The current difference between male and female rabbit ventricular myocytes was investigated for elucidating the mechanism of longer QT interval and higher incidence of drug-associated torsade de pointes in female rabbits than in male rabbits. Whole cell patch clamp technique was used to record APD, Ito, IK,tail, IK1 and ICa,L of myocytes from left ventricular apex. There was no difference in the membrane capacitance between male and female rabbit myocytes. APD90 was longer in female rabbits (560.4+/-26.5 ms, n=15) than in male ones (489.0+/-20.7 ms, n = 14), P<0. 05. In female rabbit myocytes, IKtail, Ito, IK1 and ICa,L were 0.71+/-0.05 pA/pF (n=17), 8.28+/-1.03 pA/pF (n=18), 24.5+/-3.6 pA/pF (n=12) and 9.0+/-2.3 pA/pF (n=15) respectively. In male rabbit myocytes, they were 0.84+/-0.07 pA/pF (n=18), 8.60+/-1.20 pA/pF (n=18), 25.9+/-4.5 pA/pF (n=14) and 9.3+2.6 pA/pF (n=16) respectively. IK,tail in female rabbits was significantly lower than that of male rabbits (P<0.05), but there was no difference in Ito,IK1 and ICa.L between male rabbits and female rabbits (P>0.05). The lower IK.tail of female rabbit myocytes may contribute to the longer repolarization and the higher incidence of drug-associated torsade de pointes.
Action Potentials/physiology ; Heart Ventricles/*physiology ; Myocytes, Cardiac/*physiology ; Patch-Clamp Techniques ; Potassium Channels/physiology ; Sex Characteristics ; Torsades de Pointes/chemically induced

In order to confirm the hypothesis that during acute hypoxia, the antiarrhythmic peptide (AAP10) could improve conductance by changing the phosphorylation state of connexin43 (Cx43), isolated perfused rat hearts were randomly divided into three groups: control, hypoxia and AAP10 (n=9 in each group). The change in Cx43 phosphorylation was tested by Western-blot; the distribution of Cx43 was observed by confocal immunofluorescence microscopy. Western-blot analysis revealed that the expression of total Cx43 protein was significantly decreased during acute hypoxia, while nonphosphorylated Cx43 (NP-Cx43) was unchanged. AAP10 could increase the expression of total Cx43 protein, but had no effects on the NP-Cx43 protein. Immunofluorescence study showed that during acute hypoxia, both total Cx43 and NP-Cx43 proteins were greatly decreased, while AAP10 only increased the expression of total Cx43 protein, but had no effect of the NP-Cx43 protein expression. These findings suggested that the decrease of intercellular communication may be associated with the reduction of phosphorylated Cx43 (p-Cx43) and translocation of NP-Cx43 from the surface of gap junction into intracellular pools during acute hypoxia. AAP10 can improve intercellular communication by enhancing phosphorylation of Cx43.

AIM: To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), and to investigate the changes of action potential duration (APD),transient outward potassium current (I to ), delayed rectifier potassium current (I K) and inward rectifier potassium current (I K1 ) of left ventricular myocytes in noninfarcted zone of HMI. METHODS: 12 rabbits were randomly assigned in two groups: HMI group (thoracotomy and ligation of the circumflex coronary); sham-operated group (thoracotomy but no conorary ligation). 3 months after operation, whole cell patch clamp technique was used to record APD, I to , I K and I K1 of ventricular myocytes in non-infarcted zone. RESULTS: Membrane capacitance was larger in HMI group than that in sham-operated group. Action potential duration was lengthened significantly in HMI group and early after depolarization (EAD) appeared in HMI group. The densities of I to , I K,tail and I K1 were reduced significantly in HMI group (P

