Ventricular Fibrillation Threshold Research Articles

2 * Beta-blockers do not prevent the pro-arrhythmic action of high-level sympathetic stimulation: a role for neuropeptide Y?

Introduction: Beta-blockers (BB) are the only anti-arrhythmic drugs that improve mortality in patients with ischaemic heart disease, but a significant risk of arrhythmia remains. During high-level sympathetic drive, such as during myocardial infarction, co-transmitters including neuropeptide Y (NPY) can be released with norepinephrine. NPY is a potent vasoconstrictor that can also alter cardiac electrophysiology. We hypothesised that ventricular fibrillation threshold (VFT) would still be reduced following high-level sympathetic stimulation even in the presence of a BB. We also investigated whether NPY is independently pro-arrhythmic and decreases VFT, and if this mechanism is mediated by the Y1 receptor. Methods: Hearts with intact stellate ganglia (SG) and sympathetic innervation were isolated from male Sprague Dawley rats (250-300g) and Langendorff perfused in constant flow mode. VFT was determined by pacing at a fixed cycle length (150ms x 20 beats) followed by a 5sec 50Hz burst at increasing current amplitude (mA) until sustained VF was induced. VF was cardioverted with 1ml of potassium chloride solution (50mmol/L). A control experiment demonstrated that VFT remained constant over 3 successive inductions (n=6). SG were stimulated at 10Hz, 1msec pulse width (above capture voltage). Drugs were perfused for 15 minutes before stimulation. Electrical restitution (RT) was derived from optically mapped action potentials (RH237, 15 µL of 5mg/mL) in the presence of blebbistatin (10 µmol/L). All data are presented as mean±standard error. Results: Direct SG stimulation significantly (p<0.05) increased heart rate and left ventricular developed pressure (LVDP) and these changes were completely blocked by metoprolol (10 µmol/L). However, 2 mins of right SG stimulation in the presence of metoprolol still significantly reduced VFT (2.2±0.0.49 vs. 1.2±.0.26mA, n=6). VFT was also decreased by norepinephrine (1 µmol/L), however this effect was abolished by metoprolol (n=4). NPY (250nmol/L, n=6) mimicked the effect of SG stimulation and significantly reduced VFT by 50% (2.4±0.15 vs 1.2±0.12mA) and increased coronary vascular resistance and LVDP. The action of NPY on VFT, CVR and LVDP were abolished by the Y1 receptor antagonist BIBO3304 (1 µM, n=6). Preliminary analysis of RT by optical mapping is suggestive of a steepening of the curve with NPY 250nM (0.27±0.04 vs NPY 0.42±0.12). The Y1 receptor antagonist BIBO3304 (1 µM, n=6) also prevented the reduction in VFT in response to SG stimulation in the presence of metoprolol. Conclusion: Prolonged sympathetic stimulation remains pro-arrhythmic in the presence of BB, implicating sympathetic co-transmitters as a novel arrhythmic trigger. NPY can directly decrease VFT via a Y1 receptor mediated mechanism that steepens the RT curve. A combination of BB and Y1 receptor blockade is able to fully prevent the pro-arrhythmic action of prolonged sympathetic stimulation.

GW25-e0091 Effects of Cardiac Stem Cells Transplantation on the Ventricular Fibrillation Threshold in Rats with Myocardial Infarction in Short-Term, Medium-Term and Long-Term Period

Arrhythmia is of concern after cardiac stem cells (CSCs) transplantation in repairing infarcted myocardium. However, whether transplanted CSCs improved ventricular fibrillation threshold (VFT) in the myocardial infarction model is still unclear. We sought to investigate the VFT in rats with

Limitations of animal electrical cardiac safety models.

