SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: a randomised controlled trial.

BACKGROUND AND AIMS: Sodium tissue content by 23Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action. MATERIALS AND METHODS: In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7.6 years) with type 2 diabetes were randomized to either dapagliflozin 10 mg or placebo once daily for 6 weeks each. In addition to metabolic parameters and ambulatory blood pressure (BP) we analysed the sodium content in the skin and muscles of the lower leg by Na-MRI. RESULTS: Compared to baseline 6 weeks treatment with the SGLT-2 inhibitor dapagliflozin decreased fasting (132 ± 28 vs. 114 ± 19 mg/dl, p < 0.001), postprandial blood glucose (178 ± 66 mg/dl vs. 153 ± 46 mg/dl, p < 0.001), body weight (87.6 vs. 86.6 kg, p < 0.001) and systolic (129 ± 12 vs. 126 ± 11 mmHg, p = 0.010), and diastolic (77.4 ± 9 vs. 75.6 ± 8 mmHg, p = 0.024), 24-h ambulatory BP. Tissue sodium content in the skin was reduced after 6 weeks treatment with dapagliflozin compared to baseline [24.1 ± 6.6 vs. 22.7 ± 6.4 A.U.(arbitrary unit) p = 0.013]. No significant reduction of tissue sodium content was observed in the muscle (M. triceps surae: 20.5 ± 3.5 vs. 20.4 ± 3.7 A.U. p = 0.801). No clear significant difference in tissue water content of muscle and skin was observed after 6 weeks of treatment with dapagliflozin, compared to baseline. CONCLUSION: SGLT-2 inhibition with dapagliflozin resulted in a significant decrease in tissue sodium content of the skin after 6 weeks. This observation point to a decrease of total sodium content in patients with type 2 diabetes prone to cardiovascular complications, that might be mitigated by SGLT-2 inhibition. Trial registration The study was registered at http://www.clinicaltrials.gov (NCT02383238) retrospectively registered.

Atrophy of calf muscles by unloading results in an increase of tissue sodium concentration and fat fraction decrease: a 23Na MRI physiology study.

PURPOSE: 23Na MRI demonstrated increased tissue sodium concentrations in a number of pathologies. Acute atrophy results in muscle fibre volume shrinking that may result in a relative increase of extracellular volume and might affect sodium concentration. Thus, we hypothesized that local unloading of the calf muscles would lead to a decrease in muscle volume and an increase in muscle tissue sodium concentration. METHOD: One lower leg of 12 healthy male subjects was submitted to a 60 day long period of unloading using the Hephaistos orthosis, while the other leg served as control. 23Na MRI and 2D PD-weighted Dixon turbo spin echo were obtained from the control and orthosis leg using a 3T scanner. For quantification, a sodium reference phantom was used with 10, 20, 30, and 40 mmol/L NaCl solution. RESULT: Tissue sodium concentration (TSC) increased as an effect of unloading in the orthosis leg. Relative increases were 17.4 ± 16.8% (P = 0.005) in gastrocnemius medialis muscle, 11.1 ± 12.5 (P = 0.037) in gastrocnemius lateralis muscle, 16.2 ± 4.7% (P < 0.001) in soleus muscle, 10.0 ± 10.5% (P = 0.009) in the ventral muscle group, and 10.7 ± 10.0% (P = 0.003) in the central muscle group, respectively. TSC in the control leg did not significantly change. In the orthosis leg, muscle volume decreased as follows: medial gastrocnemius muscle: -5.4 ± 8.3% (P = 0.043) and soleus muscle: -7.8 ± 15.0% (P = 0.043). CONCLUSION: Unloading atrophy is associated with an increase in muscle sodium concentration. 23Na MRI is capable of detecting these rather small changes.

Long-term follow-up and resection of a postoperative false aortic aneurysm.

This report describes the course and operative findings in a 66-year-old man with a densely calcified false aneurysm of his ascending aorta 19 years after replacement of a severely stenosed bicuspid aortic valve with a McGovern-Chromie prosthesis. This report emphasizes the need to consider this possibility, even in patients with a very remote prior operation.

Compressive strength after blast of sandwich composite materials.

