DDDR versus DDD and VVIR pacing: A single blind randomised evaluation of symptoms and effort performance

The aim of this study was to evaluate effort performance and subjective symptoms in a within-patient comparison of DDDR, DDD and VVIR pacing. A DDDR pacemaker (Synergyst II, Medtronic) was implanted in 14 patients (mean age 66.5 ± 5.0 yrs.) with sick sinus syndrome or II-III degree AV block. Seven subjects had chronotropic incompetence (maximum heart rate on exercise < 100 beats/min or maximum heart rate after i.v. atropine < 100 beats/min). All the patients underwent a symptom limited exercise test and a questionnaire score after 1 month of DDDR, DDD and VVIR pacing, in random order. The mean effort duration in DDDR was 12.6 ± 3.1 min, in VVIR 11.4 ± 3.4 min (p < 0.01 vs DDDR) and in DDD = 11.0 ± 2.9 min (p < 0.01 vs DDDR). Considering the subgroup of patients with chronotropic incompetence the same differences persisted whilst in the 6 subjects without chronotropic incompetence who completed the study DDDR pacing was statistically superior only to DDD and not to VVIR pacing. VVIR pacing was poorly tolerated since in all the groups of patients its symptom score was significantly higher compared with either DDDR or DDD pacing. In conclusion DDDR pacing is characterised by a superior maximal effort capacity in comparison with DDD pacing and VVIR pacing. In patients with chronotropic incompetence these differences are more marked. Moreover VVIR pacing appears poorly tolerated in subjective terms and in occurrence of side effects

Acute corticosterone sexually dimorphically facilitates social learning and inhibits feeding in mice

In numerous species social learning is predominant and adaptive, yet, we know little of its neurobiological mechanisms. Social learning is modulated by motivations and emotions, in a manner that is often sexually dimorphic. Additionally, stress hormones acutely modulate the related social cognitive process of social recognition. Whether this is true even for social learning is currently unknown.We investigated the acute effects of the stress hormone corticosterone (CORT) on the social transmission of food preferences (STFP) in male and female mice. During a brief social interaction an observer (OBS) acquires a food preference from a same-sex demonstrator (DEM). CORT (1.0, 2.5, 5.0 mg/kg), its ethanol vehicle (0.1%), and saline solution (0.9%) were administered intraperitoneally to the OBS, 10 min before a 30-min social interaction. Levels of plasma CORT were assessed in other mice that had received the same doses of CORT and either had or had not gone through a 30 min social interaction 10 min post-treatment. Exogenous CORT elicited levels of plasma level comparable to those seen at the peak of the circadian cycle and facilitated the STFP with males responding more than females both in terms of the duration of the food preference and the minimum effective dose. CORT also sexually dimorphically inhibited feeding, with females showing a greater doseeresponse than males. Saline solution and ethanol vehicles also sexually dimorphically facilitated the STFP and reduced feeding, but less than CORT did. These results indicate that CORT facilitates social learning, like social recognition. Hence, CORT may generally increase social information processing

Variability of Left Ventricular Electromechanical Activation during Right Ventricular Pacing: Implications for the Selection of the Optimal Pacing Site

BACKGROUND: The right ventricular septum (RVS) and Hisian area (HA) are considered more "physiological" pacing sites than right ventricular apex (RVA). Studies comparing RVS to RVA sites have produced controversial results. There are no data about variability of electromechanical activation obtained by an approach using fluoroscopy and electrophysiological markers. This study compared the variability of left ventricular (LV) electromechanical activation in patients undergoing short-term RVA and RVS with that measured during HA pacing based on fluoroscopy and electrophysiological markers. METHODS: Tissue Doppler echocardiography was performed in 142 patients before and after RVA (54), RVS (44), and HA (44) pacing. Electromechanical activation was assessed by: (1) electromechanical latency (EML)-interval between QRS onset and mechanical activation of basal LV; (2) intra-LV dyssynchrony (intra-LV)-interval between earliest to the latest LV basal motion. The intra- and interpatients variability among pacing groups were assessed. RESULTS: Pacing from RVA showed longer EML and higher degree of intra-LV than RVS and HA pacing. RVA and RVS showed a higher variability than HA pacing with regard to intrapatient changes of EML (RVA vs RVS, P = 0.4; RVS vs HA, P = 0.01, RVA vs HA, P = 0.0002) and intra-LV (RVA vs RVS, P = 0.2; RVS vs HA, P = 0.04; RVA vs HA, P = 0.005). Similar results were found in interpatients variability from paced-values. CONCLUSIONS: RVA and RVS pacing produce a variable effect on LV electromechanical activation that is significantly more pronounced than HA pacing. A pacing site such as HA selected by fluoroscopic and electrophysiological markers maintains baseline and homogeneous LV activation patter