Human electrical safety standards are based almost exclusively on animal studies and there is an unjustified assumption that ventricular fibrillation (VF) thresholds in animals are the same as those in humans. We analyzed differences between animals and humans in cardiac stimulation. A broad literature survey revealed that swine are a fragile electrophysiologic research species and have a dense intramural Purkinje fiber network, which is not found in some other species, including humans. Anesthesia agents have to be chosen carefully as swine are prone to malignant hyperthermia. Cardiac stimulation thresholds depend on weight and capture rates. Thus, the animal weight has to be representative of the weight of human subjects. Studies have shown significant ECG differences between humans and other species, including swine and canine. At least one study suggested that rabbit hearts tend to develop VF in a manner more similar to that seen in humans. Animal studies can play a role in conservatively evaluating cardiac safety. However, while still abiding by the precautionary principle, animal study design has to take into account the significant anatomical and electrophysiological differences between humans and other mammals. Data from multiple animal models may offer broader perspectives. If attempts are made to extrapolate animal results to humans then appropriate numerical correction factors should be applied, such as some of those discussed in this article.

Artemisinin prevents electric remodeling following myocardial infarction possibly by upregulating the expression of connexin 43.

Artemisinin has been demonstrated to exert beneficial effects on ventricular remodeling. The present study investigated whether artemisinin was able to decrease the ventricular fibrillation threshold (VFT) in rats following myocardial infarction (MI) and aimed to determine the possible underlying mechanisms. The rats were subjected to surgery to induce MI by ligation of the left anterior descending artery and were randomly allocated to receive vehicle or artemisinin (75 mg/kg/day) treatment for four weeks. Programmed electrical stimulation demonstrated a significantly increased VFT in the artemisinin-treated group compared with the vehicle-treated group. The electrophysiological improvement of the VFT was accompanied by increased immunofluorescence-stained connexin 43 (Cx43), myocardial Cx43 protein and mRNA levels in artemisinin-treated rats. The present study also demonstrated that artemisinin significantly decreased tissue tumor necrosis factor (TNF)-α levels at the infarcted border zone. Thus, artemisinin demonstrated a protective effect on ventricular arrhythmias following MI. Although the precise mechanism by which artemisinin modulates the dephosphorylation of Cx43 is unknown, it is likely that artemisinin increased the expression of Cx43 via the inhibition of TNF-α.

Fosinopril improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats.

This study investigated the effects of fosinopril on the electrophysiological characteristics of the left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHRs). Twenty-four 10-week-old male SHRs were divided into fosinopril and non-fosinopril groups (n = 12 each). Twelve 10-week-old Wistar-Kyoto rats were used a control group. Left ventricular mass index and ventricular fibrillation threshold (VFT) were measured after 8 weeks of fosinopril or saline treatment. L-type calcium current (I CaL), sodium current (I Na), and transient outward potassium current (I to) were measured in left ventricular myocytes after 8 weeks of fosinopril or saline treatment using the whole-cell patch-clamp technique. VFT was higher in the fosinopril group than in the non-fosinopril group (17.5 ± 1.2 mA vs. 15.6 ± 1.1 mA, P < 0.01). The density of I CaL was lower in the fosinopril group than in the non-fosinopril group (-7.17 ± 0.13 pA/pF vs. -7.87 ± 0.13 pA/pF, P < 0.05). The density of I to was higher in the fosinopril group than in the non-fosinopril group (14.46 ± 0.28 pA/pF vs. 12.66 ± 0.25 pA/pF, P < 0.05). I to was positively correlated with VFT (r = 0.90, P < 0.001) and was found to be associated independently with VFT (P < 0.001). Fosinopril improves the electrophysiological characteristics of the left ventricular hypertrophic myocardium in SHRs.

