Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

This study was aimed to establish an experimental mouse model of combined transgenic inhibition of both multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and inward rectifier potassium current (Ik1), and to observe whether the specific inhibition of both CaMKII and Ik1 can bring about any effects on cardiac remodeling. Mice were divided into 4 groups: wild type (WT), CaMKII inhibited (AC3-I), Ik1 inhibited (Kir2.1-AAA) and combined inhibition of both CaMKII and Ik1 (AC3-I+Kir2.1-AAA). Mice in each group received electrocardiogram (ECG) and echocardiography examination. ECG in the condition of isoproterenol (ISO) injection was also checked. The whole cell patch clamp technique was used to measure Ik1 and the transient outward potassium current (Ito) from enzymatically isolated myocytes of left ventricle. In the condition of basal status, no significant changes of heart rate, PR interval and QRS interval were observed. No mouse showed ventricular arrhythmias in all of the 4 groups. After ISO injection, each group presented no significant ventricular arrhythmias either. The indexes measured by M-mode (motion-mode) and two-dimensional echocardiography had no significant differences among the four groups. Ik1 in AC3-I group was significantly higher than those in other three groups (P < 0.01) because of the results brought about by CaMKII inhibition. Among the latter three groups, both Kir2.1-AAA group and AC3-I+Kir2.1-AAA group had a significant reduced Ik1 compared with that of WT group, which was due to the Ik1 inhibition (P < 0.01). Ito in AC3-I group was higher than that of the other three groups (P < 0.01), but there were no significant differences in Ito among WT, Kir2.1-AAA and AC3-I+Kir2.1-AAA groups. Thus, combined transgenic myocardial CaMKII and Ik1 inhibition eliminated the up-regulation of Ik1 in CaMKII inhibited mice, and had no effects on cardiac remodeling including heart structure and function as well as arrhythmias at the basic and ISO conditions. The results of this study may provide a basis for the further investigation of combined inhibition of CaMKII and Ik1 in pathogenic cardiac remodeling.
Animals ; Arrhythmias, Cardiac ; Brugada Syndrome ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; physiology ; Cardiac Conduction System Disease ; Disease Models, Animal ; Electrocardiography ; Heart ; physiology ; Heart Conduction System ; abnormalities ; Heart Ventricles ; Isoproterenol ; Mice ; Mice, Transgenic ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; physiology ; Up-Regulation ; Ventricular Remodeling

Mutation or common intronic variants in cardiac ion channel genes have been suggested to be associated with sudden cardiac death caused by idiopathic ventricular tachyarrhythmia. This study aimed to find mutations in cardiac ion channel genes of Korean sudden cardiac arrest patients with structurally normal heart and to verify association between common genetic variation in cardiac ion channel and sudden cardiac arrest by idiopathic ventricular tachyarrhythmia in Koreans. Study participants were Korean survivors of sudden cardiac arrest caused by idiopathic ventricular tachycardia or fibrillation. All coding exons of the SCN5A, KCNQ1, and KCNH2 genes were analyzed by Sanger sequencing. Fifteen survivors of sudden cardiac arrest were included. Three male patients had mutations in SCN5A gene and none in KCNQ1 and KCNH2 genes. Intronic variant (rs2283222) in KCNQ1 gene showed significant association with sudden cardiac arrest (OR 4.05). Four male sudden cardiac arrest survivors had intronic variant (rs11720524) in SCN5A gene. None of female survivors of sudden cardiac arrest had SCN5A gene mutations despite similar frequencies of intronic variants between males and females in 55 normal controls. Common intronic variant in KCNQ1 gene is associated with sudden cardiac arrest caused by idiopathic ventricular tachyarrhythmia in Koreans.
Adolescent ; Adult ; Aged ; Arrhythmias, Cardiac/genetics ; *Death, Sudden, Cardiac ; Ether-A-Go-Go Potassium Channels/genetics ; Female ; Genetic Markers ; Genetic Predisposition to Disease ; Genetic Variation ; Heart/physiology ; Heart Conduction System/abnormalities ; Humans ; KCNQ1 Potassium Channel/*genetics ; Male ; Middle Aged ; NAV1.5 Voltage-Gated Sodium Channel/*genetics ; Republic of Korea ; Tachycardia, Ventricular/*genetics ; Ventricular Fibrillation/*genetics ; Young Adult

