counteracting arrhythmias induced by coronary artery ligation, and markedly prolonged the onset time of arrhythmia and reduced the ventricular fibrillation induced by CaCl2 and chloroform in mice and rats. In patch- clamp experiment, inward rectifier potassium current was specifically inhibited by As in a concentration dependent fashion. CONCLUSION: As is an effective antiarrhythmic drug, the mechanism of As on antiarrhythmic action might be due to its inhibiting inward rectifier potassium current effect.

The effect of artemisinin (Art) on one of major types of cloned inward rectifier potassium channel (K(ir2.1) channel) expressed in Xenopus oocytes was examined using a two electrode voltage clamp. Art reduced the functional expression of K(ir2.1) channels in Xenopus oocytes in a concentraction-dependent manner when the oocytes were perfused by Art after cRNA injection. Art blocked the K(ir2.1) channels also in voltage-dependent fashion. When command voltage was -140, -130 and -120 mV, Art in 5 and 50 μmol · L-1 reduced the inward current through K(ir2.1) channel by 14.2%, 34.5%; 12.0%, 24.6%; 4.3%, 19.1%, respectively. When command voltage was -50, -40 and -30 mV, Art in 5 and 50 μmol · L-1 increased the outward current through K(ir2.1) channel by 22.2%, 72.2%; 28.0%, 80.0%; 24.1%, 69.0%, respectively. The blockade of Art on the K(ir2.1) channels was recovered after washing using normal perfusing solution. The results suggest that the antiarrhythmic action of Art is caused by its blocking effect on K(ir2.1) channels.

AIM: To observe the effects of safflower yellow pigment (SYP) on action potential and calcium current in single guinea-pig ventricular myocyte. METHODS: The patch-clamp whole cell recording technique was used. RESULT: SYP (3.3 μg · L-1) prolonged the APD from (359.33 ± 27.18) ms to (413.33 ± 61.88) ms (P < 0.05, n = 6), while it increased the peak current of L-type calcium current from (-1 021 ± 74) pA to (-1 436 ± 212) pA (P < 0.05, n = 7). CONCLUSION: SYP can be used for the treatment of heart failure and rapid arrhythmias due to its electrophysiological action.

The effects of artemisinin on the potassium ionic currents of guinea pig ventricular cells and dog Purkinje fibres were studied using the whole cell voltage clamp technique. Artemisinin significantly decreased inward rectifier K+ current (I(Kl)) with an IC50 of (7.2 ± 0.8) μmol·L-1 at -100 mV in guinea pig ventricular cells. The blocking effect on I(Kl) was concentration-dependent, but not frequency-dependent. In dog Purkinje fibres, artemisinin significantly inhibited the transient outward K+ current (I(to)) (decreased by 84% at 100 μmol·L-1) in a concentration-dependent manner, with an IC50 of (4.7 ± 0.3) μmol·L-1. In guinea pig ventricular cells, artemisinin at 50 μmol·L-1 decreased the delayed outward rectifier K+ current (I(K)); time-dependent outward potassium current (I(Kstep)) by (38 ± 10)% at +40 mV. The envelope of tail analysis suggested that both the rapid component (I(Kr)) and the slow component (I(Ks)) of I(k) be inhibited. These results suggest that artemisinin inhibit I(Kl), I(to) and I(K) in cardiac myocytes with similar potency, which may be related to the antiarrhythmic action of artemisinin.

The present study was designed to determine the effects of artemisinin on the inward rectifier K+ current (I(K1)), transient outward K+ current (I(to)) and the delayed outward rectifier K+ current (I(K)) in isolated cardiac myocytes using the whole cell voltage clamp technique. Artemisinin significantly decreased I(K1) in a concentration-dependent manner, with an IC50 of 7.2 ± 0.8 μM at -100 mV in guinea pig ventricular cells. In dog ventricular myocytes, artemisinin significantly inhibited the I(to) (decreased by 84% at 100 μM) with an IC50 of 4.2 ± 0.3 μM. In guinea pig ventricular cells, artemisinin at 50 μM decreased I(K): I(Kstep) (time- dependent outward potassium current) by 38% ± 9.8% at +40 mV. The envelope of tail analysis suggested that both the rapid component of the delayed rectifier K+ current (I(Kτ)) and the slow component of delayed rectifier K+ current (I(Ks)) were inhibited. Our results indicate that artemisinin inhibits I(K1), I(to) and I(K) in cardiac myocytes with similar potency. The mechanism of antiarrhythmic action by artemisinin may be related to the inhibition of I(K1), I(to), I(Kr) and I(Ks).