Устойчивость физиологических функций и методы ее оценки

Problem of physiological functions stability is the important part of the theoretical physiology. P.K.Anohin&amp;#180;s basic ideas - the theory of functional systems and systemic approach to study of physiological functions have begun the development of theoretical physiology and mathematical modeling in biomedicine. In this paper methodological aspects of using of various biomodels for an estimation of stability of physiological functions are considered. Experimental, genetic, mathematical and computer biomodels are described. Practical techniques of an estimation of stability are illustrated on an example of stability of cardiovascular functions to stressor loads. Examples of different experimental models of stress and methods of estimation of stressor loads influence on cardiac electrical stability are described. Cardiac electrical stability was estimated by thresholds for ventricular fibrillation. Besides experimental, examples of mathematical and computer methods of an estimation of stability of cardiovascular functions to stressor loads are presented. Mathematical model that enables to investigate the stability of heart rate dynamics to stressor loads is based on quantitative characteristics of impulse conduction in heart conducting system. The model describes the phenomena observed at gradual increase of stressor intensity. It was shown the existence of a critical point of transition of heart rate dynamics from linear to chaotic mode. The results show that the greatest stability is notable for the linear regime. For this regime small errors in values of initial conditions can’t sharply change the initial dynamics of RR intervals.

Optical Mapping of Sarcoplasmic Reticulum Ca 2+ in the Intact Heart

Rationale: Sarcoplasmic reticulum (SR) Ca 2+ cycling is key to normal excitation–contraction coupling but may also contribute to pathological cardiac alternans and arrhythmia. Objective: To measure intra-SR free [Ca 2+ ] ([Ca 2+ ] SR ) changes in intact hearts during alternans and ventricular fibrillation (VF). Methods and Results: Simultaneous optical mapping of V m (with RH237) and [Ca 2+ ] SR (with Fluo-5N AM) was performed in Langendorff-perfused rabbit hearts. Alternans and VF were induced by rapid pacing. SR Ca 2+ and action potential duration (APD) alternans occurred in-phase, but SR Ca 2+ alternans emerged first as cycle length was progressively reduced (217±10 versus 190±13 ms; P &lt;0.05). Ryanodine receptor (RyR) refractoriness played a key role in the onset of SR Ca 2+ alternans, with SR Ca 2+ release alternans routinely occurring without changes in diastolic [Ca 2+ ] SR . Sensitizing RyR with caffeine (200 μmol/L) significantly reduced the pacing threshold for both SR Ca 2+ and APD alternans (188±15 and 173±12 ms; P &lt;0.05 versus baseline). Caffeine also reduced the magnitude of spatially discordant SR Ca 2+ alternans, but not APD alternans, the pacing threshold for discordance, or threshold for VF. During VF, [Ca 2+ ] SR was high, but RyR remained nearly continuously refractory, resulting in minimal SR Ca 2+ release throughout VF. Conclusions: In intact hearts, RyR refractoriness initiates SR Ca 2+ release alternans that can be amplified by diastolic [Ca 2+ ] SR alternans and lead to APD alternans. Sensitizing RyR suppresses spatially concordant but not discordant SR Ca 2+ and APD alternans. Despite increased [Ca 2+ ] SR during VF, SR Ca 2+ release was nearly continuously refractory. This novel method provides insight into SR Ca 2+ handling during cardiac alternans and arrhythmia.

Valsartan improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats.

The objective was to investigate the effects of valsartan on the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rats (SHR). A total of 24 10-week-old male SHR were divided into two groups: valsartan and non-valsartan groups (n=12 in each). Twelve 10-week-old Wistar-Kyoto rats were served as the control group. Kv4.2 expression was measured in left ventricular myocardium using western blots. In addition, the systolic blood pressure, left ventricular mass index (LVMI), ventricular effective refractory period and ventricular fibrillation threshold (VFT) were also measured after eight weeks. INa, ICaL, Ito and membrane capacitance were measured in left ventricular myocytes after 8 weeks by whole-cell patch clamp. Valsartan decreased LVMI compared with the non-Valsartan group (Valsartan vs. non-Valsartan: 3.2±0.03 mg g(-1) vs. 3.7±0.02 mg g(-1), P<0.01). Valsartan also enhanced the VFT compared with the non-Valsartan group (Valsartan vs. non-Valsartan: 18.6±0.3 mA vs. 15.4±0.4 mA, P<0.01). The expression of Kv4.2 was significantly lower in the non-Valsartan and Valsartan groups compared with the control group (P<0.01). The expression of Kv4.2 was significantly higher in the Valsartan group compared with the non-Valsartan group (P<0.01). Valsartan decreased the density of ICaL compared with non-Valsartan group (Valsartan vs. non-Valsartan: -5.5±0.6 pA/pF vs. -7.2±0.9 pA/pF, P<0.05). Valsartan improved the density of Ito compared with non-Valsartan group(Valsartan vs. non-Valsartan: 13.93±0.8 pA/pF vs. 11.22±1.0 pA/pF, P<0.05). Valsartan improves the electrophysiological characteristics of left ventricular hypertrophic myocardium in spontaneously hypertensive rat.

