Conventional single-chamber pacemakers versus transcatheter pacing systems in a “real world” cohort of patients: A comparative prospective single-center study

PurposeDespite the developments in conventional transvenous pacemakers (VVI-PM), the procedure is still associated with significant complications. Although there are no prospective clinical trials that compared VVI-PM with transcatheter pacemaker systems (TPS).MethodsThis is a prospective, observational, single-center study that included all patients with an indication for a single-chamber pacemaker implant within a 4-year period. All clinical, ECG and echocardiographic characteristics at implant, electrical parameters, associated complications and mortality were analyzed. A Cox survival model and a Bayesian cohort analysis were performed for differences in complication rates between groups.ResultsThere were 443 patients included (198 TPS and 245 VVI-PM). The mean age was 81.5 years (TPS group, 79.2 ± 6.6 years; VVI-PM group, 83.5 ± 8.9 years). There was a male predominance in TPS group (123, 62.1% vs. 67, 27.3%; p < 0.001). The presence of systolic dysfunction and renal insufficiency were more frequent in VVI-PM group than in TPS patients. Mean follow-up was 22.3 ± 15.9 months. In a multivariable paired data the TPS group presented fewer complications than VVI-PM group (HR = 0.39 [0.15–0.98], p-value 0.013), but major complications were not different (6, 3% vs 14, 5.6% respectively, p = 0.1761). There was no difference in the mortality rate between the groups. The TPS group had less risk than VVI-PM group to have a complication, with a 96% of probability.ConclusionsTPS patients had a lower overall complication rate than VVI-PM patients including matched-pair samples using a Bayesian analysis. These results confirm the safety profile of TPS in clinical practice.     

Growth hormone secretagogues: the clinical future

Growth hormone (GH) releasing hexapeptide (GHRP)-6 and other peptidergic and non-peptidergic compounds collectively designated GH secretagogues (GHS) are potent releasers of GH in man. Their clinical future may be envisioned in three areas: therapy of GH-deficient (GHD) states, diagnosis of GHD, and non-endocrinological actions. As therapeutic agents and compared with GH itself, GHS have the disadvantage of lower potency but have a more physiological and safer profile of GH secretion. GHS administration could be indicated for states in which medium GH doses have been shown to be effective. As a diagnostic tool, the combined administration of GH releasing hormone plus GHRP-6, both at saturating doses, is currently the most powerful releaser of GH, devoid of side effects and convenient for the patient; it may also be an alternative to the insulin tolerance test for the diagnosis of GHD in adult patients. Their potential action at cardiovascular level is highly promising. Although the clinical future of GH releasing substances is appealing, probably the most relevant contribution has yet to be discovered. Once the endogenous ligand of the GHS receptor is identified, we will have an insight into the real hypothalamic control of GH secretion in man. With this knowledge it is likely that some diagnostic and therapeutic actions that are commonly undertaken will significantly change.     

Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation

Botulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real-time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano-high-performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha-defensin 3 (inflammation-involved protein) of patients who underwent open heart surgery ( n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml; p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.     

Oleic Acid Blocks Epidermal Growth Factor-Activated Early Intracellular Signals without Altering the Ensuing Mitogenic Response

In EGFR-T17 cells, which express high levels of the epidermal growth factor (EGF) receptor, addition of a saturating dose of EGF (10 nM) leads to an increase in Ins(1,4,5)P₃/diacylglycerol and also to cytosolic calcium [Ca²⁺]_i due to both intracellular redistribution and influx from extracellular medium. Pretreatment of cells with cis -unsaturated nonesterified fatty acids such as oleic acid (1 to 100 μM) inhibited EGF-stimulated Ins(1,4,5)P₃ generation and Ca²⁺ release from intracellular stores. Furthermore, such a treatment completely suppress Ca²⁺ influx in a dose-dependent manner. At doses capable of suppressing such early signals, oleic acid did not alter the process of EGF-mediated internalization of the EGF/EGF-receptor complex, suggesting that [Ca²⁺]_i rise did not mediate receptor internalization. EGF-induced cell proliferation assessed by either thymidine incorporation into DNA, direct cell counting, and microscopic observation was not altered by oleic acid, at doses able to block EGF-mediated early signals. In conclusion, suppression of Ins(1,4,5)P₃ generation and [Ca²⁺]_i rises by oleic acid did not alter EGF-receptor internalization nor EGF-induced cell mitosis. Such results suggest that [Ca²⁺]_i rise is not instrumental for EGF-stimulated cell proliferation.     

