Asymmetric and Symmetric Dimethylarginine and Sympathetic Nerve Traffic after Renal Denervation in Patients with Resistant Hypertension

Background and objectives

The plasma concentration of the endogenous inhibitor of nitric oxide synthase asymmetric dimethylarginine (ADMA) associates with sympathetic activity in patients with CKD, but the driver of this association is unknown.

Design, setting, participants, & measurements

In this longitudinal study (follow-up: 2 weeks–6 months), repeated measurements over time of muscle sympathetic nerve activity corrected (MSNAC), plasma levels of ADMA and symmetric dimethylarginine (SDMA), and BP and heart rate were performed in 14 patients with drug-resistant hypertension who underwent bilateral renal denervation (enrolled in 2013 and followed-up until February 2014). Stability of ADMA, SDMA, BP, and MSNAC over time (6 months) was assessed in two historical control groups of patients maintained on stable antihypertensive treatment.

Results

Time-integrated changes in MSNAC after renal denervation ranged from –40.6% to 10% (average, –15.1%), and these changes were strongly associated with the corresponding changes in plasma ADMA (r= 0.62, P=0.02) and SDMA (r=0.72, P=0.004). Changes in MSNAC went along with simultaneous changes in standardized systolic (r=0.65, P=0.01) and diastolic BP (r=0.61, P=0.02). In the historical control groups, no change in ADMA, SDMA, BP, and MSNAC levels was recorded during a 6-month follow-up.

Conclusions

In patients with resistant hypertension, changes in sympathetic activity after renal denervation associate with simultaneous changes in plasma levels of the two major endogenous methylarginines, ADMA and SDMA. These observations are compatible with the hypothesis that the sympathetic nervous system exerts an important role in modulating circulating levels of ADMA and SDMA in this condition.     

Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives

BACKGROUND: Previous studies have shown that obesity is characterized by a sympathetic overactivity coupled with an insulin resistance state and a baroreflex impairment. The present study was set out to compare the effects of peripheral versus central obesity on sympathetic, metabolic and reflex function. METHODS: In 36 lean subjects (age 35.8 +/- 1.4 years, mean +/- SEM), 20 subjects with peripheral obesity (PO) and 26 subjects with central obesity (CO), all age-matched and with normal blood pressure values, we measured beat-to-beat arterial blood pressure (Finapres), heart rate (HR, ECG), homeostasis model assessment (HOMA) index, plasma norepinephrine (NE, high-performance liquid chromatography) and postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Both HOMA index, NE and MSNA values were significantly increased (P < 0.01) in obese as compared with lean individuals. Subjects with CO displayed MSNA and HOMA values significantly greater than those found in individuals with PO (65.4 +/- 2.0 versus 47.9 +/- 1.9 bs/100hb and 2.85 +/- 0.10 versus 2.43 +/- 0.11 a.u., respectively, P < 0.05 for both). Both in male and female subjects with CO or PO, MSNA, HOMA index and waist-to-hip ratio were significantly related to each other. Baroreceptor-HR and -MSNA control was significantly (P < 0.01) impaired in obese as compared with lean subjects, the degree of impairment being similar in CO and PO. CONCLUSIONS: These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.     

Barium peritonitis: experimental study using barium sulfate and radioactive barium

Barium peritonites are known to be a serious complication of barium enema examinations, being accompanied by a high mortality rate. The authors made their study injecting barium and radioactive 133Ba in the peritoneum of 68 rats without causing damages to the colon, in order to verify the toxicity of barium if injected in the peritoneum, and to evaluate the various extraperitoneal locations. Moreover, they compared the alterations caused by this agent with those consequent to a similar agent, such as talcum. The results show that barium is not toxic on its own: it gives in fact origin to granulomas similar to those caused by talcum; a particular tropism for the lymphatic tissues is present as well.     

Late cardiac perforation after transcatheter closure of patent foramen ovale

Cardiac perforation after transcatheter closure of a patent foramen ovale is a very rare complication. We report a case of left atrial wall perforation and aortic root erosion occurring 16 months after implantation of an Amplatzer patent foramen ovale occluder that required emergent surgery.     

