scholarly journals Antiarrhythmic Effect of Ranolazine in Combination with Selective NCX-Inhibition in an Experimental Model of Atrial Fibrillation

2020 ◽  
Vol 13 (10) ◽  
pp. 321
Author(s):  
Julian Wolfes ◽  
Christian Ellermann ◽  
Niklas Broer ◽  
Benjamin Rath ◽  
Kevin Willy ◽  
...  

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 µM ranolazine and 1 µM of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 µM ranolazine and 1 µM of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Wolfes ◽  
C Ellermann ◽  
N Broer ◽  
K Willy ◽  
B Rath ◽  
...  

Abstract Background Previous studies showed an antiarrhythmic effect of ranolazine in different clinical and experimental studies. The aim of this study was to investigate the effects of a combination of ranolazine with different selective NCX-inhibitors in an established experimental model of atrial fibrillation. Methods and results 18 hearts of New Zealand white rabbits were retrogradely perfused. Left and right atrial catheters were used to record monophasic action potentials. Hearts were paced at three different cycle lengths (350ms, 250ms, 150ms). Thereby, cycle-length dependent atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness (aPRR=aERP-aAPD90) were obtained. Vulnerability to AF was tested by a standardized protocol employing several trains of burst pacing. After generating baseline data, the hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) to increase occurrence of AF. Afterwards, the hearts were assigned to two groups and additionally perfused with a combination of 10 μM ranolazine and 1 μM of the selective NCX-inhibitor ORM-10103 (group 1: Rano-ORM) or 10 μM ranolazine and 1 μM of another NCX-inhibitor, SEA0400 (group 2: Rano-SEA). Infusion of ACh/Iso led to a shortening of aAPD90 (group 1/2: −27.2ms/−24.5ms p<0.05), aERP (−29.2ms/−35.6ms p<0.05), aPRR (−12.2ms/−13.7ms p=ns) and the occurrence of AF-Episodes was significantly increased (group 1: baseline 6 episodes to 34 episodes under ACh/Iso p<0.05, group 2: baseline 7 episodes to 26 episodes under ACh/Iso p<0.05). Additional perfusion with ranolazine and ORM-10103 did not alter aAPD90 (−0,47ms) while effective refractory periods (+21.4ms, p<0.05) and aPRR (+43ms, p<0.05) were significantly prolonged and AF episodes were effectively reduced to 15 episodes (p<0.05). In group 2, Rano-SEA led to a slight decrease in aAPD90 (−9.5ms) while aERP (+13.3ms, p<0.05) and aPRR (+19.8ms, p<0.05) were prolonged. The occurrence of AF episodes was reduced to 15 episodes (p=0.1). Conclusion To our knowledge this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Atrial repolarization was not significantly changed with either of the combinations. However, both combinations prolonged aERP and aPRR and thereby suppressed induction of AF. Combining novel cellular targets may therefore lead to new potentially interesting options for antiarrhythmic AF therapy that have to be tested in clinical studies. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Ellermann ◽  
H Koenemann ◽  
J Wolfes ◽  
L Eckardt ◽  
G Frommeyer

Abstract Background Many clinical studies suggest an impact of propofol on the occurrence of atrial arrhythmias. Purpose Since experimental data is sparse, purpose of this study was to investigate the influence of propofol on atrial electrophysiology and the vulnerability to atrial fibrillation in a sensitive whole-heart model of atrial fibrillation. Methods 11 hearts of New Zealand white rabbits were isolated and Langendorff-perfused. Two catheters were placed on both atria to record atrial monophasic action potentials. Hearts were stimulated at three different cycle lengths (350ms, 250ms, 150ms), thereby obtaining cycle-length dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). Atrial post-repolarization (aPRR) refractoriness was defined as the difference between aERP and aAPD90. To increase the occurrence of atrial fibrillation, hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) after obtaining baseline data. Vulnerability to atrial fibrillation was tested by a standardized protocol consisting of several trains of burst pacing. Results Acetylcholine/isoproterenol infusion reduced aAPD90 (−3ms), aERP (−16ms) and aPRR (−14ms). Additional treatment with propofol prolonged aAPD90 (+5ms), aERP (+24ms) and aPRR (+20ms). Under baseline conditions, 13 episodes of atrial fibrillation lasting longer than 1s occurred. Additional treatment with acetylcholine/isoproterenol provoked more episodes of atrial fibrillation (33 episodes, p<0.05). Infusion of propofol on top of acetylcholine/isoproterenol significantly suppressed atrial fibrillation (2 episodes, p<0.05). Conclusion In this study, propofol prolonged aAPD90 and significantly reduced the occurrence of atrial fibrillation. Prolongation of effective refractory periods and especially of post-repolarization refractoriness protects the atrial myocardium against premature excitation and thereby prevents arrhythmias.