AIM: To investigate the mechanism of gend er difference in sotalol-induced torsade de pointes (TdP) in rabbits in vitro. METHODS: 40 rabbits of both sexes were divided into two groups: low concentration (1?10 -5 mol/L d-sotalol) group and high concentration (1?10 -4 mol/L d-sotalol) group. With the monophasic action potential (MAP ) recording technique, MAP of epicardium, midmyocardium and endocardium were sim ultaneously recorded by specially designed plunge-needle electrodes across the l eft ventricular free wall of rabbit hearts purfused by Langendorff method. TdP w as induced by bradycardia, d-sotalol and low-K+, Mg 2+ tyrode solution. RESULTS: d-sotalol prolonged the duration of 90% repolarizat ion (MAPD 90) of epicardium, midmyocardium and endocardium in a concentration-d ependent manner and the effect on midmyocardium was the most obvious. In low con centration group, MAPD 90 of midmyocardium of male rabbit heart increased f rom (222?11) ms to (230?10) ms and that of female rabbit heart increased from (263?12) ms to (281?12) ms. In high concentration group, MAPD 90 of midmy ocardium of male rabbit heart increased from (217?10) ms to (296?18) ms and th at of female rabbit heart increased from (258?10) ms to (368?19) ms. There was no difference in TDR between male and female rabbit hearts before perfusion wit h d-sotalol. D-sotalol prolonged TDR in a concentration-dependent manner. In low concentration group, TDR of male and female rabbit hearts was (20.0?5.1) ms and (28.0?5.6) ms. In high concentration group, TDR of male and female rabbit hearts was (38.0?4.8) ms and (55.0?7.7) ms, respectively. There was EAD i n 6 female hearts while no EAD develop ed in male heart and no TdP developed in low concentration group. In high concen tration group, 10 female, 9 male hearts developed EAD, 9 female and 3 male he arts developed TdP. CONCLUSION: The greater TDR induced by d-sotalol in female may b e responsible for the higher incidence of TdP of female rabbit heart.

To elucidate the mechanism of arrhythmia in healed myocardial infarction (HMI), the changes of action potential duration (APD), transient outward potassium current (Ito), delayed rectifier potassium current (IK) and inward rectifier potassium current (IK1) of left ventricular myocytes in non-infarcted zone of HMI were investigated. Rabbits were randomly assigned into two groups: HMI group, in which animals were subjected to thoracotomy and ligation of the circumflex coronary and sham-operated group, in which rabbits underwent thoracotomy but no conorary ligation. 3 months after the operation, the whole myocyte patch clamp technique was used to record APD, Ito, IK, and IK1 of ventricular myocytes in non-infarcted zone. Our results showed that the membrane capacitance was larger in HMI group than in sham-operated group. Action potential duration was significantly lengthened in HMI group and early afterdepolarization (EAD) appeared in HMI group. The densities of Ito, I(K, tail), and IK1 were reduced significantly in HMI group, from 6.72 +/- 0.42 pA/pF, 1.54 +/- 0.13 pA/pF and 25.6 +/- 2.6 pA/pF in sham-operated group to 4.03 +/- 0.33 pA/pF, 1.14 +/- 0.11 pA/pF and 17.6 +/- 2.3 pA/pF, respectively. It is concluded that the reduced densities of Ito, I(K, tail) and IK1 in ventricular myocytes of non-infarcted zone in HMI were responsible for the prolongation of APD and the presentation of EAD which played important roles in the development of malignant arrhythmia in HMI.
Action Potentials ; Arrhythmia/*etiology ; Heart Ventricles/metabolism ; Myocardial Infarction/complications ; Myocardial Infarction/metabolism ; Myocardial Infarction/*pathology ; Myocytes, Cardiac/*cytology ; Patch-Clamp Techniques ; Potassium Channels/*metabolism

Objective: To explore the false-negative possibility in genetic test of congenital long QT syndrome (LQTS) by next-generation sequencing (NGS). Methods: A total of 28 genomic DNA samples were collected from 4 laboratories including 2 commercial medical laboratories using HiSeq2000 platform as Lab1,n=6 and Lab2,n=8; 1 commercial research service laboratory using Ion-torrent platform as Lab3,n=8 and 1 academic laboratory using HiSeq2000 platform as Lab 4,n=6. Sequencing coverage in the exons of protein-coding region in 3 main LQTS pathogenic genes as KCNQ1, KCNH2, SCN5A and possible pathogenic variants were quantitatively analyzed. Results: In Lab1, Lab 2 and Lab 4 with HiSeq2000 platform, above 98% protein coding regions in 3 pathogenic genes were covered with>10-fold reads and 90%-95% were covered with>30-fold reads. In 2 commercial medical laboratories, 3.63% and 9.84% protein coding regions of KCNQ1 gene in 14 samples were covered with<10-fold reads and with<30-fold reads; lower than 10-fold covering region was focused in the 1st exon including about 2% known or likely pathogenic variants. In 2 commercial medical laboratories, 2.64% and 15.76% protein coding regions of KCNH2 gene in 14 samples were covered with<10-fold reads and with<30-fold reads; low covering region was located in multiple exons. For the data from Lab 1, as high as 28.56% protein coding regions of KCNH2 gene were covered with<30-fold reads including 113 (19.79%) known or likely pathogenic variants. SCN5A gene had the best coverage of protein coding region, with no<10-fold reads in all 4 Labs and no<30-fold reads in 2 commercial medical laboratories. Conclusion: Currently, NGS has low coverage region in both KCNQ1 and KCNH2 genes, pathogenic variants could be missed and false-negative possibility should be highly alert.

