A study of the role of nitric oxide in the mechanism of action of hydroalcoholic extract of saffron (Crocus sativus) on the electrophysiological properties of the rabbit atrioventricular node

Biologically active substances of plant origin represent an essential branch of modern cardiovascular pharmacotherapy. Furthermore, drugs of plant origin have the advantage of weaker adverse effects and lower prices than synthetic drugs. Pharmacological studies and traditional medical literature point to the anti-ischemic and hypotensive effects of the Crocus sativus L. (Iridacea). The major goals of the present study were: (1) to determine the negative dormotrophic properties of a hydroalcoholic extract of saffron on an isolated AV node and (2) to establish the role of nitric oxide in the mediating effects of saffron on the electrophysiological properties of the AV node. This was an experimental study. Selective stimulation protocols were used to independently quantify AV nodal recovery, facilitation and fatigue. We used isolated perfused rabbit AV node preparation, in three groups (N=32); in each group, we assessed the plant's effect in comparison with the control. In the pilot study, we used different concentrations (A=9 x 10-2 mg/L, B=19 x 10-2 mg/L and C=27 x 10-2 mg/L) to select the optimum concentration (19 x 10-2 mg/L) of the hydroalcoholic extract of saffron. Saffron has a depressant effect on basic and rate-dependent properties of the AV node. We observed an increasing AVCT (38.8 ±4 to 41.7 ±4 msec) and FRP (157.6 ±3 to 163.7 ±4 msec). Also saffron increased the amount of facilitation and the magnitude of fatigue (5.9 ±0.3 to 11.1 ±1 msec). The NOS inhibitor (L-NAME) has a preventative effect on the depressant effect of saffron on AVCT and FRP

Arrhythmia induction using isoproterenol or epinephrine during electrophysiology study for supraventricular tachycardia

Background Electrophysiology study (EPS) is an important part of the diagnosis and workup for supraventricular tachycardia (SVT). Provocative medications are used to induce arrhythmias, when they are not inducible at baseline. The most common medication is the β1‐specific agonist, isoproterenol, but recent price increases have resulted in a shift toward the nonspecific agonist, epinephrine. Objective We hypothesize that isoproterenol is a better induction agent for SVT during EPS than epinephrine. Methods We created a retrospective cohort of 131 patients, who underwent EPS and required medication infusion with either isoproterenol or epinephrine for SVT induction. The primary outcome was arrhythmia induction. Results Successful induction was achieved in 71% of isoproterenol cases and 53% of epinephrine cases (P = 0.020). Isoproterenol was significantly better than epinephrine for SVT induction during EPS (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.14‐4.85; P = 0.021). There was no difference in baseline variables or complications between the two groups. Other variables associated with successful arrhythmia induction included a longer procedure duration and atrioventricular nodal re‐entry tachycardia as the clinical arrhythmia. In a multivariable model, isoproterenol remained significantly associated with successful induction (OR, 2.57; 95% CI, 1.002‐6.59; P = 0.05). Conclusions Isoproterenol was significantly better than epinephrine for SVT arrhythmia induction. However, epinephrine was safe and successfully induced arrhythmias in the majority of patients who received it. Furthermore, when atropine was added in epinephrine‐refractory cases, in a post hoc analysis there was no difference in arrhythmia induction between medications. Cost savings could thus be significant without compromising safety

Influence of Atrioventricular Nodal Reentrant Tachycardia Ablation on Right to Left Inter-atrial Conduction

