Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.     

Sensors for Caspase Activities

Cysteine proteases, caspases, play an important role in the process of programmed cell death. In apoptosis, the cell signaling pathways overlap at executioner caspases regardless of the initial stimulus. Caspase-3 is the key one. This review considers the sensors for activity of caspase-3 and some other caspases. Over the past decade, many such sensors utilizing a variety of detection principles have been created; fluorescence and luminescence are the most common detection methods. The intracellular sensors are of particular interest; they allow visualization of the activation of caspases in living systems. Herein, we briefly describe sensors of various designs, the advantages and disadvantages of which must be taken into account when choosing a sensor for a particular experimental system.

     

Mechanisms underlying adaptation of action potential duration by pacing rate in rat myocytes

Heart rate is an essential determinant of cardiac performance. In rat ventricular myocytes, a sudden increase in rate yields to a prolongation of the action potential duration (APD). The mechanism underlying this prolongation is controversial: it has been proposed that the longer APD is due to either: (1) a decrease in K⁺ currents only or (2) an increase in Ca²⁺ current only. The aim of this study was to quantitatively investigate the contribution of Ca²⁺ and K⁺ currents in the adaptation of APD to pacing rate. Simulation using a mathematical model of ventricular rat cardiac cell model [Pandit, S.V., Clark, R.B., Giles, W.R., Demir, S.S., 2001. A mathematical model of action potential heterogeneity in adult rat left ventricular myocytes. Biophys. J. 81, 3029–3051] predicted a role in the prolongation of APD for K⁺ currents only. In patch clamp experiments, increasing the pacing rate leads to a significant increase in APD in both control and detubulated myocytes, although it was more marked in control than detubulated myocytes. Supporting the model prediction, we observed that increasing stimulation frequency leads to a decrease in K⁺ currents in voltage clamped rat ventricular myocytes (square and action potential waveforms), and to a similar extent in both cell types. We have also observed that frequency-dependent facilitation of Ca²⁺ current occurred in control cells but not in detubulated cells (square and action potential waveforms). From these experiments, we calculated that the relative contribution of Ca²⁺ and K⁺ currents to the longer APD following an increase in pacing rate is 65% and 35%, respectively. Therefore, in contrast to the model prediction, Ca²⁺ current has a significant role in the adaptation of APD to pacing rate. Finally, we have introduced a simplistic modification to the Pandit's model to account for the frequency-dependent facilitation of Ca²⁺ current.     

Atrial pacing, the forgotten pacing mode

In patients with sick sinus syndrome and normal atrioventricular conduction, physiological pacing can be accomplished with either a single chamber atrial pacemaker AAI/R or a dual chamber pacemaker DDD/R. The single chamber device has the advantages of simpler implantation and lower initial costs, while the dual chamber device offers protection in case atrioventricular conduction disturbances develop in the future. When rigorous attention is paid to the pre-implantation selection criteria, the incidence of reported second- or third-degree atrioventricular block varied between 0.4 and 1.8% per annum. Medical practice, however, has shifted to predominant implantation of DDD/R pacemakers in more than 95% of patients with sick sinus syndrome. Recent publications have reported an increase in left atrial diameter, decrease in left ventricular fractional shortening and increased incidence of atrial fibrillation in patients with DDD/R pacing as compared with patients with single chamber atrial devices. These changes were proportional to the percentage of ventricular paced beats. New algorithms in dual chamber devices have been developed in order to minimise ventricular stimulation. These are being evaluated at present. In my opinion there is still a place for atrial pacing in selected patients with sick sinus syndrome with a minimum risk of developing complete atrioventricular block. (Neth Heart J 2008;16(suppl 1): S25-S27.)     

Permanent cardiac pacing for neurocardiogenic syncope

Vasovagal syncope is not a benign condition in the elderly population. In patients not responsive to conservative therapy and whose abrupt faints are associated with serious injuries and seriously affected quality of life, pacemaker therapy was suggested. However, the usefulness of cardiac pacing for the prevention of recurrences of vasovagal syncope remains controversial because of the dominant role of the vasodepressor component during the episode. In the Medical Center Alkmaar, the Head-Up Tilt Test (HUTT) has been used since 1996 during the work-up of patients who present with vasovagal syncope. The HUTT showed a dominant cardioinhibitory response in 4.5% of our patients; in elderly patients with vasovagal syncope without prodromal symptoms and refractory on conservative therapy, pacemaker therapy was very effective in preventing syncope during long-term follow-up. (Neth Heart J 2008;16(suppl 1):S15-S19.)     

Dual-demand pacing for reciprocating atrioventricular tachycardia.

By using programmed electrical stimulation of the heart and studying the initiation and termination of reciprocating atrioventricular tachycardia two patients with the Wolff-Parkinson-White syndrome were shown to respond rapidly and consistently to fixed-rate pacing. A demand pacemaker was implanted in each patient, having been modified so as to switch into the fixed-rate mode whenever the tachycardia began, thereby terminating the arrhythmia. This appears to be a promising form of treatment in patients with otherwise intractable paroxysmal tachycardia who have been shown by careful study to respond in this way.     