Presented in this paper were 3 cases of a special kind of polymorphic ventricular tachycardia (VT). The clinical manifestation was recurrent syncope without organic heart disease. The electrocardiogram (ECG) was characterized by normal QT intervals with short-coupled variant of torsade de pointes. The efficacy of treatment with class Ⅰ,Ⅱ,Ⅲ antiarrhythmic drugs was not apparent but verapamil had an excellent therapeutic effect for it. This kind of VT had a high incidence of sudden death, so it was very important for physicians to identify and treat it promptly with long-term verapamil. The mechanism of short-coupled variant of torsade de pointes was unclear. It probably had some relationship with triggered activity or imbalance of autonomic nervous system.

Objective:To investigate the association between age and cardiac tamponade after radiofrequency ablation of atrial fibrillation(RAAF).Methods:Clinical data of patients undergone de novo AF ablation procedures at Beijing Anzhen Hospital from January 2013 to December 2016 were retrospectively collected.Patients were divided into an elderly group(age ≥60 years)and a non-elderly group(age <60 years). Logistic regression analyses were used to evaluate the association between old age and the risk of cardiac tamponade complicating RAAF.Results:A total of 5 313 patients were involved in this study, including 41 patients(0.77%)with cardiac tamponade.The proportion of cardiac tamponade was higher in the elderly group than in the non-elderly group(1.1% or 32/2 950 vs.0.4% or 9/2 363, χ2=8.489, P=0.004). One patient with cardiac tamponade in the elderly group required immediate surgical repair whereas none in the non-elderly group did.No patient died in hospital.Multivariate Logistic regression analysis showed that the risk of cardiac tamponade increased in the elderly group, compared with the non-elderly group( OR=2.570, 95% CI: 1.190-5.570, P=0.017). Stratified analysis revealed that among females and patients with oral anticoagulants, left atrium dimension < 40 mm or procedure duration≥ 120 min in the elderly group carried a higher risk of cardiac tamponade than those in the non-elderly group( OR=1.011, 2.914, 3.922 and 3.244, P<0.05). Conclusions:Old age(age ≥60 years)is an independent risk factor for cardiac tamponade complicating RAAF.

Presented in this paper were 3 cases of a special kind of polymorphic ventricular tachycardia (VT). The clinical manifestation was recurrent syncope without organic heart disease. The electrocardiogram (ECG) was characterized by normal QT intervals with short-coupled variant of torsade de pointes. The efficacy of treatment with class Ⅰ,Ⅱ,Ⅲ antiarrhythmic drugs was not apparent but verapamil had an excellent therapeutic effect for it. This kind of VT had a high incidence of sudden death, so it was very important for physicians to identify and treat it promptly with long-term verapamil. The mechanism of short-coupled variant of torsade de pointes was unclear. It probably had some relationship with triggered activity or imbalance of autonomic nervous system.

The aim of this study was to determine if the potassium aspartate and magnesium (PAM) prevent reperfusion-induced ventricular arrhythmias (RIVA) in ischemia-reperfusion (IR) rabbit heart. Thirty rabbits were randomly divided into control, ischemia and PAM groups. Arterially-perfused rabbit left ventricular preparations were made, and transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process of all experiments. In control group rabbit ventricular wedge preparations were continuously perfused with Tyrode's solution, and in ischemia group and PAM groups the perfusion of Tyrode's solution was stopped for 30 min. Then the ischemia group was reperfused with Tyrode's solution and the PAM group with Tyrode's solution containing 2.42 mg/L PAM, respectively. ECG, QT interval, transmural repolarization dispersion (TDR) and action potentials from epicardium and endocardium were simultaneously recorded, and the RIVA of the wedge preparation was observed. Compared with control group, TDR and incidence of RIVA were significantly increased in ischemia group (P<0.05). The incidence of RIVA in control, ischemia and PAM group was 0/10, 9/10 and 1/10, respectively. Compared with ischemia group, TDR and incidence of RIVA were significantly reduced in PAM group (P<0.05). Potassium aspartate and magnesium significantly reduce TDR and prevent ventricular arrhythmia in ischemic rabbit heart.
Arrhythmias, Cardiac/etiology ; Arrhythmias, Cardiac/*prevention & control ; Myocardial Ischemia/*complications ; Myocardial Ischemia/physiopathology ; Myocardial Reperfusion Injury/*complications ; Potassium Magnesium Aspartate/*therapeutic use ; Random Allocation