Background: Radiofrequency (RF) catheter ablation is the procedure of choice for the potential cure of atrioventricular nodal reentrant tachycardia (AVNRT) with high success rates. We hypothesed that as a result of the close proximity of Koch’s triangle and low inter-atrial septal fibers, the RF ablation applied at this region may result in prolongation of inter-atrial conduction time (IACT). Methods: RF ablation of AVNRT was performed by conventional technique. IACT was measured before and 20 minutes after RF ablation during sinus rhythm. Number of ablations given and duration of ablation were noted. Results: The study group was consisted of 48 patients (36 [75%] female, 12 [25%] male, mean age 43.4 ± 14. 5 years). RF ablation was successful in all patients. Mean RF time was 4. 0 ± 3. 3 minutes and mean number of RF was 11. 9 ± 9, 8. The mean IACT was 70.1 ± 9.0 ms before ablation and 84.9 ± 12.7 ms after ablation, which demonstrated a significant prolongation (p<0.001). The prolongation of IACT was very well correlated with the number of (r=0.897, p<0.001) and duration of RF (r=0.779; p<0.001). Conclusions: RF ablation of AVNRT results in prolongation of IACT. The degree of prolongation is associated with the duration and number of RF ablations given. The relationship between this conduction delay and late arrhythmogenesis need to be evaluated

Techniques for Identification of Left Ventricular Asynchrony for Cardiac Resynchronization Therapy in Heart Failure

The most recent treatment option of medically refractory heart failure includes cardiac resynchronization therapy (CRT) by biventricular pacing in selected patients in NYHA functional class III or IV heart failure. The widely used marker to indicate left ventricular (LV) asynchrony has been the surface ECG, but seems not to be a sufficient marker of the mechanical events within the LV and prediction of clinical response. This review presents an overview of techniques for identification of left ventricular intra- and interventricular asynchrony. Both manuscripts for electrical and mechanical asynchrony are reviewed, partly predicting response to CRT. In summary there is still no gold standard for assessment of LV asynchrony for CRT, but both traditional and new echocardiographic methods have shown asynchronous LV contraction in heart failure patients, and resynchronized LV contraction during CRT and should be implemented as additional methods for selecting patients to CRT

Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study

Oscillatory behavior of P wave duration and PR interval in experimental congestive heart failure: a preliminary study

Objective: The relationship between the autonomic nervous system (ANS) modulation of the sinus node and heart rate variability has been extensively investigated. The current study sought to evaluate, in an animal experimental model of pacing-induced tachycardia congestive heart failure (CHF), a possible ANS influence on the P wave duration and PR interval oscillations. Approach: Short-term (5 min) time and frequency domain analysis has been obtained in six dogs for the following electrocardiographic intervals: P wave duration (P), from the onset to peak of P wave (P p), from the onset of P wave to the q onset (PR) and from the end of P wave to the onset of q wave (P e R). Direct vagal nerve activity (VNA), stellate ganglion nerve activity (SGNA) and electrocardiogram (ECG) intervals have been evaluated contextually by implantation of three bipolar recording leads. Main results: At the baseline, multiple regression analysis pointed out that VNA was strongly positively associated with the standard deviation of PP and P e R intervals (r 2:0.997, p < 0.05). The same variable was also positively associated with high-frequency (HF) of P expressed in normalized units, of P p, and of P e R (b: 0.001) (r 2: 0.993; p < 0.05). During CHF, most of the time and frequency domain variability significantly decreased from 20% to 50% in comparison to the baseline values (p < 0.05) and SGNA correlated inversely with the low frequency (LF) obtained from P e R (p < 0.05) and PR (p < 0.05) (r 2:0.899, p < 0.05). LF components, expressed in absolute and normalized power, obtained from all studied intervals, were reduced significantly during CHF. Any difference between the RR and PP spectral components was observed. Significance: The data showed a significant relationship between ANS and atrial ECG variables, independent of the cycle duration. In particular, the oscillations were vagal mediated at the baseline, while sympathetic mediated during CHF. Whereas P wave variability might have a clinical utility in CHF management, it needs to be addressed in specific studies