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Xiao-yu Liu ◽  
Hai-feng Shi ◽  
Jie Zheng ◽  
Ku-lin Li ◽  
Xiao-xi Zhao ◽  
...  

Objective. The objective of this study was to investigate the impact of left atrial (LA) size for the ablation of atrial fibrillation (AF) using remote magnetic navigation (RMN). Methods. A total of 165 patients with AF who underwent catheter ablation using RMN were included. The patients were divided into two groups based on LA diameter. Eighty-three patients had small LA (diameter <40 mm; Group A), and 82 patients had a large LA (diameter ≥40 mm; Group B). Results. During mapping and ablation, X-ray time (37.0 (99.0) s vs. 12 (30.1) s, P<0.001) and X-ray dose (1.4 (2.7) gy·cm2 vs. 0.7 (2.1) gy·cm2, P=0.013) were significantly higher in Group A. No serious complications occurred in any of the patients. There was no statistical difference in the rate of first anatomical attempt of pulmonary vein isolation between the two groups (71.1% vs. 57.3%, P=0.065). However, compared with Group B, the rate of sinus rhythm was higher (77.1% vs. 58.5%, P<0.001) during the follow-up period. More patients in Group A required a sheath adjustment (47/83 vs. 21/82, P<0.001), presumably due to less magnets positioned outside of the sheath. In vitro experiments with the RMN catheter demonstrated that only one magnet exposed created the sheath affects which influenced the flexibility of the catheter. Conclusions. AF ablation using RMN is safe and effective in both small and large LA patients. Patients with small LA may pose a greater difficulty when using RMN which may be attributed to the fewer magnets beyond the sheath. As a result, the exposure of radiation was increased. This study found that having at least two magnets of the catheter positioned outside of the sheath can ensure an appropriate flexibility of the catheter.


2011 ◽  
Vol 20 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Fagner Luiz da Costa Freitas ◽  
Beatriz Lie Yamamoto ◽  
Wagner Luiz da Costa Freitas ◽  
Jose Jurandir Fagliari ◽  
Katyane de Sousa Almeida ◽  
...  

Hemograms and acute-phase proteins in adult male New Zealand White rabbits that had been experimentally infected orally with sporulated oocysts of Eimeria stiedai were evaluated over a 28-day period. Fifty animals were used, divided into two groups: group A infected with 1 × 10(4) sporulated oocysts of E. stiedai and group B inoculated with distilled water. On the seventh day after infection, the infected animals presented anemia and leukocytosis with neutrophilia and monocytosis. Protein fractionation by means of electrophoresis identified 19 acute-phase proteins with molecular weights ranging from 24 to 238 kD. Ceruloplasmin, transferrin and haptoglobin showed high levels on the seventh day after infection, with gradual increases in their concentrations until the end of the experimental period. Thus, from the data of the present study, E. stiedai is considered to be a pyogenic etiological agent for which the infection level can be monitored through the leukocyte count and serum concentrations of ceruloplasmin, transferrin and haptoglobin, and these can be recommended as complementary tests.


Author(s):  
Masaharu Masuda ◽  
Mitsutoshi Asai ◽  
Osamu Iida ◽  
Shin Okamoto ◽  
Takayuki Ishihara ◽  
...  

Introduction: The randomized controlled VOLCANO trial demonstrated comparable 1-year rhythm outcomes between patients with and without ablation targeting low-voltage areas (LVAs) in addition to pulmonary vein isolation among paroxysmal atrial fibrillation (AF) patients with LVAs. To compare long-term AF/atrial tachycardia (AT) recurrence rates and types of recurrent-atrial-tachyarrhythmia between treatment cohorts during a > 2-year follow-up period. Methods: An extended-follow-up study of 402 patients enrolled in the VOLCANO trial with paroxysmal AF, divided into 4 groups based on the results of voltage mapping: Group A, no LVA (n=336); group B, LVA ablation (n=30); group C, LVA presence without ablation (n=32); and group D, incomplete voltage map (n=4). Results: At 25 (23, 31) months after the initial ablation, AF/AT recurrence rates were 19% in group A, 57% in group B, 59% in group C, and 100% in group D. Recurrence rates were higher in patients with LVAs than those without (group A vs. B+C, p<0.0001), and were comparable between those with and without LVA ablation (group B vs. C, p=0.83). Among patients who underwent repeat ablation, ATs were more frequently observed in patients with LVAs (Group B+C, 50% vs. A, 14%, p<0.0001). In addition, LVA ablation increased the incidence of AT development (group B, 71% vs. C, 32%, p<0.0001), especially biatrial tachycardia (20% vs. 0%, p=0.01). Conclusion: Patients with LVAs demonstrated poor long-term rhythm outcomes irrespective of LVA ablation. ATs were frequently observed in patients with LVAs, and LVA ablation might exacerbate iatrogenic ATs.