Cardiac Changes Due to Electronic Control Devices? A Computer‐Based Analysis of Electrical Effects at the Human Heart Caused by an ECD Pulse Applied to the Body's Exterior

Electronic control devices (ECDs) deliver high-voltage, low-current energy pulses temporarily paralyzing a person. For the ECD-human interaction, we have developed a computer model using the SEMCAD program within which to simulate the electrical effects throughout the body resulting from the imposition of an ECD pulse at a particular point on the body surface. Our human body models were based on cross-sectional MRIs and CT scans, with the dielectric properties of the various tissues assigned based on previously published values. We simulated the application of a single ECD pulse and calculated the resulting electric field strength and current and charge densities at different body locations. The results were compared with corresponding values obtained by other researchers in similar simulations. Furthermore, we simulated an application of a pulse of 20-millisecond duration equal to the European household current of 50 Hz and to the ventricular fibrillation threshold. The resulting current level indicated at the heart muscle was 1/5 the level considered the threshold for triggering ventricular fibrillation.

STUDY CARDIOTOXIC PROPERTIES OF NATIVE PEAT HUMIC ACIDS

The earlier pathomorphological studies of toxic properties of peat humic acids (PHAs) at intraperitoneal injection revealed that one of the causes of lethality is the direct cardiotoxic action of PHAs. For the further study of the mechanism of cardiotoxic action, electrocardiogram was recorded and ventricular fibrillation threshold was determined in male rats after intraperitoneal injection of humic acids in knowingly lethal dose – 480 mg/kg bwt. A single intraperitoneal injection of PHA to rats in knowingly lethal dose caused a significant decrease of the ventricular fibrillation threshold in comparison with intact animals. It was found that the PHA injection exerted no significant effect on the heart rate in rats and change of the PQ, QT, and QTc intervals. At the same time, the significant shortening of the QRS complex in comparison with intact animals was observed. Judging from the results obtained, the single injection of humic acids in the lethal dose induced a decrease in the electrical stability of heart, as evidenced by the drop of the ventricular fibrillation threshold. This decrease of the electrical stability of heart can be a cause of sudden cardiac death of trial rats. Disorder of the heart electrical stability is likely connected with the ionophoric action of humic acids and change of electrophysiological properties of cell membranes.

Cardiac contractility modulation increases action potential duration dispersion and decreases ventricular fibrillation threshold via β1-adrenoceptor activation in the crystalloid perfused normal rabbit heart