An atrioventricular node model incorporating autonomic tone

The response to atrial fibrillation (AF) treatment is differing widely among patients, and a better understanding of the factors that contribute to these differences is needed. One important factor may be differences in the autonomic nervous system (ANS) activity. The atrioventricular (AV) node plays an important role during AF in modulating heart rate. To study the effect of the ANS-induced activity on the AV nodal function in AF, mathematical modelling is a valuable tool. In this study, we present an extended AV node model that incorporates changes in autonomic tone. The extension was guided by a distribution-based sensitivity analysis and incorporates the ANS-induced changes in the refractoriness and conduction delay. Simulated RR series from the extended model driven by atrial impulse series obtained from clinical tilt test data were qualitatively evaluated against clinical RR series in terms of heart rate, RR series variability and RR series irregularity. The changes to the RR series characteristics during head-down tilt were replicated by a 10% decrease in conduction delay, while the changes during head-up tilt were replicated by a 5% decrease in the refractory period and a 10% decrease in the conduction delay. We demonstrate that the model extension is needed to replicate ANS-induced changes during tilt, indicating that the changes in RR series characteristics could not be explained by changes in atrial activity alone

Pacemaker Prevention Therapy in Drug–refractory Paroxysmal Atrial Fibrillation: Reliability of Diagnostics and Effectiveness of Prevention Pacing Therapy in Vitatron™ Selection® device

Introduction. Atrial fibrillation (AF), the most common and rising disorder of cardiac rhythm, is quite difficult to control and/or to treat. Non pharmacological therapies for AF may involve the use of dedicated pacing algorithms to detect and prevent atrial arrhythmia that could be a trigger for AF onset. Selection 900E/AF2.0 Vitatron DDDRP pacemaker (1) keeps an atrial arrhythmia diary thus providing detailed onset reports of arrhythmias of interest, (2) provides us data about the number of premature atrial contractions (PACs) and (3) plots heart rate in the 5 minutes preceding the detection of an atrial arrhythmia. Moreover, this device applies four dedicated pacing therapies to reduce the incidence of atrial arrhythmia and AF events. Aim of the Study. To analyze the reliability to record atrial arrhythmias and evaluate effectiveness of its AF preventive pacing therapies. Material and Methods. We enrolled 15 patients (9 males and 6 females, mean age of 71±5 years, NYHA class I–II), with a DDDRP pacemaker implanted for a “bradycardia–tachycardia” syndrome, with advanced atrioventricular conduction disturbances. We compared the number and duration of AF episodes’ stored in the device with a contemporaneous 24h Holter monitoring. After that, we switched on the atrial arrhythmias detecting algorithms, starting from an atrial rate over 180 beats per minute for at least 6 ventricular cycles, and ending with at least 10 ventricular cycles in sinus rhythm. Thereafter, in order to evaluate the possible reduction in PACs number and in number and duration of AF episodes, we tailored all the four pacing preventive algorithms. Patients were followed for 24±8 months (from 20 to 32 months). Results. All 59 atrial arrhythmia episodes occurred in the first part of this trial, were correctly recorded by both systems, with a correlation coefficient (r) of 0.96. During the follow–up, we observed a significant reduction not only in PACs number (from 83±12/day to 2.3±0.8/day) but also in AF episodes (from 46±7/day to 0.12±0.03/day) and AF burden (from 93%±6% to 0.3%±0.06%). An increase in atrial pacing percentages (from 3%±0.5% to 97%±3%) was also contemporaneously observed. Conclusion. In this pacemaker, detection of atrial arrhythmia episodes is highly reliable, thus making available an appropriate monitoring of heart rhythm, mainly suitable in AF asymptomatic patients. Moreover, the significant reduction of atrial arrhythmia episodes indicates that this might represent a suitable therapeutic option for an effective preventive therapy of AF in paced brady–tachy patients

Atrioventricular and interventricular delay optimization in cardiac resynchronization therapy: physiological principles and overview of available methods

In this review, the physiological rationale for atrioventricular and interventricular delay optimization of cardiac resynchronization therapy is discussed including the influence of exercise and long-term cardiac resynchronization therapy. The broad spectrum of both invasive and non-invasive optimization methods is reviewed with critical appraisal of the literature. Although the spectrum of both invasive and non-invasive optimization methods is broad, no single method can be recommend for standard practice as large-scale studies using hard endpoints are lacking. Current efforts mainly investigate optimization during resting conditions; however, there is a need to develop automated algorithms to implement dynamic optimization in order to adapt to physiological alterations during exercise and after anatomical remodeling