Dual effect of insulin on in vitro leptin secretion by adipose tissue

Although it is widely accepted that insulin stimulates leptin secretion, a dual action was observed using a validated in vitro system, i.e., an early (less than 48 h) inhibitory action, followed later (48-96 h) by a clear-cut stimulation. While the inhibitory phase was observed at every glucose concentration tested (from 1 to 25 mM), the stimulatory phase required the presence of physiological or supraphysiological glucose concentrations. In fact, leptin secretion was virtually eliminated in the presence of glucose uptake inhibitors. This dual effect of insulin was not due to modifications of the ob mRNA levels, suggesting that it depends entirely on posttranslational mechanisms. In conclusion, insulin appears to induce an early inhibition of leptin secretion by the adipose cell, followed later by a stimulatory effect secondary to the metabolic changes triggered by the insulin-induced increase in glucose uptake.     

Inositol 1,4,5-trisphosphate-independent Ca(2+) mobilization triggered by a lipid factor isolated from vitreous body.

A complex phospholipid from bovine vitreous body with a strong Ca(2+)-mobilizing activity has been recently isolated to homogeneity by our group. In this work, a sequential analysis of its transmembrane signaling pathway has been undertaken to characterize the intracellular mechanisms responsible for the Ca(2+) rise. The results show that this phospholipid induces, in a dose-dependent manner (ED(50) of around 0.25 microgram/ml), a Ca(2+) mobilization from inositol 1,4,5-trisphosphate-insensitive intracellular stores, with no participation of extracellular Ca(2+). Upon repeated administration, it shows no signs of autologous desensitization, does not induce heterologous desensitization of the L-alpha-lysophosphatidic acid (LPA) receptor but is desensitized by the previous administration of LPA. The Ca(2+)-mobilizing activity requires a membrane protein, is blocked after preincubation of the cells with pertussis toxin and phorbol esters, as well as by U73122 (an inhibitor of phospholipases C/D), R59022 (a diacylglycerol kinase inhibitor), and D609 (which inhibits phosphatidylcholine-specific phospholipase C). Upon administration of this phospholipid, the intracellular levels of phosphatidic acid (PA) rise with a time course that parallels that of the Ca(2+) mobilization, suggesting that PA could be responsible for this Ca(2+) signal. Exposure to AACOCF(3) (a specific inhibitor of phospholipase A(2)) does not modify the Ca(2+) rise, ruling out the possibility that the PA generated could be further converted to LPA by the action of phospholipase A(2). Based on the experimental data obtained, a signaling pathway involving a phosphatidylcholine-specific phospholipase C coupled to diacylglycerol kinase is proposed. This compound may represent a new class of bioactive lipids with a putative role in the physiology of the vitreous body.     

Seasonal changes in plasma leptin concentration related to antler cycle in Iberian red deer stags

The aim of this study is to describe the leptin cycle in male Iberian red deer (Cervus elaphus hispanicus) and relate it to antler and testosterone cycles. An additional aim is to assess the relationship between the plasma leptin concentration during antlers’ growth and their final size. Therefore, blood from 21 Iberian red deer males was sampled monthly to analyse leptin and testosterone. At the same time the deer were weighed and their body condition was assessed. The length of antlers was measured every 2 weeks and, after casting, their final length and perimeters were taken. Leptin showed a seasonal cycle, with a peak in June that decreased as testosterone increased. Low values were observed in autumn, winter and early spring. The relationship observed between leptin and body mass or body condition score was different in spring, when plasma testosterone concentration is low, than in autumn, when testosterone increases. Leptin peak amplitude was positively related to final antler size. In conclusion, the relationship between leptin and body mass and body condition score changes through the year, possibly due to the influence of androgens and photoperiod. There was a positive relationship between plasma concentration of leptin during antler growth and final antler length.