Background/objectivesCardiac contractility modulation (CCM) is a new treatment being developed for heart failure (HF) involving application of electrical current during the absolute refractory period. We have previously shown that CCM increases ventricular force through β1-adrenoceptor activation in the whole heart, a potential pro-arrhythmic mechanism. This study aimed to investigate the effect of CCM on ventricular fibrillation susceptibility. MethodsExperiments were conducted in isolated New Zealand white rabbit hearts (2.0–2.5kg, n=25). The effects of CCM (±20mA, 10ms phase duration) on the left ventricular basal and apical monophasic action potential duration (MAPD) were assessed during constant pacing (200bpm). Ventricular fibrillation threshold (VFT) was defined as the minimum current required to induce sustained VF with rapid pacing (30×30ms). Protocols were repeated during perfusion of the β1-adrenoceptor antagonist metoprolol (1.8μM). In separate hearts, the dynamic and spatial electrophysiological effects of CCM were assessed using optical mapping with di-4-ANEPPS. ResultsCCM significantly shortened MAPD close to the stimulation site (Basal: 102±5 [CCM] vs. 131±6 [Control] ms, P<0.001). VFT was reduced during CCM (2.6±0.6 [CCM] vs. 6.1±0.8 [Control] mA, P<0.01) and was correlated (r2=0.40, P<0.01) with increased MAPD dispersion (26±4 [CCM] vs. 5±1 [Control] ms, P<0.01) (n=8). Optical mapping revealed greater spread of CCM induced MAPD shortening during basal vs. apical stimulation. CCM effects were abolished by metoprolol and exogenous acetylcholine. No evidence for direct electrotonic modulation of APD was found, with APD adaptation occurring secondary to adrenergic stimulation. ConclusionsCCM decreases VFT in a manner associated with increased MAPD dispersion in the crystalloid perfused normal rabbit heart.

Aliskiren ameliorates sympathetic nerve sprouting and suppresses the inducibility of ventricular tachyarrhythmia in postinfarcted rat heart

Background Aliskiren is an oral renin inhibitor, which inhibits the first rate limiting step in the renin angiotensin aldosterone system. In this study, sympathetic nerve sprouting and the inducibility of ventricular fibrillation after aliskiren treatment in myocardial infarction were investigated. Methods Male Sprague Dawley rats after coronary artery ligation were randomly allocated to four groups: angiotensin converting enzyme inhibitor enalapril, angiotensin receptor blocker valsartan, β adrenergic receptor blocker carvedilol and rennin inhibitor aliskiren treatment for six weeks. Electrophysiological study, histological examination and Western blotting were performed. Results The plasma norepinephrine level and sympathetic nerve innervation significantly increased in treated infarcted rats compared to untreated rats. Aliskiren treatment reduced the sympathetic nerve innervations after myocardial infarction. There is no significant difference in sympathetic nerve innervations after myocardial infarction among the enalapril, valsartan, carvediloand or aliskiren treated groups. Programmed electrical stimulation study showed that inducible ventricular arrhythmia was reduced, ventricular fibrillation threshold was increased and ventricular effective refractory period was prolonged in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats compared to untreated infarcted rats. Cardiomyocytic apoptosis in infarcted region was significantly decreased in enalapril, valsartan, carvedilol and aliskiren treated infarcted rats. Conclusions Aliskiren ameliorated cardiomyocytic apoptosis, attenuated the sympathetic nerve innervations and reduced the vulnerability of ventricular arrhythmias after myocardial infarction. Enalapril, valsartan and carvedilol have similar effects as aliskiren on cardiomyocytic apoptosis, sympathetic nerve innervations and vulnerability of ventricular arrhythmias after myocardial infarction.

Peripheral cardiac sympathetic hyperactivity in cardiovascular disease: role of neuropeptides.

High levels of sympathetic drive in several cardiovascular diseases including postmyocardial infarction, chronic congestive heart failure and hypertension are reinforced through dysregulation of afferent input and central integration of autonomic balance. However, recent evidence suggests that a significant component of sympathetic hyperactivity may also reside peripherally at the level of the postganglionic neuron. This has been studied in depth using the spontaneously hypertensive rat, an animal model of genetic essential hypertension, where larger neuronal calcium transients, increased release and impaired reuptake of norepinephrine in neurons of the stellate ganglia lead to a significant tachycardia even before hypertension has developed. The release of additional sympathetic cotransmitters during high levels of sympathetic drive can also have deleterious consequences for peripheral cardiac parasympathetic neurotransmission even in the presence of β-adrenergic blockade. Stimulation of the cardiac vagus reduces heart rate, lowers myocardial oxygen demand, improves coronary blood flow, and independently raises ventricular fibrillation threshold. Recent data demonstrates a direct action of the sympathetic cotransmitters neuropeptide Y (NPY) and galanin on the ability of the vagus to release acetylcholine and control heart rate. Moreover, there is as a strong correlation between plasma NPY levels and coronary microvascular function in patients with ST-elevation myocardial infarction being treated with primary percutaneous coronary intervention. Antagonists of the NPY receptors Y1 and Y2 may be therapeutically beneficial both acutely during myocardial infarction and also during chronic heart failure and hypertension. Such medications would be expected to act synergistically with β-blockers and implantable vagus nerve stimulators to improve patient outcome.

