Shorter AV Delays Provide Improved Echocardiographic Hemodynamics during Exercise in Patients Receiving Cardiac Resynchronization Therapy

Background: Although atrial ventricular (AV) intervals are often optimized at rest in patients receiving cardiac resynchronization therapy (CRT), there are limited data on the impact of exercise on optimal AV interval.
Methods: In 15 patients with CRT, AV intervals were serially programmed while patients were supine and at rest, and during exercise with heart rates that averaged 20 and 40 beats per minute above their resting rates. Echocardiographic Doppler images were acquired at each programmed AV interval and each rate. Three independent echocardiographic criteria were retrospectively used to determine each patient's optimal AV interval as a function of exercise-induced increased heart rates: the duration of left ventricular filling, stroke volume, and a clinical assessment of left ventricular function.
Results: A negative correlation between the optimal AV interval and heart rate was observed across all patients using all three independent criterion: the maximum left ventricular filling time (slope =–0.77, intercept = 151.9, r = 0.55, P < 0.001), maximum stroke volume (slope =–0.93, intercept = 183.3, r = 0.50, P = 0.002), or the subjective clinical assessment (slope =–1.06, intercept = 182.0, r = 0.72, P < 0.001). Consistent trends were observed between all three parameters for 12 out of the 15 patients.
Conclusions: These results suggest that in patients indicated for CRT, rate-adaptive functions may be useful to shorten AV intervals with increased rate, in order to maximize left ventricular filling, stroke volume, and clinical left ventricular function. Further studies are necessary to determine the clinical impact of these rate-adaptive algorithms.     

High Voltage Shock Induced Cellular Electrophysiological Effects: Transient Refractoriness and Bimodal Changes in Action Potential Duration

LI, H.G., et al .: High Voltage Shock Induced Cellular Electrophysiological Effects: Transient Refractoriness and Bimodal Changes in Action Potential Duration . The cellular electrophysiological effects of defibrillation shocks on the myocardium during ventricular fibrillation are not clear. The present study investigated the effects of high voltage shocks on membrane potentials of isolated guinea pig and pig papillary muscles during rapid activations simulating ventricular fibrillation. High voltage shocks induced an action potential with a prolonged duration, followed by a transient refractory state. Subsequent action potentials following this refractory state had shortened durations. The duration of the transient refractory state varied in proportion to shock intensity and stimulation rate, whether the shock was biphasic or monophasic. Shock induced prolonged depolarization was not a consistent finding and mainly observed with slow stimulation rates. In conclusion, high voltage shocks induce bimodal changes of the action potential duration associated with a transient refractory state during rapid activation. The rate dependency of this refractory state suggests that the duration of the shock induced refractory state may be longer in the fibrillating than the normal beating heart, and may contribute to successful defibrillation.     

Effects of Autonomic Manipulation on Ventricular Fibrillation and Internal Cardiac Defibrillation Thresholds in Pigs

Autonomic tone may contribute to cardiac arrhythmogenesis and influence the efficacy of implantable defibrillators. Fifty-two anesthetized pigs were randomized to: (1) methacholine (n = 12); (2) nitroprusside (n = 12); (3) phenylephrine (n = 12); (4) carbachol (n = 8); and (5) saline (n = 8). Ventricular fibrillation threshold (VFT) and triplicate defibrillation thresholds (DFT) were obtained before and during each intervention. Mean (± SE) VFT was increased with: methacholine (76 ± 10.6 V vs 39 ± 7.1 V, P < 0.001); phenylephrine (68 ± 10.5 V vs 38 ± 6.2 V, P < 0.001); and carbachol (106 ± 11.5 V vs 30 ± 6.5 V, P < 0.0001). Nitroprusside and saline failed to alter VFT. Mean (± SE) DFT was decreased with: methacholine (7.7 ± 0.8 J vs 9.7 ± 0.8 J, P < 0.001); phenylephrine (9.8 ± 0.9 J vs 11.3 ± 1.0 1, P < 0.05); and carbachol (9.2 ± 0.7 J vs 12.2 ± 0.8), P < 0.0001), remaining unchanged following nitroprusside and saline infusion. Thus, modulation of autonomic tone modified arrhythmia susceptibility and the energy necessary for defibrillation, increased parasympathetic tone, increased VFT, and decreased DFT. Evaluation of autonomic balance, particularly parasympathetic tone, may be useful with the implantation of automatic defibrillators.     

Gene therapy: Recent advances and applications in gastroenterology and hepatology

Abstract The advantages and disadvantages of viral and non-viral vectors for gene delivery are reviewed. Advances in systems for introduction of new gene expression are described, including self-deleting retroviral transfer vectors, chimeric viruses and chimeric oligonucleotides. Systems for inhibition of gene expression are also discussed including antisense oligonucleotides, ribozymes and dominant-negative genes. Examples of the use of these systems in animal models and clinical trials for gastrointestinal disorders are discussed.     

Bare Stent Implantation Through a Side Slot of Another Stent in a Bifurcation Lesion

A case of a patient with significant (≈ 90%) stenosis of the circumflex at its origin from the left main artery and of the first marginal branch, 20 mm after its origin from the circumflex, is described. The case was treated with implantation of two stents, one at the marginal and another at the circumflex through a side slot of the first stent.     

