Azithromycin acts as an immunomodulatory agent to suppress the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is highly expressed in inflammatory lesions caused by infectious agents such as bacteria and fungi but not in normal tissues or non-infectious lesions. There is evidence that macrolide antibiotics can act as immunomodulatory agents. The purpose of the current study was to determine whether azithromycin, a type of macrolide antibiotic, could reduce the expression of TREM-1 in Bacillus pyocyaneus-induced sepsis in vitro and in vivo. We treated THP-1 cells with LPS, LPS+TREM-1/Fc, and LPS+azithromycin for in vitro study. A B. pyocyaneus pyemia animal model was developed for in vivo study. RT-PCR, western blotting, and flow cytometry (FCM) were employed to determine the expression of TREM-1. ELISA analysis was utilized to examine the concentration of cytokines. Our results showed that azithromycin treatment did not reduce the level of LPS-induced TREM-1 mRNA in THP-1 cells. However, treatment with TREM-1/Fc fusion protein or azithromycin reduced the effect of LPS-stimulated TREM-1 protein expression. The expression of inflammatory factors (TNF-α, IL-6, and IL-1ß) in cell culture supernatant and mouse serum of the TREM-1/Fc fusion protein-treated and azithromycin-treated groups were lower than that of the control group (p<0.05). The results from the animal sepsis model experiments demonstrated that the TREM-1 Fc/fusion protein and azithromycin treatment groups' survival rates were significantly higher than in the control group. Analysis of serum inflammatory factors in septic mice revealed that the concentration of these factors was significantly lower than in the control group. Our results furthered the understanding of azithromycin function in immunological regulation and provided reliable data for new clinical applications.

Cryoablation versus radiofrequency energy for the ablation of atrioventricular nodal reentrant tachycardia (the CYRANO Study): results from a large multicenter prospective randomized trial.

BACKGROUND: Cryoablation has emerged as an alternative to radiofrequency catheter ablation (RFCA) for the treatment of atrioventricular (AV) nodal reentrant tachycardia (AVNRT). The purpose of this prospective randomized study was to test whether cryoablation is as effective as RFCA during both short-term and long-term follow-up with a lower risk of permanent AV block. METHODS AND RESULTS: A total of 509 patients underwent slow pathway cryoablation (n=251) or RFCA (n=258). The primary end point was immediate ablation failure, permanent AV block, and AVNRT recurrence during a 6-month follow-up. Secondary end points included procedural parameters, device functionality, and pain perception. Significantly more patients in the cryoablation group than the RFCA group reached the primary end point (12.6% versus 6.3%; P=0.018). Whereas immediate ablation success (96.8% versus 98.4%) and occurrence of permanent AV block (0% versus 0.4%) did not differ, AVNRT recurrence was significantly more frequent in the cryoablation group (9.4% versus 4.4%; P=0.029). In the cryoablation group, procedure duration was longer (138±54 versus 123±48 minutes; P=0.0012) and more device problems occurred (13 versus 2 patients; P=0.033). Pain perception was lower in the cryoablation group (P<0.001). CONCLUSIONS: Cryoablation for AVNRT is as effective as RFCA over the short term but is associated with a higher recurrence rate at the 6-month follow-up. The risk of permanent AV block does not differ significantly between cryoablation and RFCA. The potential benefits of cryoenergy relative to ablation safety and pain perception are counterbalanced by longer procedure times, more device problems, and a high recurrence rate. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00196222.

[Chronic effects on the prevention of atrial fibrillation recurrence in patients with lone paroxysmal atrial fibrillation treated with amiodarone, segmental pulmonary vein ablation, or amiodarone plus losartan: a prospective cohort study].

OBJECTIVE: This study was designed to compare clinical efficacy of segmental pulmonary vein ablation (SPVI), amiodarone or amiodarone plus losartan on sinus rhythm maintenance in patients with lone paroxysmal atrial fibrillation (PAF). METHODS: Patients with lone PAF were treated with amiodarone alone (A, n = 52), segmental pulmonary vein isolation (SPVI, n = 51), or amiodarone plus losartan (AL, n = 51). The primary endpoint of this study was the incidence of symptomatic atrial tachyarrhythmia (> 30 s) documented by 12 lead ECG or Holter during 12 months follow-up period. RESULTS: During follow-up, AF was documented in 24 patients (46.2%) in A group, 11 patients (21.6%) in SPVI group and 12 (23.5%) in AL group (P < 0.05 vs. A group). The Kaplan-Meier survival analysis demonstrated a significant equally reduction in AF recurrence in SPVI and AL groups (P = 0.009, log-rank test and P = 0.018, log-rank test, respectively) compared with A group. The hazard ratio for AF recurrence in patients treated with SPVI and amiodarone plus losartan was 0.41 (95% CI 0.200 to 0.848, P = 0.016) and 0.46 (95% CI 0.225 to 0.953, P = 0.036), respectively. Incidences of major adverse cardiac events were similar among the groups (9.6% in A, 3.9% in SPVI and 7.8% in AL group, P > 0.05). CONCLUSION: The results of this study suggest that the segmental pulmonary vein isolation and amiodarone plus losartan are superior to amiodarone alone for preventing AF recurrence in patients with lone PAF.

[Long-term clinical efficacy of losartan or perindopril combination therapy with low-dose amiodarone in patients with paroxysmal atrial fibrillation].

OBJECTIVE: The purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF). METHODS: One hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF. RESULTS: During the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3. CONCLUSIONS: The results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.