Acetylcholine analogue mimics the protective effect of cardiac vagal nerve stimulation on ventricular fibrillation threshold

Purpose: Implantable cardiac vagus nerve stimulators are a promising new treatment for heart failure, which may improve both quality of life and ejection fraction. Animal studies also suggest an anti-fibrillatory effect of stimulating the cardiac vagus nerve that may involve a nitric oxide (NO) dependent pathway, although the exact site of action in the cardiac-neural axis is still debated. We investigated whether carbamylcholine (CCh), a stable analogue of the neurotransmitter acetylcholine, can mimic the effect of vagus nerve stimulation on ventricular fibrillation threshold (VFT), and whether this mechanism is dependent on muscarinic receptor stimulation and/or generation of NO. Methods: Experiments conformed to Principles of laboratory animal care (NIH Publication No. 85-23, revised 1996) and the Animals (Scientific Procedures) Act 1986 (UK). Hearts were isolated from adult male Sprague Dawley rats (300-350g) and Langendorff perfused with tyrode solution in constant flow mode (11ml/min, baseline perfusion pressure 54.75±7.27mmHg, LV developed pressure 77.5±5.6mmHg, heart rate 282.8±3.4bpm, n=6). VFT was reproducibly determined by pacing at a fixed cycle length (150msec) for 20 beats followed by a 5sec 50Hz burst at increasing current amplitude (mA) until sustained VF was induced. VF was cardioverted to sinus rhythm by perfusion with 1ml of high concentration potassium chloride solution (50mmol/L). All data are presented as mean±SEM with ANOVA for multiple comparisons. Results: CCh (200nM, n=9) significantly (p<0.05) reduced baseline heart rate from 292±8 to 224±6bpm). [In paced hearts] Independent of this heart rate change, CCh also caused a significant increase in VFT similar to vagus nerve stimulation that could be reversed with washout of the drug (control 1.5±0.25 vs. CCh 2.4±0.4 mA vs. wash out 1.14±0.18 mA). The effect of CCh on VFT was completely abolished by atropine (10μM, n=4) or the non-specific competitive NOS inhibitor N-omega-nitro-L-arginine (L-NA 100μM, n=6). The inhibitory action of L-NA could be reversed by the addition of the NOS substrate L-arginine (5mM). The NO donor sodium nitroprusside (SNP 10μM, n=8) mimicked the effects of CCh and significantly increased VFT (baseline 1.4±0.125 vs, SNP 2.9±0.83 vs. wash out 1.18±0.23 mA). Conclusions: These data demonstrate that the protective effect of cardiac vagal nerve stimulation on VFT is mimicked by CCh in the rat. Muscarinic receptor stimulation and the generation of NO appear to be involved in mediating this protective effect, presumably via a pre-synpatic and post synaptic coupled pathway.

GW24-e1863 The influence of benazepril hydrochloride on hypertensive left ventricular hypertrophy transmural heterogeneity of ventricular repolarisation

ObjectivesTo study the relationship of Benazepril on hypertensive left ventricular hypertrophy transmural repolarisation heterogeneity effects and inhibit ventricular arrhythmiasMethodsMaking hypertensive left ventricular hypertrophy model in rabbits, and to give Benazepril...