Resolution of a Pseudomonas aeruginosa outbreak in a hematology unit with the use of disposable sterile water filters

We observed a significant increase of Pseudomonas aeruginosa bacteremias during 2002. Eighty-five microbiological samples were taken from different potential sources of infection. Twenty-nine out of 46 specimens obtained from water taps, shower heads and siphons tested positive for Pseudomonas aeruginosa. Weekly pharyngeal and rectal swabs in high risk patients, use of tap water after running the tap for at least 5 minutes and use of weekly disposable sterile filters in all taps and showers resulted in a significant decrease in Pseudomonas aeruginosa bacteremias. Moreover, we observed a significant reduction in Pseudomonas aeruginosa-positive surveillance cultures after implementation of these measures.     

Lymphocyte subsets in inline filtered packed red blood cell units: comparison between low and high spin procedures.

Lymphocyte subsets were determined in 20 packed red blood cell units (PRC) before and after filtration (FPRC) with the Pall Leukotrap RC inline filter system; 10 units were prepared by low spin and platelet rich plasma (PRP) removal (Group A) and 10 with high spin, plasma and buffy-coat (BC) removal (Group B). Flow cytometry was employed for white blood cell (WBC) enumeration and phenotype analysis. Median WBCs in prefiltered units was 2.08 x 10(9) (Group A) vs. 0.8 x 10(9) (Group B) (p < 0.0001). Five Group A and three Group B filtered units had WBC counts above the limit of detection (LD), median values being 25.59 and 3.08 x 10(3), respectively. Whereas CD3+, CD3+CD4+ and CD3+CD8+ lymphocyte subsets were assessable in 20-40% of Group A units, inline filtration of Group B units lowered lymphocytes below the LD of the present study. Post-filtration CD19+ lymphocytes were below the LD in all the 20 units.     

Phase development during setting and hardening of a bone cement based on α-tricalcium and octacalcium phosphates

In this study, the phase development in the cement system α-TCP-OCP with phosphoric acid as a setting liquid was studied. The most promising formulation of α-TCP (60?wt%) and OCP (40?wt%) is proposed. This cement has the following characteristics: setting time 10?min, pH?=?6.7, the compressive strength about 30?MPa, and high dissolution rate in an isotonic solution; the final wt% composition of α-TCP/DCPD/HA/OCP equals 27/38/20/15. Energy dispersive X-ray diffraction techniques were used for in situ monitoring of the processes taking place in the cement in real time.     

Early sympathetic activation in the initial clinical stages of chronic renal failure

Direct and indirect indices of neuroadrenergic function have shown that end-stage renal disease is characterized by a marked sympathetic overdrive. It is unknown, however, whether this phenomenon represents a peculiar feature of end-stage renal disease or whether it is also detectable in the early clinical phases of the disease. The study has been performed in 73 hypertensive patients, of which there were 42 (age: 60.7±1.8 years, mean±SEM) with a stable moderate chronic renal failure (mean estimated glomerular filtration rate: 40.7 mL/min per 1.73 m2, MDRD formula) and 31 age-matched controls with a preserved renal function. Measurements included anthropometric variables, sphygmomanometric and beat-to-beat blood pressure, heart rate (ECG), venous plasma norepinephrine (high-performance liquid chromatography), and efferent postganglionic muscle sympathetic nerve activity (microneurography, peroneal nerve). For similar anthropometric and hemodynamic values, renal failure patients displayed muscle sympathetic nerve activity values significantly and markedly greater than controls (60.0±2.1 versus 45.7±2.0 bursts per 100 heartbeats; P<0.001). Muscle sympathetic nerve activity showed a progressive and significant increase from the first to the fourth quartile of the estimated glomerular filtration rate values (first: 41.0±2.7; second: 51.9±1.7; third: 59.8±3.0; fourth: 61.9±3.3 bursts per 100 heartbeats), the statistical significance (P<0.05) between groups being maintained after adjustment for confounders. In the population as a whole, muscle sympathetic nerve activity was significantly and inversely correlated with the estimated glomerular filtration rate (r=-0.59; P<0.0001). Thus, adrenergic activation is a phenomenon not confined to advanced renal failure but already detectable in the initial phases of the disease. The sympathetic overdrive parallels the severity of the renal failure, state and, thus, it might participate, in conjunction with other factors, at the disease progression.