The effect of per os colchicine administration in combination with fenofibrate and N-acetylcysteine on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease promoted by pro-inflammatory cytokines produced by NOD-, LRR- and pyrin domain-containing protein 3 (NLRP 3) inflammasome. Colchicine is an anti-inflammatory agent that inhibits inflammasome's action and stabilizes atherosclerotic lesions. N-acetylcysteine (NAC) reduces low-density lipoprotein (LDL) oxidation, metalloproteinase levels, and foam cell count and volume. Fenofibrate also has antioxidant, anti-inflammatory, and anticoagulant properties while also having a beneficial effect on the vasomotor function of the endothelium. The purpose of this study is to investigate the effect of per os colchicine administration in combination with fenofibrate and NAC on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits. MATERIALS AND METHODS: Twenty-eight male, 2 months old New Zealand White rabbits were separated into four groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w, cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 250 mg/kg body weight/day fenofibrate, and cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 15 mg/kg body weight/day NAC. Blood samples were drawn from all animals. Lipid profiles were assessed, and interleukin 6 (IL-6) measurements were performed using an enzyme-linked immunosorbent assay (ELISA) kit. Histologic examination was performed on aorta specimens stained with eosin and hematoxylin. Aortic intimal thickness was evaluated using image analysis. RESULTS: Colchicine administration in combination with fenofibrate or NAC statistically significantly reduced the extent of atherosclerotic lesions in aortic preparations. Co-administration of colchicine with NAC has a stronger anti-atherogenic effect than the colchicine plus fenofibrate regimen. Triglerycide levels were decreased in the colchicine plus fenofibrate group and the colchicine plus NAC group at the end of the experiment (p < 0.05), whereas the Cholesterol group had increased levels. A favorable significant lower concentration of IL-6 was detected in the colchicine plus NAC group vs. the other groups. CONCLUSIONS: In an experimental rabbit model, it appears that colchicine statistically significantly reduces the development of atherosclerosis of the aorta, especially in combination with NAC. Colchicine, as an NLRP3 inflammasome inhibitor, and NAC, as an agent that directly targets IL-6 signaling, can reduce the inflammatory risk. Fenofibrate enhances the attenuating role of colchicine on triglyceride levels. Clinical studies should investigate whether similar effects can be observed in humans.

Cryoablation for atrial fibrillation and antiarrhythmic drug pretreatment: a single referral center experience.

OBJECTIVE: Pulmonary vein isolation (PVI) ablation has emerged as the gold standard of ablative strategies to treat medically refractory paroxysmal and persistent atrial fibrillation (AF). Regardless of the superiority of catheter ablation based on PVI over antiarrhythmic drug therapy, recurrence rates of AF remain higher than desired. PVI via cryoablation has rapidly become a mainstream treatment for AF, due to its effectiveness and fast learning curve. Our objective was to assess the safety and efficacy of cryoablation in a single referral center. PATIENTS AND METHODS: This is a retrospective analysis of results after cryoablation treatment of AF over three years. 146 patients with AF underwent a cryoablation procedure in our clinical center and were followed-up for three years after the procedure. All patients received cryoablation of the pulmonary veins, although concomitant procedures were performed in 6 patients (re-ablation), including radiofrequency and cryoablation. RESULTS: Cryoablation was clinically successful in 90.83% of the patients with paroxysmal AF and 60% of those with persistent AF. The clinical success of cryoablation was correlated with pretreatment with amiodarone and in the case of re-ablation. Concerning postoperative complications, major bleeding was correlated with female gender, treatment with rivaroxaban and amiodarone. CONCLUSIONS: Among large trials, freedom from recurrent AF is about 65% with follow-up limited to 1 to 2 years. PVI via balloon cryoablation is a safe and efficient guideline-based treatment for AF, producing a durable event-free result in most patients out to 3 years with better outcomes than previously reported.