Cardiac sympathectomy in humans: Rationale, results & mechanistic insights

The autonomic nervous system plays a critical role in the genesis and maintenance of ventricular arrhythmias. Pharmacological anti-adrenergic interventions, such as beta-blockers are a cornerstone of therapeutic management of ventricular arrhythmias. However, ventricular arrhythmias that remain refractory to standard medical management are associated with a high mortality. Neuraxial modulation using thoracic epidural anesthesia (TEA) and surgical removal of the stellate ganglia and thoracic sympathetic ganglia (cardiac sympathetic denervation, CSD) are therapeutic options for such cases. The protective effects of CSD have been demonstrated in long QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia. CSD has also been shown to lengthen ventricular refractoriness and raise the ventricular fibrillation threshold without impairing cardiac contractility. Analysis of data from patients with VT refractory to medical therapy and catheter ablation referred for CSD between 4/2009 and 8/2012 was performed. Thirty eight patients (32 males, 6 females, age 60 ± 12 years, EF 30 ± 15%) with recurrent VT or VT underwent CSD. One patient was referred for idiopathic VF. Patients had experienced a median of 2 catheter ablation procedures and 13 (range 7-55) implantable cardiac defibrillator (ICD) shocks in the 6 months prior to the procedure. At a mean follow up of 356 ± 300 days (median = 160 days), 4 patients (12.5%) underwent heart transplantation and 15 (39%) patients died, two after heart transplantation, one after lead extraction, one from renal failure, and 11 from worsening heart failure or multi-organ failure. Incidence of recurrent arrhythmias from ICD logs was available in 31 patients (82%), 10 with left CSD and 21 with bilateral CSD. Three (30%) of the left CSD patients and 11 (52%) of bilateral CSD patients were completely free of ICD shocks (P < 0.05 for bilateral vs. left). Bilateral CSD demonstrates long-term benefit in reducing ICD shocks in patients with recurrent VT and cardiomyopathy refractory to medical therapy.

Forgotten electrical accidents and the birth of shockproof X-ray systems

ObjectivesTo commemorate victims of electrical accidents that occurred in the first decades of radiology and relate these accidents to the evolution of the X-ray apparatus.MethodsDigitised newspapers, scientific journals, books and reports of legal procedures were searched for electrical accidents involving X-ray systems. Information on the historical systems was retrieved from the scientific literature and brochures from manufacturers.ResultsWe found 51 fatal and 62 non-fatal but serious electrical accidents. Most of them occurred between 1920 and 1940 and involved transformers that provided output currents well above the threshold for the induction of ventricular fibrillation. The accidents led to recommendations and regulations to improve safety for operators and patients, and spurred manufacturers to technical developments that culminated in fully electrically shockproof systems by 1935.ConclusionsAlthough largely forgotten, the development of the shockproof X-ray systems we take for granted today lasted about 4 decades and was associated with considerable human suffering. The complete solution of the problem is a success story of engineering realised by contributions from all parties involved.Main messages• The development of electrically shockproof X-ray systems took about 4 decades (1895–1935).• Between 1896 and 1920 electrical shocks from X-ray systems were common, but their consequences limited.• After 1920, transformers killed by delivering currents above the ventricular fibrillation threshold.• Inductors, static generators and high-frequency coils were generally low-current systems and safe.• We found 51 fatal and 62 serious non-fatal electrical accidents, most occurring from 1920 to 1940.Electronic supplementary materialThe online version of this article (doi:10.1007/s13244-013-0238-8) contains supplementary material, which is available to authorised users.