Electrical instability easily induces a unidirectional conduction block, resulting in ventricular tachycardia (VT) or even fibrillation (VF). Cardiac memory affects dynamic electrical characteristics through previous pacing so that it makes the memory important in arrhythmia study. This paper investigates the impact of the rapid pacing duration on cellular excitability and its mechanism. Based on the canine endocardial single cell, a one-dimensional tissue model was developed. Simulations were realized with OpenMP parallel programming method. The results showed that with repetitive pacing, the cellular excitability became low while the conduction velocity decreased. Accumulation of intracellular [Ca2+]i and [Na+]i and depletion of [K+]i led to the shift of membrane current-voltage curves, changing the membrane resistance. Excitability determined by the resistance at the large width of stimulus pulse, therefore, it suggested that [Ca2+]i and [K+]i-induced memory formed the ionic substrates for the alteration of excitability.
Action Potentials ; Animals ; Computer Simulation ; Dogs ; Electric Stimulation ; Electrocardiography ; Heart Conduction System ; physiopathology ; Myocardial Contraction ; physiology ; Myocytes, Cardiac ; physiology ; Refractory Period, Electrophysiological ; physiology ; Tachycardia, Ventricular ; etiology ; physiopathology ; Ventricular Fibrillation ; etiology ; physiopathology

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

Under conditions of Na+ channel hyperactivation with aconitine, the changes in action potential duration (APD) and the restitution characteristics have not been well defined in the context of aconitine-induced arrhythmogenesis. Optical mapping of voltage using RH237 was performed with eight extracted rabbit hearts that were perfused using the Langendorff system. The characteristics of APD restitution were assessed using the steady-state pacing protocol at baseline and 0.1 microM aconitine concentration. In addition, pseudo-ECG was analyzed at baseline, and with 0.1 and 1.0 microM of aconitine infusion respectively. Triggered activity was not shown in dose of 0.1 microM aconitine but overtly presented in 1.0 microM of aconitine. The slopes of the dynamic APD restitution curves were significantly steeper with 0.1 microM of aconitine than at baseline. With aconitine administration, the cycle length of initiation of APD alternans was significantly longer than at baseline (287.5 +/- 9.6 vs 247.5 +/- 15.0 msec, P = 0.016). The functional reentry following regional conduction block appears with the progression of APD alternans. Ventricular fibrillation is induced reproducibly at pacing cycle length showing a 2:1 conduction block. Low-dose aconitine produces arrhythmogenesis at an increasing restitution slope with APD alternans as well as regional conduction block that proceeds to functional reentry.
Aconitine/*pharmacology ; Action Potentials/*drug effects ; Animals ; Arrhythmias, Cardiac/*chemically induced/*physiopathology ; Cardiac Pacing, Artificial ; Electrocardiography ; Heart/physiopathology ; Heart Conduction System/physiology ; Myocardium/*pathology ; Rabbits ; Sodium Channels/drug effects/metabolism ; Ventricular Fibrillation/physiopathology

