Home  About us  Contact
 

Pacemaker Current (pacemaker + current)

Distribution by Scientific Domains
Medical Sciences85%

Selected Abstracts

Does Bipolar Pacemaker Current Activate Blood Platelets?

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009
GRUNDE GJESDAL M.D.
Objective: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). Background: Both platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning to the pacemaker can. Methods: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. Results: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). Conclusions: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical relevance of these findings remains to be investigated. [source]

Endothelin-1 Modulates the Arrhythmogenic Activity of Pulmonary Veins

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2008
AMEYA R. UDYAVAR M.D.
Objective: Endothelin-1 has important cardiovascular effects and is activated during atrial fibrillation. Pulmonary veins (PVs) play a critical role in the pathophysiology of atrial fibrillation. The aim of this study was to evaluate whether endothelin-1 affects PV arrhythmogenic activity. Methods: Conventional microelectrodes were used to record the action potentials (APs) and contractility in isolated rabbit PV tissue specimens before and after the administration of endothelin-1 (0.1, 1, 10 nM). The ionic currents of isolated PV cardiomyocytes were investigated before and after the administration of endothelin-1 (10 nM) through whole-cell patch clamps. Results: In the tissue preparation, endothelin-1 (1, 10 nM) concentration dependently shortened the AP duration and decreased the PV firing rates. Endothelin-1 (10 nM) decreased the resting membrane potential. Endothelin-1 (0.1, 1, 10 nM) decreased the contractility and increased the resting diastolic tension. In single PV cardiomyocytes, endothelin-1 (10 nM) decreased the PV firing rates from 2.7 ± 1.0 Hz to 0.8 ± 0.5 Hz (n = 16). BQ-485 (100 ,M, endothelin-1 type A receptor blocker) reversed and prevented the chrono-inhibitory effects of endothelin-1 (10 nM). Endothelin-1 (10 nM) reduced the L-type calcium currents, transient outward currents, delayed rectifier currents, transient inward currents, and sodium,calcium exchanger currents in the PV cardiomyocytes with and without pacemaker activity. Endothelin-1 (10 nM) increased the inward rectifier potassium current, hyperpolarization-induced pacemaker current, and the sustained outward potassium current in PV cardiomyocytes with and without pacemaker activity. Conclusion: Endothelin-1 may have an antiarrhythmic potential through its direct electrophysiological effects on the PV cardiomyocytes and its action on multiple ionic currents. [source]

Sustained Inward Current and Pacemaker Activity of Mammalian Sinoatrial Node

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 8 2002
HENGGUI ZHANG Ph.D.
Sustained Inward Current in the Sinoatrial Node.Introduction: A novel sustained inward Na+ current ist, which sensitive to Ca2+ -antagonists and potentiated by beta-adrenergic stimulation, has been described in pacemaker cells of rabbit, guinea pig, and rat sinoatrial node, as well as rabbit AV node. Although ist has been suggested to be an important pacemaker current, this has never been tested experimentally because of the lack of a specific blocker. In this study, we address the role of ist in the pacemaker activity of the sinoatrial node cell using computer models. Methods and Results: The newly developed models of Zhang et al. for peripheral and central rabbit sinoatrial node cells and models of Noble and Noble, Demir et al., Wilders et al., and Dokos et al. for typical rabbit sinoatrial node cells were modified to incorporate equations for ist. The conductance gst was chosen to give a current density-voltage relationship consistent with experimental data. In the models of Zhang et al. (periphery), Noble and Noble, and Dokos et al., in which ist was smaller or about the same amplitude as other inward currents, ist increased the pacemaking rate by 0.6%, 2.2%, and 0.8%, respectively. In the models of Zhang et al. (center), Demir et al., and Wilders et al., in which ist was larger than some other inward ionic currents, ist increased the pacemaking rate by 7%, 20%, and 14%, respectively. Conclusion: ist has the potential to be a regulator of pacemaker activity, although its importance will depend on the amplitude of ist relative to the amplitude of other inward currents involved in pacemaker activity. [source]

Does Bipolar Pacemaker Current Activate Blood Platelets?

PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009
GRUNDE GJESDAL M.D.
Objective: The aim of this study was to investigate whether bipolar pacemaker current lead can activate blood platelets. The null hypothesis was that 1 minute of electrical stimulation of platelets would not influence their subsequent reactivity to adenosine diphosphate (ADP). Background: Both platelets and muscle cells contain actin and myosin filaments, and both cells are activated following calcium influx. Muscle cells open their calcium channels and contract when exposed to an electric current. Current through a bipolar pacemaker lead will expose a small volume of blood, including platelets, to the depolarizing current. Platelet activation may ensue, resulting in aggregation, release reaction, and contraction. In contrast, a unipolar pacemaker system will not depolarize blood, but transmit current directly into the myocardium, and the current afterward passes through other tissues before returning to the pacemaker can. Methods: Platelet-rich plasma was prepared from two healthy subjects. Platelet reactivity to the agonist ADP was tested in paired samples in an aggregometer in a case/control setup. Results: Eighteen of 46 tested pairs of platelet-rich plasma showed increased reactivity in the paced sample; 26 were unchanged while two showed decreased reactivity in the paced sample. Using a two-sided sign test, the null hypothesis was rejected (P = 0.0004). Conclusions: The study demonstrates increased reactivity to ADP in platelets exposed in vitro to stimulation by pacemaker current. The clinical relevance of these findings remains to be investigated. [source]

Engineering physiologically controlled pacemaker cells with lentiviral HCN4 gene transfer

THE JOURNAL OF GENE MEDICINE, Issue 5 2008
Gerard J. J. Boink
Abstract Background Research on biological pacemakers for the heart has so far mainly focused on short-term gene and cell therapies. To develop a clinically relevant biological pacemaker, long-term function and incorporation of autonomic modulation are crucial. Lentiviral vectors can mediate long-term gene expression, while isoform 4 of the Hyperpolarization-activated Cyclic Nucleotide-gated channel (encoded by HCN4) contributes to pacemaker function and responds maximally to cAMP, the second messenger in autonomic modulation. Material and Methods Action potential (AP) properties and pacemaker current (If) were studied in single neonatal rat ventricular myocytes that overexpressed HCN4 after lentiviral gene transduction. Autonomic responsiveness and cycle length stability were studied using extracellular electrograms of confluent cultured monolayers. Results Perforated patch-clamp experiments demonstrated that HCN4-transduced single cardiac myocytes exhibited a 10-fold higher If than non-transduced single myocytes, along with slow diastolic depolarization, comparable to pacemaker cells of the sinoatrial node, the dominant native pacemaker. HCN4-transduced monolayers exhibited a 47% increase in beating rate, compared to controls. Upon addition of DBcAMP, HCN4-transduced monolayers had beating rates which were 54% faster than baseline and significantly more regular than controls. Conclusions Lentiviral vectors efficiently transduce cardiac myocytes and mediate functional gene expression. Because HCN4-transduced myocytes demonstrate an increase in spontaneous beating rate and responsiveness to autonomic modulation, this approach may be useful to create a biological pacemaker. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestine

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2005
Jae Yeoul Jun
1We investigated the role of deoxycholic acid in pacemaker currents using whole-cell patch-clamp techniques at 30°C in cultured interstitial cells of Cajal (ICC) from murine small intestine. 2The treatment of ICC with deoxycholic acid resulted in a decrease in the frequency and amplitude of pacemaker currents and increases in resting outward currents. Also, under current clamping, deoxycholic acid produced the hyperpolarization of membrane potential and decreased the amplitude of the pacemaker potentials. 3These observed effects of deoxycholic acid on pacemaker currents and pacemaker potentials were completely suppressed by glibenclamide, an ATP-sensitive K+ channel blocker. 4NS-398, a specific cyclooxygenase-2 (COX-2) inhibitor, significantly inhibited the deoxycholic acid-induced effects. The treatment with prostaglandin E2 (PGE2) led to a decrease in the amplitude and frequency of pacemaker currents and to an increase in resting outward currents, and these observed effects of PGE2 were blocked by glibenclamide. 5We next examined the role of deoxycholic acid in the production of PGE2 in ICC, and found that deoxycholic acid increased PGE2 production through the induction of COX-2 enzyme activity and its gene expression. 6The results suggest that deoxycholic acid inhibits the pacemaker currents of ICC by activating ATP-sensitive K+ channels through the production of PGE2. British Journal of Pharmacology (2005) 144, 242,251. doi:10.1038/sj.bjp.0706074 [source]