Composite sandwich materials have yet to be widely adopted in the construction of naval vessels despite their excellent strength-to-weight ratio and low radar return. One barrier to their wider use is our limited understanding of their performance when subjected to air blast. This paper focuses on this problem and specifically the strength remaining after damage caused during an explosion. Carbon-fibre-reinforced polymer (CFRP) composite skins on a styrene-acrylonitrile (SAN) polymer closed-cell foam core are the primary composite system evaluated. Glass-fibre-reinforced polymer (GFRP) composite skins were also included for comparison in a comparable sandwich configuration. Full-scale blast experiments were conducted, where 1.6×1.3 m sized panels were subjected to blast of a Hopkinson-Cranz scaled distance of 3.02 m kg(-1/3), 100 kg TNT equivalent at a stand-off distance of 14 m. This explosive blast represents a surface blast threat, where the shockwave propagates in air towards the naval vessel. Hopkinson was the first to investigate the characteristics of this explosive air-blast pulse (Hopkinson 1948 Proc. R. Soc. Lond. A 89, 411-413 (doi:10.1098/rspa.1914.0008)). Further analysis is provided on the performance of the CFRP sandwich panel relative to the GFRP sandwich panel when subjected to blast loading through use of high-speed speckle strain mapping. After the blast events, the residual compressive load-bearing capacity is investigated experimentally, using appropriate loading conditions that an in-service vessel may have to sustain. Residual strength testing is well established for post-impact ballistic assessment, but there has been less research performed on the residual strength of sandwich composites after blast.

Influence of short-term versus prolonged cardiopulmonary receptor stimulation on renal and preganglionic adrenal sympathetic nerve activity in rats.

Renal and preganglionic adrenal sympathetic nerve activities (RSNA, ASNA) are regulated differentially. Various cardiopulmonary receptor (CPR) stimulation procedures were performed to distinguish short-term and prolonged as well as mechanical and chemical stimulatory effects on RSNA and ASNA. In anesthetized male Sprague-Dawley rats blood pressure, heart rate, left ventricular end-diastolic pressure (LVEDP), RSNA and ASNA were recorded. CPRs were stimulated as follows: Short-term mechanical: LVEDP changes (+/-4, +/-6, +/-8 mmHg) via aortic and caval vein occlusion; Short-term chemical: phenylbiguanide (PBG-bolus, 0.1, 1, 10 microg IV); Prolonged mechanical (15 min): volume expansion (0.9% NaCl, 5% body weight) and hemorrhage, to modulate LVEDP; Prolonged chemical: PBG infusion (32 microg/min IV, for 15 min); Stimulations were done with 1) all afferents intact, 2) bilateral cervical vagotomy (VX), 3) VX + SAD (sino-aortic denervation; short-term protocols and hemorrhage).1) Short-term mechanical stimuli decreased RSNA (-52 +/- 12%) and ASNA (-37 +/- 13%). 2) PBG-bolus decreased RSNA (-54 +/- 12%) but increased ASNA (+40 +/- 13%). 3) Volume expansion decreased RSNA (-55 +/- 7%), ASNA was unaffected. 4) PBG infusion persistently decreased RSNA (-60 +/- 6%) but just shortly increased ASNA (+120 +/- 15%); VX abolished all responses. 5) Hypotensive hemorrhage decreased RSNA (-39 +/- 9%) but increased ASNA (+42 +/- 9%). VX abolished RSNA response; ASNA response only disappeared with VX + SAD.Short-term mechanical CPR stimulation uniformly decreased sympathetic activities, whereas chemical stimulation had opposing effects on renal and adrenal sympathetic responses. All prolonged stimuli decreased RSNA, whereas ASNA was virtually unaffected: Sympathetic out.ow is differentially controlled not only with regard to target organs or afferent receptors but also stimulus time pattern.

Prevalence and characteristics of pharyngeal group A beta-hemolytic streptococci in US Navy recruits receiving benzathine penicillin prophylaxis.

US military recruits receive benzathine penicillin prophylaxis because of endemicity of group A beta-hemolytic streptococcal (GABHS) infections. GABHS prevalence in Navy recruits receiving single-dose benzathine penicillin prophylaxis was assessed during spring and fall 1989 by culturing throat specimens from randomly selected groups of approximately 230 men before and 2, 4, and 7 weeks after prophylaxis and from men with pharyngitis diagnosed at sick call. Of 60 GABHS isolates, 75% were serotype M-3. The pharyngitis rate increased from 0.18% in the spring to 1.55% in the fall with a concurrent increase in serotype M-3 prevalence from 35% to 91%. The GABHS prevalence rate was three- to fourfold lower after prophylaxis. There were no cases of acute rheumatic fever (ARF) despite predominance of M-3, a rheumatogenic serotype. It was concluded that penicillin prophylaxis continues to be effective for control of GABHS infections and prevention of ARF in Navy recruits.