Different Effects of Palmitoyl-L-carnitine and Palmitoyl-CoA on Mitochondrial Function in Rat Ventricular Myocytes

Although mitochondrial oxidative catabolism of fatty acid (FA) is a major energy source for the adult mammalian heart, cardiac lipotoxity resulting from elevated serum FA and enhanced FA use has been implicated in the pathogenesis of heart failure. To investigate the effects of the intermediates of FA metabolism, palmitoyl-L-carnitine (Pal-car) and palmitoyl-CoA (Pal-CoA), on mitochondrial function, we measured membrane potential(Δψm), opening of the mitochondrial permeability transition pore (mPTP) and the production of reactive oxygen species (ROS) in saponin-treated rat ventricular myocytes with a laser scanning confocal microscope. Our results revealed that: 1) lower concentrations of Pal-car (1 and 5μM) caused a slight hyperpolarization of Δψm (TMRE intensity increased to 115.5 ± 5.4 % and 110.7±1.6 % of the baseline, respectively. p<0.05) but did not open mPTP, 2) a higher concentration of Pal-car (10μM) depolarized Δψm (TMRE intensity decreased to 61.9 ± 12.2 % of the baseline, p<0.01) and opened mPTP (calcein intensity decreased to 70.7 ± 2.8% of the baseline, p<0.01), 3) Pal-CoA depolarized Δψm without opening mPTP, and 4) only the higher concentration of Pal-car (10μM) increased ROS generation (DCF intensity increased to 3.4 ± 0.3 fold of the baseline). We concluded that excessive exogenous intermediates of long chain saturated FA may disturb mitochondrial function in different ways between Pal-car and Pal-CoA. The distinct mechanisms of the deteriorating effects of long chain FA on mitochondrial function are important for our understanding of the development of cardiac diseases in systemic metabolic disorders.浜松医科大学学位論文　医博第517号(平成２０年１０月１７日

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

BackgroundCryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce.MethodsThe YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible.ResultsA total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months.ConclusionsThe incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article

Accidental Entrapment of Electrical Mapping Catheter by Chiari’s Network in Right Atrium during Catheter Ablation Procedure

A 78-year-old male was admitted to our hospital due to frequent palpitation. His electrocardiogram (ECG) presented regular narrow QRS tachycardia with 170 bpm, and catheter ablation was planned. During electroanatomical mapping of the right atrium (RA) with a multiloop mapping catheter, the catheter head was entrapped nearby the ostium of inferior vena cava. Rotation and traction of the catheter failed to detach the catheter head from the RA wall. Exfoliation of connective tissue twined around catheter tip by forceps, which were designed for endomyocardial biopsy, succeeded to retract and remove the catheter. Postprocedural echocardiography and pathologic examination proved the existence of Chiari’s network. The handling of complex catheters in the RA has a potential risk of entrapment with Chiari’s network