Ventricular fibrillation (VF) is the main cause of sudden death in cardiovascular diseases. The effects of electrophysiological heterogeneity and dynamic factors bring a lot of difficulties in understanding and revealing the mechanisms of VF. Cardiac short-term memory is one of the factors that make invalidation of restitution curve slope as the criteria for transition from ventricular tachycardia to VF. Therefore, investigation of inherent properties of short-term memory and its role in VF has great significance. In this paper we took advantage of the perturbed down-sweep protocol to measure dynamic and local S1S2 restitution curves on three widely used mathematical models to reveal their memory property. And by making abrupt change of the stimulation cycle length, we examined the attenuation process of the memory. The results showed, the rate-dependent action potendial duration (APD) is related with S1 pacing. The APD difference under different S2 cycle length is more pronounced with short S1 cycle length. Except the Luo-Rudy 1991 model, the Luo-Rudy 1994 and Noble 1991 models can at least reflect some of the short-term memory. And the memory attenuated in exponential way. Therefore, in quantitative electrophysiological study, these two models can be used in the future for investigating the characteristics of the short-term memory and its contribution to VF.
Action Potentials ; Computer Simulation ; Electrocardiography ; Heart Conduction System ; physiopathology ; Humans ; Models, Cardiovascular ; Models, Theoretical ; Myocardial Contraction ; physiology ; Ventricular Fibrillation ; physiopathology ; Ventricular Function

BACKGROUNDBoth early repolarization and altered heart rate profile are associated with sudden death. In this study, we aimed to demonstrate an association between early repolarization and heart rate profile during exercise.

METHODSA total of 84 subjects were included in the study. Comparable 44 subjects with early repolarization and 40 subjects with normal electrocardiogram underwent exercise stress testing. Resting heart rate, maximum heart rate, heart rate increment and decrement were analyzed.

RESULTSBoth groups were comparable for baseline characteristics including resting heart rate. Maximum heart rate, heart rate increment and heart rate decrement of the subjects in early repolarization group had significantly decreased maximum heart rate, heart rate increment and heart rate decrement compared to control group (all P < 0.05). The lower heart rate increment (< 106 beats/min) and heart rate decrement (< 95 beats/min) were significantly associated with the presence of early repolarization. After adjustment for age and sex, the multiple-adjusted OR of the risk of presence of early repolarization was 2.98 (95%CI 1.21-7.34) (P = 0.018) and 7.73 (95%CI 2.84-21.03) (P < 0.001) for the lower heart rate increment and heart rate decrement compared to higher levels, respectively.

CONCLUSIONSSubjects with early repolarization have altered heart rate profile during exercise compared to control subjects. This can be related to sudden death.

Adult ; Autonomic Nervous System ; physiology ; Case-Control Studies ; Electrocardiography ; Exercise ; physiology ; Exercise Test ; Female ; Heart Conduction System ; physiopathology ; Heart Rate ; Humans ; Male

UNLABELLEDForty SD rats were divided into 5 groups: control group, SP groups (5 microg/kg,10 microg/kg, 20 microg/kg) and spantide II plus SP group. An analysis of heart rate variability (HRV) was used to detect the changes of HRV parameters before and after intravenous injection of SP in order to investigate the effect of substance P on cardiac autonomic nervous function and the corresponding mechanism.

RESULTS(1) There were significant differences in most HRV parameters for the three different doses of SP. Mean heart period (MHP), absolute power of ultra-low frequency and high frequency band (APU, APH), total power (TPV) and ratio of power in ultra-low to high frequency band (RUH) increased, while mean heart rate (MHR) and chaos intensity (HCC) decreased during the 30 minutes. Each peak amplitude of HRV parameters went higher and showed up ahead of the upward doses of SP. (2) Significant change was seen in each of the parameters between spantide II plus SP group and high-dose SP group. These data idicate that, after intravenous injection of different doses of SP, both cardiac sympathetic nervous system activity and parasympathetic nervous system activity increase, and the function of cardiac autonomic nervous becomes instable and unbalanced. The effect of SP may be dose dependent, and it is possibly mediated by neurokinin-1(NK-1) receptor.

Animals ; Autonomic Nervous System ; drug effects ; physiology ; Female ; Heart Conduction System ; drug effects ; physiology ; Heart Rate ; drug effects ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Receptors, Neurokinin-1 ; physiology ; Substance P ; pharmacology