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Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

ABSTRACT: Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models.To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP).In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseline and after 15 minutes of SCS. Following recovery in a subset of canines, pacemakers were turned on to induce AF by alternately delivering TP and searching for AF. Canines were randomized to no SCS therapy (CTL) or intermittent SCS therapy on the initiation of TP (EARLY) or after 8 weeks of TP (LATE). AF burden (percent AF relative to total sense time) and AF inducibility (percentage of TP periods resulting in AF) were monitored weekly. After 15 weeks, echocardiography and histology were performed.Effective refractory periods increased by 21 ± 14 ms (P = .001) in the left atrium and 29 ± 12 ms (P = .002) in the right atrium after acute SCS. AF burden was reduced for 11 weeks in EARLY compared with CTL (P <.05) animals. AF inducibility remained lower by week 15 in EARLY compared with CTL animals (32% ± 10% vs 91% ± 6%; P <.05). AF burden and inducibility were not significantly different between LATE and CTL animals. There were no structural differences among any groups.SCS prolonged atrial effective refractory periods and reduced AF burden and inducibility in a canine AF model induced by TP. These data suggest that SCS may represent a treatment option for AF.

SUBMITTER: Bernstein SA

PROVIDER: S-EPMC3634125 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

Bernstein Scott A SA Wong Brian B Vasquez Carolina C Rosenberg Stuart P SP Rooke Ryan R Kuznekoff Laura M LM Lader Joshua M JM Mahoney Vanessa M VM Budylin Tatyana T Älvstrand Marie M Rakowski-Anderson Tammy T Bharmi Rupinder R Shah Riddhi R Fowler Steven S Holmes Douglas D Farazi Taraneh G TG Chinitz Larry A LA Morley Gregory E GE

Heart rhythm 20120501 9

<h4>Background</h4>Spinal cord stimulation (SCS) has been shown to modulate atrial electrophysiology and confer protection against ischemia and ventricular arrhythmias in animal models.<h4>Objective</h4>To determine whether SCS reduces the susceptibility to atrial fibrillation (AF) induced by tachypacing (TP).<h4>Methods</h4>In 21 canines, upper thoracic SCS systems and custom cardiac pacing systems were implanted. Right atrial and left atrial effective refractory periods were measured at baseli ...[more]

PMID: 22554859

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Project description:Atrial fibrillation (AF) is one of the most common types of arrhythmia worldwide; although a number of theories have been proposed to explain the mechanisms of AF, the treatment of AF is far from satisfactory. Energy metabolism is associated with the development of AF. Mitochondrial transcription factor A (TFAM) serves a role in the maintenance and transcription of mitochondrial DNA. The present study aimed to investigate the association between TFAM and AF and the effect of TFAM on ATP content in cardiomyocytes. Left atrial appendage tissues were collected from 20 patients with normal sinus rhythm (SR) and 20 patients with AF, and the expression levels of TFAM in SR and AF tissues were evaluated. In addition, a tachypacing model of primary cultured cardiomyocytes was constructed to assess ATP content, cell viability and expression levels of TFAM, mitochondrially encoded (MT)‑NADH dehydrogenase 1 (ND1), MT‑cytochrome c oxidase 1 (CO1), NADH ubiquinone oxidoreductase core subunit 1 (NDUFS1) and cytochrome c oxidase subunit 6C (COX6C). Finally, the effects of overexpression and inhibition of TFAM on ATP content, cell viability and the expression levels of MT‑ND1 and MT‑CO1 were investigated. The expression levels of TFAM were decreased in AF tissues compared with SR tissues (P<0.05). The ATP content, cell viability and expression levels of TFAM, MT‑ND1 and MT‑CO1 were decreased in tachypacing cardiomyocytes compared with non‑pacing cardiomyocytes (P<0.05), whereas the expression levels of NDUFS1 and COX6C were not changed (P>0.05). Overexpression of TFAM increased ATP content, cell viability and expression levels of MT‑ND1 and MT‑CO1 (P<0.05). The inhibition of TFAM decreased ATP content, cell viability and expression levels of MT‑ND1 and MT‑CO1 (P<0.05). In summary, the results of the present study demonstrated that the expression levels of TFAM were decreased in AF tissues and tachypacing cardiomyocytes and that the restoration of TFAM increased the ATP content by upregulating the expression levels of MT‑ND1 and MT‑CO1 in tachypacing cardiomyocytes. Thus, TFAM may be a novel beneficial target for treatment of patients with AF.

Project description:Background and purposeInhibition of the G-protein gated ACh-activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.Experimental approachThe pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.Key resultsXAF-1407 potently and selectively inhibited Kir 3.1/3.4 and Kir 3.4/3.4, underlying the IK,ACh current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.Conclusion and implicationsXAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

Project description:BackgroundThere is emerging evidence that astaxanthin plays a significant role in protecting neuro-cells from apoptosis after central nervous system injury. Our study examined the effects of astaxanthin on neuro-cell apoptosis after spinal cord injury.MethodsOne hundred and forty-four healthy adult Sprague-Dawley rats were randomly divided into the experimental group, control group, and sham operation group (n=48). Spinal cord injury was induced using the modified Allen method in the control group and the experimental group; while in the sham operation group, the lamina was removed without spinal cord injury. The rats in the experimental group were given astaxanthin (75 mg/kg) by gavage immediately after the operation, and in the other groups were given the same amount of olive oil. Motor function was assessed by blood-brain barrier (BBB) scores. The malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) at 24 h was determined after the operation. The apoptosis index (AI) was determined at 6, 24, and 48 h after the operation. At 48 h after the operation, we calculated the water content of the spinal cord, the lesion ratio of the spinal cord, the ultrastructure of the spinal cord, and the ultrastructure score.ResultsThe BBB scores of the control and experimental groups were significantly lower than the sham operation group at each postoperative time (P<0.05), and the BBB score of the experimental group was significantly higher than the control group at 1-4 weeks postoperatively (P<0.05). At 24 hours postoperatively, MDA content was highest in the control group and lowest in the sham operation group, while SOD activity was highest in the sham operation group and lowest in the control group (P<0.05). At each time point postoperatively, the sham operation group had the lowest AI and the control group had the highest AI (P<0.05). At 48 h after the operation, the water content and the lesion ratio of the spinal cord, and the ultrastructure score were the lowest in the sham operation group and the highest in the control group (P<0.05).ConclusionsAstaxanthin significantly improved the motor function of rats with spinal cord injury.

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Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

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Spinal cord stimulation protects against atrial fibrillation induced by tachypacing.

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