Ion mechanism of isoproterenol on delayed afterdepolarization and triggered activity in the infarcted ventricle

Objectives This study aimed at investigating the cellular mechanism of isoproterenol （ISO） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model.Methods Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 wk （healed myocardial infarction, HMI）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. ISO was added to cellular surface by perfusion way. Action potentials and ion currents were recorded with whole-cell patch clamp. Results The results showed that treatment with ISO induced more DADs and TA events in HMI myocytes. Iti and IC,_L of myocytes treated with ISO were increased significantly compared with HMI cells, which contributed to DADs-related triggered arrhythmia. Conclusions The results suggested that more arrhythmia events of DADs and TA developed in myocytes with ISO treatment. The underlying mechanism was associated with the augment of I6 and calcium influxing

Effects of nerve growth factor on delayed afterdepolarization and triggered activity in the infarcted ventricle of rabbit model

The noninfarcted myocardium underwent significant electrophysiological remodelling as part of the healed myocardial infarction remodelling. This study aimed at investigating the effects of nervous growth factor （NGF） on delayed afterdepolarizations （DADs） and triggered activity （TA） of the noninfarcted myocardium in the myocardial infarcted rabbit model. Rabbits with the left anterior descending coronary artery occlusion were prepared and recovered for 8 weeks （HMI group, n=9）. Other rabbits with myocardial infarction were infused NGF to the left stellate ganglion （HMI＋NGF group, 400 U/day for 8 weeks, n=8）. Myocytes were isolated from regions of the noninfarcted left ventricular free wall. Action potentials and ion currents were recorded with whole-cell patch clamp. The results showed that more DADs and TA events of HMI＋NGF myocytes than that of HMI and Ctrl group. Iti and ICa-L of NGF＋HMI myocytes were increased significantly compared with HMI and Ctrl cells, which contributed to DADs-related triggered arrhythmia. Comparing with HM1 and Ctrl myocytes, significant prolongations of APD50 and APD90 in HMI＋NGF myocytes were found. The results indicated the electrophysiological change of HMI myocytes with NGF infusion. It suggested that more events of DADs and TA in HMI myocytes with NGF treatment. The underlying mechanism may be involved in the increase of Iti and ICa-L.

An Active Triggered Surge Protective Gap

A triggered surge protective device is designed and its discharge characteristics axe studied. The experimental results show that the triggered surge protective device has excellent surge protective characteristics. When the gap distance is 5 mm, p. d is 90 Pa.mm and without an active energy trigger circuit, the DC breakdown voltage of the triggered surge protective device is 2.32 kV and the pulse breakdown voltage is 5.75 kV. Therefore, the pulse voltage ratio, which is defined as the specific value of pulse breakdown voltage and DC breakdown voltage, is 2.48. With a semiconductor ZnO flashover trigger device and an active energy coupling trigger circuit, the pulse breakdown voltage can be reduced to 3.32 kV, the pulse voltage ratio is 1.43 and the response time is less than 100 ns. These results are helpful in laying a theoretical foundation for further studies on triggered surge protective devices.

Age-related increase of early afterdepolarization in calsequestrin-2 knock-in mouse cardiomycyte

Objective To characterize early afterdepolarizations （EADs） caused triggered activity （TA） among calsequestrin-2 （CASQ2） knock-in （CASQ2 KI） mice and its relationship with aging. Methods Electrophysiological properties of ventricular myocytes from 3- month （mo, young）, 9-mo （adult-l） and 12-too （adult-2） in wild-type （WT） and CASQ2 KI mice were investigated with patch-clamp technique. Results The incidences of EADs and TA in CASQ2 KI cardiomyocytes increased with increasing age. In contrast, WT mice cardiomyocytes showed no significant change in matched-age groups. Compared with that in 3-mo CASQ2 KI mice, the 50% repolarization of action potential （APD50） showed prolongation in both 9-mo and 12-mo ones （9.2±0.9 ms of 9-mo and 10.3 ± 1.2 ms of 12- mo vs. 5.6± 0.3 ms of 3-mo）, while the 90 % repolarization of action potential （APD90） was similar among 3 age groups. Compared with 3-mo mice, the 9-mo and 12-mo CASQ2 KI mice showed markedly reduced transient outward potassium current （Ito） densities but increased L-type calcium current （ICa-L） densities. Conlcusion This study suggested that events of EADs and TA in CASQ2 KI mice increased with increasing age, It might be associated partly with the augment of cellular calcium concentration and the prolongation of APD50 induced by decrease of Ito and increase of ICa-L in adult CASQ2 KI mice

L-type calcium current in right ventricular outflow tract myocytes of rabbit heart

The mechanism of idiopathic ventricular tachycardia originating from the right ventricular outflow tract （RVOT） is not clear. Many clinical reports have suggested a mechanism of triggered activity. However, there are few studies investigating this be- cause of the technical difficulties associated with examining this theory. The L-type calcium current （/Ca-L）, an important in- ward current of the action potential （AP）, plays an important role in arrhythmogenesis. The aim of this study was to explore differences in the APs of right ventricular （RV） and RVOT cardiomyocytes, and differences in electrophysiological character- istics of the ICa-L in these myocytes. Rabbit RVOT and RV myocytes were isolated and their AP and Ic,-L were investigated us- ing the patch-clamp technique. RVOT cardiomyocytes had a wider range of AP duration （APD） than RV cardiomyocytes, with some markedly prolonged APDs and markedly shortened APDs. The markedly shortened APDs in RVOT myocytes were abolished by treatment with 4-AP, an inhibitor of the transient outward potassium current, but the markedly prolonged APDs remained, with some myocytes with a long AP plateau not repolarizing to resting potential. In addition, early afterdepolariza- tion （EAD） and second plateau responses were seen in RVOT myocytes but not in RV myocytes. RVOT myocytes had a high- er current density for/Ca-L than RV myocytes （RVOT （13.16±0.87） pA pF-1, RV （8.59±1.97） pA pF-1; P〈0.05）. The ICa-L and the prolonged APD were reduced, and the EAD and second plateau response disappeared, after treatment with nifedipine （10 μmol L^-1）, which blocks the Ica-L. In conclusion, there was a wider range of APDs in RVOT myocytes than in RV myocytes, which is one of the basic factors involved in arrhythmogenesis. The higher current density for ICa-L is one of the factors causing prolongation of the APD in RVOT myocytes. The combination of EAD with prolonged APD may be one of the mechanisms of RVOT-VT generation.