2021 ◽  
Author(s):  
gan zhang ◽  
Xiaosong Chen ◽  
Xunsheng Cheng ◽  
Xiuwu Ma ◽  
Congcong Chen

Abstract Introduction: The experiment was undertaken to estimate the effect of BMSCs seeding in different scaffold incorporation with HBO on the repair of seawater immersed bone defect. And future compared n-HA/PLGA with β-TCP/PLGA as scaffold in treatment effect of seawater immersed bone defect.Methods: 60 New Zealand White rabbits with standard seawater defect in radius were randomly divided to group A (implant with nothing), group B (implanted with atuogenous bone), group C (implanted with n-HA/PLGA/BMSCs, and Group D ( implanted with β-TCP/PLGA/BMSCs). After implant, each rabbit receive HBO treatment at 2.4 ATA 100% oxygen for 120 minutes per day for 2 weeeks. Radiograph, histological and biomechanical examination were used to analyze osteogenesis.Result: X-ray analysis show that n-HA/PLGA/BMSCs and β-TCP/PLGA/BMSCs could accelerate the new bone formation, and the new bone formation in group C was lager than in group D or group A, and close to group B (P<0.05). After 12 weeks, in group A, defect without scaffold show a loose connect tissue filled in the areas. The medullary canal in group B was recanalizated. Defect in group C and D show a larger number of wove bone formation. The new wove bone formation in defect areas in group C was lager than D. The mechanical examination revealed ultimate strength at 12 weeks were group D>group C>group B>group A(P<0.05).Conclusion: Scaffold of n-HA/PLGA and β-TCP/PLGA incorporation with HBO and BMSCs were effective to treat seawater immersed bone defect, and n-HA/PLGA was more excellent than β-TCP/PLGA.


2017 ◽  
Vol 44 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Zhengyu Bao ◽  
Hongwu Chen ◽  
Bing Yang ◽  
Michael Shehata ◽  
Weizhu Ju ◽  
...  

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients. Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs 99 ± 8.7 vs 94.5 ± 9.1 s; P=0.02). Group A's PP intervals were longer during adenosine triphosphate testing before ablation (4.6 ± 2.3 vs 1.7 ± 0.6 vs 1.5 ± 1 s; P &lt;0.001) and after ablation (4.7 ± 2.5 vs 2.2 ± 1.4 vs 1.6 ± 0.8 s; P &lt;0.001), and group A had more complex electrograms (11.4% ± 5.4% vs 9.3% ± 1.6% vs 5.8% ± 1.6%; P &lt;0.001). Compared with group C, group A had significantly longer corrected sinus node recovery times at a 400-ms pacing cycle length after ablation, larger RA volumes (100.1 ± 23.1 vs 83 ± 22.1 mL; P=0.04), and lower conduction velocities in the high posterior (0.87 ± 0.13 vs 1.02 ± 0.21 mm/ms; P=0.02) and high lateral RA (0.89 ± 0.2 vs 1.1 ± 0.35 mm/ms; P=0.04). We found that patients with PSP upon termination of atrial fibrillation have RA electrophysiologic and electroanatomic abnormalities that warrant post-ablation monitoring.


Author(s):  
Noriyoshi Yashiki ◽  
Go Watanabe ◽  
Shigeyuki Tomita ◽  
Satoru Nishida ◽  
Tamotsu Yasuda ◽  
...  

Background In recent years, the invasiveness of coronary reconstruction has been markedly reduced. Awake off-pump coronary artery bypass (AOCAB), coronary bypass surgery with thoracic epidural anesthesia (TEA) without general anesthesia and cardiopulmonary bypass), has been reported in the literature. Because the details of this technique are still unclear, we evaluated its usefulness by examining the autonomic neural state and the incidence of arrhythmia. Methods Fifty-five patients who underwent elective coronary artery bypass grafting (CABG) between April and December 2003 were included in the study. Patients who underwent CABG under high TEA alone comprised group A, those who underwent CABG under general anesthesia combined with TEA comprised group B, and those who underwent CABG under general anesthesia alone comprised group C. Holter electrocardiography was performed before and after surgery, and perioperative electrocardiograms were recorded (before surgery and during surgery, postoperative days 0–3, and postoperative day 7). On obtained electrocardiograms, the autonomic neural state was evaluated by analysis of heart rate variability, and the incidence of atrial fibrillation. Results Concerning the autonomic neural state, sympathetic inhibition was observed during TEA in both groups A and B. After discontinuation of TEA, sympathetic activity recovered. Vagal activity was not inhibited in group A, but decreased during surgery and gradually recovered after surgery in group B. Evaluation of the balance between sympathetic and vagal activities showed that sympathetic activity became predominant rapidly on postoperative day 2 in group B but gradually after surgery in group A. The incidence of postoperative atrial fibrillation was the highest in group B. Conclusions In AOCAB, because there is no vagal inhibition, vagal dominance can be maintained after surgery. This may be associated with the lower incidence of postoperative atrial fibrillation in group A compared with group B. Further studies are necessary to evaluate the details of AOCAB.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nobuaki Tanaka ◽  
KOICHI INOUE ◽  
Atsushi Kobori ◽  
Kazuaki Kaitani ◽  
Takeshi Morimoto ◽  
...  

