clinicaltrials.gov Identifier: NCT01327976.

VBLOC® therapy to treat morbid obesity was safe, but weight loss was not greater in treated compared to controls; clinically important weight loss, however, was related to hours of device use. Post-study analysis suggested that the system electrical safety checks (low charge delivered via the system for electrical impedance, safety, and diagnostic checks) may have contributed to weight loss in the control group.

Background. An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies. Objective. To prospectively evaluate the effect of intermittent vagal blocking (VBLOC) on weight loss, glycemic control, and blood pressure (BP) in obese subjects with DM2. Methods. Twenty-eight subjects were implanted with a VBLOC device (Maestro Rechargeable System) at 5 centers in an open-label study. Effects on weight loss, HbA1c, fasting blood glucose, and BP were evaluated at 1 week to 12 months. Results. 26 subjects (17 females/9 males, 51 ± 2 years, BMI 37 ± 1 kg/m2, mean ± SEM) completed 12 months followup. One serious adverse event (pain at implant site) was easily resolved. At 1 week and 12 months, mean excess weight loss percentages (% EWL) were 9 ± 1% and 25 ± 4% (P < 0.0001), and HbA1c declined by 0.3 ± 0.1% and 1.0 ± 0.2% (P = 0.02, baseline 7.8 ± 0.2%). In DM2 subjects with elevated BP (n = 15), mean arterial pressure reduced by 7 ± 3 mmHg and 8 ± 3 mmHg (P = 0.04, baseline 100 ± 2 mmHg) at 1 week and 12 months. All subjects MAP decreased by 3 ± 2 mmHg (baseline 95 ± 2 mmHg) at 12 months. Conclusions. VBLOC was safe in obese DM2 subjects and associated with meaningful weight loss, early and sustained improvements in HbA1c, and reductions in BP in hypertensive DM2 subjects. This trial is registered with ClinicalTrials.gov NCT00555958.

Improvements in obesity and glycemic control were largely sustained after 2 years of treatment with VBLOC therapy with a well-tolerated risk profile.

1. Because the inspiratory mechanical advantage of the canine parasternal intercostal muscles is greatest in the third interspace and decreases gradually in the caudal direction, the electromyograms of these muscles in interspaces 3, 5 and 7 have been recorded in anaesthetized, spontaneously breathing dogs. Each activity was expressed as a percentage of the activity measured during tetanic, supramaximal stimulation of the internal intercostal nerv,e (maximal activity). 2. Parasternal inspiratory activity during resting, room air breathing was invariably greater in the third than in the fifth interspace (62-0 + 6-0 vs. 41P3 + 4-6% of maximal activity; P < 0'001) and smallest in the seventh interspace (22-8 + 2-7% of maximal activity; P< 0-001). This distribution of activity persisted during hyperoxic hypercapnia and during breathing against increased inspiratory airflow resistance.3. This rostrocaudal distribution of activity also persisted after complete paralysis of the diaphragm as well as after deafferentation of the ribcage. 4. Studies of the distribution of the muscle fibre types indicated that the parasternal intercostals in all interspaces had a higher proportion of slow-twitch oxidative (SO; type I) fibres than fast-twitch oxidative-glycolytic (FOG; type II a) fibres. 5. Thus the topographic distribution of parasternal inspiratory activity along the rostrocaudal axis of the ribeage is precisely matched with the topographic distribution of mechanical advantage. This extraordinarily effective pattern of activation probably results from the unequal distribution of central inputs throughout the parasternal motoneurone pool.

No abstract

We investigated the regional distribution of blood flow (Q) within the costal and crural portions of the diaphragm in a total of eight anesthetized supine mongrel dogs. Q was measured with 15-microns microspheres, radiolabeled with three different isotopes, injected into the left ventricle during spontaneous breathing (SB), inspiratory resistive loading (IR), and mechanical ventilation after paralysis (P). At necropsy, the costal and crural portions of each hemidiaphragm were arbitrarily subdivided along a sagittal plane into five to seven and three sections, respectively. During P, there was a dorsoventral Q gradient within the costal part of the diaphragm. During SB there was a fourfold increase in the gradient of Q. Furthermore, during IR, in which mouth pressures of -16 +/- 4 cmH2O were generated, there was a further increase in the gradient of Q. During both SB and IR, Q to the most ventral portion of the costal diaphragm was 26 +/- 6% less than the peak value. In two dogs, studied prone and supine, there was no difference in the Q gradients between the two postures. Over the dorsal 80% of the costal diaphragm there was also a dorsoventral gradient of muscle thickness, such that the most dorsal part was 54 +/- 2% (n = 5) that of the ventral portion. In contrast, there was no consistent gradient of Q or muscle thickness within the crural diaphragm. Our results demonstrate a topographical gravity-independent distribution of Q in the costal, but not the crural, diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)

We studied respiratory-related activity of the soft palate muscles in 10 anesthetized tracheostomized supine dogs. Moving time average (MTA) electromyographic (EMG) activity was measured in the palatinus (PAL), levator veli palatini (LP), and tensor veli palatini (TP) with bipolar fine-wire electrodes and in the diaphragm with bipolar hook electrodes. Measurements were made during tracheostomy breathing and nasal breathing with the mouth sealed (NB). During tracheostomy breathing, all soft palate muscles displayed respiratory-related phasic inspiratory and expiratory as well as tonic EMG activity. During NB, peak inspiratory EMG activity increased in PAL, LP, and TP because of an increase in both phasic inspiratory and tonic MTA activity. In contrast, phasic expiratory activity did not change. A constant negative pressure equal to peak inspiratory tracheal pressure during NB was applied to the caudal end of the isolated upper airway with the nose occluded. This was associated with soft palate muscle responses qualitatively similar to the responses during NB but accounted for only 39, 25, and 32% of the magnitude of the peak inspiratory MTA EMG responses to NB in PAL, LP, and TP, respectively. Our results demonstrate that the soft palate muscles exhibit respiratory-related activity in common with other upper airway muscles. Furthermore, such activity is augmented in each soft palate muscle during NB, and negative upper airway pressure makes a substantial contribution to the recruitment of soft palate muscle activity.