Unconditioned Stimulus Intensity and Retention Interval Effects

In single-element taste-aversion learning, retention interval effects are seen if taste aversions are paradoxically weak when they are tested 1 day after conditioning than when they are tested 3 or more days after conditioning. One explanation of this phenomenon is that weaker taste aversions may increase in strength across a retention interval. To test this possibility, rats were given saccharin followed by an unconditioned stimulus (US) of weak, medium, or high intensity; testing occurred after a 1-day or a 5-day retention interval. The results showed retention-interval effects only at medium and high dosage levels, but not following a weak-intensity US. Furthermore, at the 5-day retention interval, aversion strength increased as the intensity of the US increased. However, at the 1-day retention interval, there were no significant differences due to US intensity. In accordance with previous experiments, this outcome suggests that nonassociative factors, such as US novelty, and not associative factors (e.g., US intensity), modulate taste aversion performance on a 1-day test.     

Sigmoidorectal (Mainz II) pouch for continent urinary diversion in bladder cancer

BACKGROUND: We aimed to assess the feasibility, safety, and outcome of the sigmoidorectal (Mainz II) pouch for urinary diversion in patients with invasive bladder cancer. METHODS: Twenty-nine patients (25 men and four women), aged 65-76 years, who had undergone radical cystectomy and the sigmoidorectal pouch procedure for invasive bladder cancer were included in this study. Postoperative evaluations included metabolic testing, standard laboratory screening, renal ultrasonography, pouchography, and intravenous urography or pouchoscopy when indicated. RESULTS: The median operative time was 175 min. Urine leakage was encountered in two patients (6.8%), deep vein thrombosis in one (3.4%), and ileus necessitating surgery in another one. Two patients developed pyelonephritis due to ureterocolonic stricture, which was treated with antegrade balloon dilatation. No local relapses of bladder cancer were found. All patients were continent during the day, but one patient was occasionally incontinent during the night. In the long term, six patients (20.6%) developed metastatic disease, and five patients (17.2%) died because of cancer-related causes. Overall survival was 100, 96 and 60% at 1, 2 and 3 years after the operation, respectively. The mean survival was 36.8 +/- 1.9 months, which was statistically significantly associated with the M stage (P < 0.001), but not with the T (P = 0.091) or N (P = 0.081) stages. CONCLUSIONS: The sigmoidorectal (Mainz II) pouch seems to be a feasible, safe and effective method for continent urinary diversion. It is able to provide good quality of life, and ensure good overall survival rates.     

Isolation,identification, and characterization of a palladium complex in the catalytic deprotection of a protected peptide

The final catalytic deprotection in the large scale synthesis of thymopentin (Arg-Lys-Asp-Val-Tyr) produced an impurity which had not previously been observed. Isolation by preparative HPLC and spectroscopic characterization led to a postulated structure of the impurity as the 1: 1 thymopentin-palladium complex. A complex corresponding to the proposed structure was independently synthesized and shown to have identical chromatographic and spectroscopic properties with the isolated material. Proton and carbon (13) NMR were used to determine the coordination sites of the peptide with palladium. The susceptibility of the complex to hydrogenation indicated a possible source for its formation.     

The Effect of DDD Pacing on Ergospirometric Parameters and Neurohormonal Activity in Patients with Hypertrophic Obstructive Cardiomyopathy

This study examined the acute and long-term effects of DDD pacing on ergospirometric parameters and neurohormonal activity in patients with hypertrophic obstructive Cardiomyopathy (HOCM). We studied eight patients (five males), aged 56 ± 7 years, with HOCM refractory to drugs. In all patients a DDD pacemaker was implanted and programmed with an atrioventricular (AV) delay that insured full ventricular activation. The patients underwent echocardiographic examination and exercise stress testing before and 3 days, 3 months, and 12 months after pacemaker implantation. Oxygen consumption was measured at the anaerobic threshold (VO_2AT) and peak exercise (pVO₂). Atrial natriuretic peptide (ANP) and cyclic adenosine monophosphate (c-AMP) levels were measured concomitantly. Left ventricular outflow tract (LVOT) pressure gradient decreased significantly from 70 ± 18 to 25 ± 12 mmHg (P < 0.05) 3 days after pacing and remained unchanged at 3 and 12 months. pVO₂ and VO_2AT increased significantly, from 20.1 ± 3 to 23.4 ± 3 mL/kg/min and from 16 ± 3 to 17.8 ± 2 mL/kg/min, respectively (P < 0.05). This improvement continued up to 3 months, and then remained stable until the end of the 12-month follow-up period. ANP levels decreased at 3 days from 85.4 ± 5.7 to 75.4 ± 7.3 fmol/mL (P < 0.05), and remained unchanged over the 12 months. c-AMP levels did not change significantly after the onset of pacing. DDD pacing in patients with HOCM not only reduces the LVOT pressure gradient but also causes a significant early and long-term improvement in exercise capacity and neurohormonal profile.