Stimulation and propagation of activation in conduction tissue: Implications for left bundle branch area pacing.

BACKGROUND: Characterizing wavefront generation and impulse conduction in left bundle (LB) has implications for left bundle branch area pacing (LBBAP). OBJECTIVES: The purpose of this study was to describe the pacing characteristics of LB and to study the role of pacing pulse width (PW) in overcoming left bundle branch block. METHODS: Twenty fresh ovine heart slabs containing well-developed and easily identifiable tissues of the conduction system were used for the study. LB stimulation, activation, and propagation were studied under baseline conditions, simulated conduction slowing, conduction block, and fascicular block. RESULTS: The maximum radius of the LB early activation increased up to 13.4 ± 2.4 mm from the pacing stimulus, and the time from stimulus to evoked potential shortened when pacing PW was increased from 0.13 to 2 ms at baseline. Conduction slowing and block induced by cooling could be resolved by increasing pacing PW from 0.25 to 1.5 ms over a distance of 10 ± 1.5 mm from the pacing stimulus. The LB strength-duration (SD) curve was shifted to the left of the myocardial SD curve. CONCLUSION: Increasing PW resolved conduction slowing and block and bypassed the experimental model of fascicular block in LB. Precise positioning of the LB lead in left ventricular subendocardium is not mandatory in LBBAP, as the SD curve of LB was shifted to the left of the myocardium SD curve and could be captured from a distance by optimizing PW.

Dantrolene improves survival after ventricular fibrillation by mitigating impaired calcium handling in animal models.

BACKGROUND: Resistant ventricular fibrillation, refibrillation. and diminished myocardial contractility are important factors leading to poor survival after cardiac arrest. We hypothesized that dantrolene improves survival after ventricular fibrillation (VF) by rectifying the calcium dysregulation caused by VF. METHODS AND RESULTS: VF was induced in 26 Yorkshire pigs for 4 minutes. Cardiopulmonary resuscitation was then commenced for 3 minutes, and dantrolene or isotonic saline was infused at the onset of cardiopulmonary resuscitation. Animals were defibrillated and observed for 30 minutes. To study the effect of VF on calcium handling and its modulation by dantrolene, hearts from 14 New Zealand rabbits were Langendorff-perfused. The inducibility of VF after dantrolene administration was documented. Optical mapping was performed to evaluate diastolic spontaneous calcium elevations as a measure of cytosolic calcium leak. The sustained return of spontaneous circulation (systolic blood pressure ≥60 mm Hg) was achieved in 85% of the dantrolene group in comparison with 39% of controls (P=0.02). return of spontaneous circulation was achieved earlier in dantrolene-treated pigs after successful defibrillation (21 ± 6 s versus 181 ± 57 s in controls, P=0.005). The median number of refibrillation episodes was lower in the dantrolene group (0 versus 1, P=0.04). In isolated rabbit hearts, the successful induction of VF was achieved in 83% of attempts in controls versus 41% in dantrolene-treated hearts (P=0.007). VF caused diastolic calcium leaks in the form of spontaneous calcium elevations. Administration of 20 µmol/L dantrolene significantly decreased spontaneous calcium elevation amplitude versus controls. (0.024 ± 0.013 versus 0.12 ± 0.02 arbitrary unit [200-ms cycle length], P=0.001). CONCLUSIONS: Dantrolene infusion during cardiopulmonary resuscitation facilitates successful defibrillation, improves hemodynamics postdefibrillation, decreases refibrillation, and thus improves survival after cardiac arrest. The effects are mediated through normalizing VF-induced dysfunctional calcium cycling.

Role of KATP channels in the maintenance of ventricular fibrillation in cardiomyopathic human hearts.

RATIONALE: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. OBJECTIVE: We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. METHODS AND RESULTS: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 µmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia). CONCLUSIONS: K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.

Intrinsic neural reflexes in the post-transplant human heart.

Radiofrequency ablation of post-transplant flutter in a centrally denervated donor atrium at a site remote from the AV node resulted in transient worsening of AV nodal conduction, with absent central vagal reinnervation. This could be an electrophysiological marker of intact innervation to the donor AV node from the intrinsic cardiac neuronal plexus, not demonstrated in human hearts earlier.

Cardiac stimulation with high voltage discharge from stun guns.

The ability of an electrical discharge to stimulate the heart depends on the duration of the pulse, the voltage and the current density that reaches the heart. Stun guns deliver very short electrical pulses with minimal amount of current at high voltages. We discuss external stimulation of the heart by high voltage discharges and review studies that have evaluated the potential of stun guns to stimulate cardiac muscle. Despite theoretical analyses and animal studies which suggest that stun guns cannot and do not affect the heart, 3 independent investigators have shown cardiac stimulation by stun guns. Additional research studies involving people are needed to resolve the conflicting theoretical and experimental findings and to aid in the design of stun guns that are unable to stimulate the heart.

Radiofrequency catheter ablation of a posteroseptal accessory pathway along the morphologic tricuspid valve in a patient with congenitally corrected transposition of the great arteries and complete atrioventricular block.

We report a patient with Congenitally Corrected Transposition of the Great Arteries, complete atrioventricular block and a posteroseptal accessory pathway across the morphologic tricuspid valve. Ablation of the accessory pathway was performed for her symptomatic palpitations.