Background: Heart failure (HF) is the leading cause of death in patients with atrial fibrillation (AF). Radiofrequency catheter ablation (RFCA) of AF is effective for maintaining sinus rhythm though its impact on heart failure still remains controversial. Purpose: We sought to elucidate whether AF recurrence following RFCA was associated with subsequent HF hospitalizations. Methods: We conducted a large-scale, prospective, multicenter, observational study. A total of 4931 consecutive patients who underwent an initial RFCA for AF with longer than 1-year of follow-up in 26 centers were enrolled (average age, 64±10 years; non-paroxysmal AF, 35.7%). The median follow-up duration was 2.9 years. The primary endpoint was an HF hospitalization more than 1-year after the index RFCA. We compared the patients without AF recurrences (group A) to those with AF recurrences within 1-year post RFCA (group B). Results: The 1-year cumulative incidence of AF recurrences after a single procedure was 30.7% (group A=3418, group B=1513 patients). Group B had a lower body mass index (group A vs. group B,24.1±3.6 vs. 23.8±3.4 kg/m 2 , p=0.014), longer history of AF (1.9 vs. 3.1 years, p<0.0001), higher prevalence of non-paroxysmal AF (32.1% vs. 33.9%, p<0.0001), and valvular heart disease (5.9% vs. 7.8%, p=0.013). They also had a lower ejection fraction (63.7±9.4% vs. 62.8±9.6%, p=0.0043) and larger left atrial dimeter (39.7±6.6 vs. 40.6±7.0 mm, p<0.0001) on echocardiography. Hospitalizations for HF were observed in 57 patients (1.14%) more than 1-year after the RFCA and were significantly higher in group B than group A (group A vs. group B, 0.91% vs 1.72%, log-rank p=0.019). Conclusions: Among AF patients receiving RFCA, those with AF recurrences were at a greater risk of subsequent heart failure hospitalizations than those without AF recurrences. Recognition that AF recurrence following RFCA is a risk factor for a subsequent HF-related hospitalization is appropriate in clinical practice.


Folia Medica ◽  
2012 ◽  
Vol 54 (2) ◽  
pp. 27-31 ◽  
Author(s):  
Maria N. Negreva ◽  
Atanas P. Penev

ABSTRACT The incidence of atrial fibrillation has been rapidly increasing in recent years. The increased tonus of the sympathetic nervous system is related to the development of atrial fibrillation. OBJECTIVE: To study the effect of bisoprolol, a highly selective beta-blocker, on patients with recent-onset atrial fibrillation (< 48 hours) for regularization of the rhythm using propafenone. PATIENTS AND METHODS: The study includes 164 patients (81 women, 83 men, age 59.09 ± 10.81) with successfully restored sinus rhythm in recent-onset atrial fibrillation. The patients received either propafenone (group A, n = 82) or a combination of propafenone and bisoprolol (group B, n = 82). The studied patients were randomly allocated to the groups. Propafenone was administered intravenously as a 2 mg/kg bolus followed by infusion of 0.0078 mg/kg/min for 120 min and orally in dosage of 300 mg three times every 8 hours if arrhythmia persisted. Bisoprolol was administered in a single dose at the very beginning of propafenone treatment and only in patients from group B at a dose of 5 or 10 mg. Regularization of the rhythm was assessed at the 3rd, 6th, 12th and 24th hour. RESULTS: In the initial stages of regularization the combined therapy restored the sinus rhythm in a greater number of patients in comparison with the monotherapy (at the 6th hour 67.07% in group B versus 48.78% in group A, P < 0.05; at the 12th hour it was 87.80% versus 75.60%, respectively, P < 0.05). CONCLUSION: Early regularization of rhythm in patients with recent-onset atrial fibrillation reduces the likelihood of recurrent episodes of arrhythmia. This makes the application of selective beta-blockade clinically significant.


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