Impaired sinus node function and global atrial conduction time after high rate atrial pacing in dogs

In animal and human studies, it has been shown that atrial fibrillation shortens the atrial refractory period and impairs its rate adaptation. The objective of this study was to evaluate the effects of high-rate pacing on sinus node function and intra-atrial conduction. Eight dogs were subjected to rapid atrial pacing (AP) at 400 bpm for 16 days. Sinus node recovery time (SNRT) and P-wave duration were measured at baseline, immediately after AP and four weeks after the termination of AP. SNRT immediately after AP was significantly prolonged at all pacing rates compared to the baseline values. P-wave duration was significantly longer after AP relative to the baseline values. All the variables were completely reversible four weeks after the termination of pacing. Rapid AP induces sinus node dysfunction and prolongs the intra-atrial conduction time. It is possible that the electrical remodelling extends to the sinus node as well.     

Computational method for discovery of estrogen responsive genes

Estrogen has a profound impact on human physiology and affects numerous genes. The classical estrogen reaction is mediated by its receptors (ERs), which bind to the estrogen response elements (EREs) in target gene's promoter region. Due to tedious and expensive experiments, a limited number of human genes are functionally well characterized. It is still unclear how many and which human genes respond to estrogen treatment. We propose a simple, economic, yet effective computational method to predict a subclass of estrogen responsive genes. Our method relies on the similarity of ERE frames across different promoters in the human genome. Matching ERE frames of a test set of 60 known estrogen responsive genes to the collection of over 18,000 human promoters, we obtained 604 candidate genes. Evaluating our result by comparison with the published microarray data and literature, we found that more than half (53.6%, 324/604) of predicted candidate genes are responsive to estrogen. We believe this method can significantly reduce the number of testing potential estrogen target genes and provide functional clues for annotating part of genes that lack functional information.     

Permanent parahisian pacing

Right Ventricular Apical permanent pacing could have negative hemodynamic effects. A physiologic pacing modality should preserve a correct atrio-ventricular and interventricular synchronization. This can be obtained through biventricular pacing, left ventricular pacing, or from alternative right ventricular pacing sites. Direct His Bundle Pacing (DHBP) was documented as reliable and effective for preventing the desynchronization and negative effects of right ventricular apical pacing. It is, however, a complex method that requires longer average implant times, cannot be carried out on all patients and presents high pacing thresholds. On the contrary, the parahisian pacing, with simpler feasibility and reliability criteria, seems to guarantee an early invasion of the His-Purkinje conduction system, with a physiological ventricular activation, very similar to the one that can be obtained with direct His bundle pacing. We present our experience on 68 patients who underwent a permanent right ventricular pacing in hisian/parahisian region, for advanced AV block and narrow QRS. In the first 17 patients we performed a double-blind randomized controlled study, with two 6-months cross-over periods in parahisian and apical pacing, documenting a significant improvement of NYHA class, exercise tolerance, quality of life score, mitral and tricuspidal regurgitation degree, and interventricular mechanical delay. In the subsequent 51 patients, in a mean follow of 21 months/patient, the pacing threshold remained stable (0.7+/-0.5 V implant; 0.9+/-0.7 V follow-up; p=0.08). The ejection fraction maintained medium-long term stable values, confirming the fact that the parahisian pacing can prevent deterioration of the left ventricular function. Parahisian pacing, therefore, has proven to be a reliable method, easy to apply and effective in preventing the negative effects induced by non-physiological right ventricular apical pacing.     

Permanent demand pacing for hypersensitive carotid sinus syndrome

Ten patients with proved hypersensitivity of one or both carotid sinuses and with symptoms of recurrent lightheaded spells and syncope had implanted a permanent transvenous demand pacemaker. In a follow-up course ranging from 6 to 55 months there has been no recurrence of lightheadedness or syncope in any of the patients. Six of the ten have had their battery packs replaced owing to routine battery exhaustion.     

Atrial pacing for rhythm control of atrial fibrillation

After atrial fibrillation (AF) develops, the first step is to search for and treat underlying (heart) s. Thereafter, AF should be treated. This includes prevention of cardiovascular morbidity and mortality, especially vascular events, and reduction of symptoms.1 The latter may be obtained by two treatment strategies: rhythm-control and/or rate-control treatment. Recent randomised trials have shown that rate control is not inferior to rhythm control with regard to cardiovascular morbidity and mortality.2 In these studies, predominantly elderly patients with underlying heart s (especially hypertension) were included. Patients with (severely) symptomatic AF and advanced heart failure were excluded. Since then, rate-control treatment has been adopted more frequently, even as first-choice therapy, especially in the elderly.