Effects of hypokalemia on transmural dispersion of ventricular repolarization in left ventricular myocardium

ObjectiveTo observe effects of hypokalemia on transmural heterogeneity of ventricular repolarization in left ventricular myocardium of rabbit, and explore the role of hypokalemia in malignant ventricular arrhythmia (MVA). MethodsA total of 20 rabbits were randomly divided into control group and hypokalemic group. Isolated hearts in the control group were simply perfused with modified Tyrode's solution, and were perfused with hypokalemic Tyrode's solution in hypokalemic group. Ventricular fibrillation threshold (VFT), 90% monophasic action potential repolarization duration (APD90) of subepicardial, midmyocardial and subendocardial myocardium, transmural dispersion of repolarization (TDR) and C×43 protein expression in three layers of myocardium were measured in both groups. ResultsVFT in the control group and the hypokalemic group were (13.40±2.95) V, and (7.00±1.49) V, respectively. There was a significant difference between two groups (P<0.01). APD90 of three myocardial layers in the hypokalemic group were significantly prolonged than those in the control group (P<0.01). ΔAPD90 in the hypokalemic group and the control group were (38.10±10.29) ms and (23.70±5.68) ms, and TDR were (52.90±14.55) ms and (36.10±12.44) ms, respectively. ΔAPD90 and TDR in the hypokalemic group were significantly higher than those in the control group (P<0.05), and the increase in APD90 of midmyocardium was more significant in the hypokalemic group. Cx43 protein expression of all three myocardial layers were decreased significantly in the hypokalemic group (P<0.01), and ΔCx43 was significantly increased (P<0.05). Reduction of Cx43 protein expression was more significant in the midmyocardium. ConclusionsHypokalemic can increase transmural heterogeneity of C×43 expression and repolarization in left ventricular myocardium of rabbit, and decrease VFT and can induce MVA more easily.

研究会 第22回 理論心電図研究会 心室細胞閾値をめぐる諸問題 電気的心室細動閾値測定法の問題点

研究会 第22回 理論心電図研究会 心室細胞閾値をめぐる諸問題 電気的心室細動閾値測定法の問題点

The Antifibrillatory Effects of Vagus Nerve Stimulation in the Rabbit Ventricle involves cGMP‐Dependent Mechanisms

We have previously shown that vagus nerve stimulation (VNS) increases effective refractory period (ERP) and ventricular fibrillation threshold (VFT) whilst reducing electrical restitution slope, via an acetycholine independent ‐ nitric oxide (NO) dependent mechanism. NO activates soluble guanylyl cyclase [sGC] to produce cyclic guanylyl monophosphate (cGMP) to modulate cardiac function. Our aim was to investigate if the effects of the VNS‐NO pathway on ERP, VFT and restitution slope were mediated via cGMP mechanisms. The innervated rabbit heart was used (n=5, 2.5–3kg) in constant flow Langendorff mode. Ventricular ERP was determined using a single extrastimulus protocol (300ms cycle length) and maximal restitution slope was measured. VFT was the minimum current needed to induce sustained VF with burst pacing (30×30ms). These were measured at baseline [BL] and during VNS [10Hz, 9V] in control (Ctrl) and following sGC inhibition with (1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one [ODQ], 10μM). Data are mean±SEM, Student's T‐Test, P&lt;0.05 * vs BL, ** vs Ctrl. VNS increased ERP and VFT whilst reducing restitution slope. During sGC inhibition, the vagal effect on restitution slope and VFT were reduced, whilst the effect on ERP was preserved. Cyclic GMP is involved in the protective effects of VNS‐NO pathway against VF but concurrent cGMP independent mechanisms could also be at work. KEB is supported by a British Heart Foundation IBSR Fellowship Table ERP (ms) Slope VFT (mA) Ctrl BL 131.0±3.3 1.48±0.2 3.6 ±0.7 Ctrl VNS 158.0±9.3* 0.99±0.21* 7.0±0.6* Change 16.8±5.9 −0.5±0.1 3.4±0.2 ODQ BL 144.2±4.5 1.3±0.1 3.5±0.7 ODQ VNS 159.0±7.6* 1.2±0.1 5.2±0.8* Change 12.0±3.0 −0.1±0.1** 1.7±0.1**