Left Ventricular Dyssynchrony Resulting from Right Ventricular Apical Pacing: Relevance of Baseline Assessment

OBJECTIVES: Evaluation of left ventricular (LV) dyssynchrony in patients undergoing short-term right ventricular apical (RVA) pacing and correlation with baseline echocardiographic and clinical characteristics. BACKGROUND: RVA pacing causes abnormal ventricular depolarization that may lead to mechanical LV dyssynchrony. The relationships between pacing-induced LV dyssynchrony and baseline echocardiographic and clinical variables have not been fully clarified. METHODS: Tissue Doppler echocardiography was performed in 153 patients before and after RVA pacing. LV dyssynchrony was measured by the time between the shortest and longest electromechanical delays in the five basal LV segments (intra-LV). The prevalence and degree of LV dyssynchrony after RVA pacing was evaluated in three groups: baseline LV ejection fraction (LVEF) or=55%. The intrapatient effect of RVA pacing was determined as the percent increase in intra-LV value (Deltaintra-LV%). The pacing-induced intra-LV was correlated with baseline variables. RESULTS: The prevalence and degree of LV dyssynchrony after RVA pacing was significantly higher in patients with lower LVEF (P < 0.001). DeltaIntra-LV% was inversely correlated with baseline intra-LV and LVEF (B =-2.6, B =-4.2, P < 0.001). Baseline intra-LV and LV end-systolic volume correlated positively with intra-LV after RVA pacing (B = 0.49, B = 0.6, P < 0.001), whereas LVEF showed an inverse correlation. CONCLUSIONS: The degree of LV dyssynchrony induced by RVA is variable. Patients with higher baseline LV dyssynchrony, more dilated LV, and more depressed LVEF showed a higher degree of LV dyssynchrony during pacing. These findings may assume importance in predicting the risk of heart failure in pacemaker patients

Pharmacokinetics and hematologic response to subcutaneous administration of recombinant human erythropoietin in children undergoing long-term peritoneal dialysis: A multicenter study

For a study of the pharmacokinetics and hematologic response of subcutaneously administered recombinant human erythropoietin (rHuEPO), 24 children (mean age, 10 years 3 months; range, 3 months to 18 years) maintained by peritoneal dialysis and with anemia caused by end-stage renal failure (mean hemoglobin level, 6.5 gm/dl; range, 4.7 to 7.9) were treated with rHuEPO administered subcutaneously at an initial dose of 25 IU/kg twice per week. After a 4-week interval, in the case of no response (hemoglobin increase 641 to 1.5 gm/dl per month) the rHuEPO dosage was increased every 4 weeks according to the following schedule: 50, 75, 100, and 150 IU/kg twice per week. The administration of rHuEPO produced a rapid increase in serum concentration with a mean peak level of 59.8 mU/ml after 9 hours. Mean area under the curve to 72 hours was 2020 mU/ml per hour (range, 568 to 6609); mean elimination half-life and mean residence time were, respectively, 25.2 hours (range, 6.2 to 58.7) and 42.0 hours (range, 10.9 to 96). Of 24 children entered in the study, six had the drug suspended early because of renal transplantation (n = 1), lack of compliance (n = 4), or severe worsening of hypertension (n = 1). Eighteen patients had increased hemoglobin levels (to 9.4 \ub1 1.7 gm/dl after 24 weeks of treatment). No correlation was found between the increase in hemoglobin concentration and any of the pharmacokinetic data or the peak erythropoietin level reached during the kinetic profile. Eight children required an increase of antihypertensive medications to maintain satisfactory blood pressure values. We conclude that low doses of subcutaneously administered rHuEPO slowly release the drug into the blood and satisfactorily increase hemoglobin levels with very few side effects