Collateral augmentation treatment with a combination of acetazolamide and head-down tilt in a rat ischemic stroke model

Cerebral collaterals is crucially important in the pathophysiology of acute ischemic stroke and associated with outcome after reperfusion therapy. We explored the effectiveness of collateral augmentation treatment with a combination of acetazolamide (ACZ) and head-down tilt (HDT) in the transient middle cerebral artery occlusion (MCAO) rat model. Transient MCAO was induced in all animals for 1.5 h, followed by reperfusion for 22.5 h. Seventy-two male Wistar rats were divided into four treatment groups: control, ACZ, HDT, and combination. Twenty sham rats, which underwent surgery, were randomly allocated to these groups. Twenty-four hours after MCAO or sham surgery, we measured the infarction volume, brain edema (aquaporin-4 [AQP4], and brain water content), and neurological deficits (Garcia and Longa tests). Collateral augmentation treatments were associated with reduced infarction volume, less brain edema, and better neurological outcomes compared with untreated animals. More specifically, ACZ and HDT treatments resulted in small infarction volumes, and HDT was associated with a low AQP4 expression and improved neurological score, while the combination of ACZ and HDT improved neurological scores and reduced brain water content. This study shows that collateral augmentation treatments are associated with a better stroke prognosis compared with untreated animals after transient MCAO. The combination of ACZ and HDT seems to have some synergistic effect, but was not proven to be superior to HDT treatment alone.     

A pilot study of complete edentulous rehabilitation with immediate function using a new implant design: case series

Background: The current investigation focuses on new implant designs for increased predictability in clinically demanding situations. Microtextured implant surfaces create favorable conditions for enhanced osseointegration of dental implants compared to implants with a smooth surface, and the macroscopic implant design may influence implant stability. Purpose: The aim of the present study was to retrospectively evaluate the clinical performance of a novel implant design in the rehabilitation of completely edentulous jaws and in combination with an immediate function protocol. Materials and Methods: Forty‐six consecutive patients received 189 study implants (NobelSpeedy^TM concept implant, Nobel Biocare AB, Göteborg, Sweden) supporting 53 full‐arch all‐acrylic prostheses (44 maxilla, 9 mandible). The majority (66%) of the reconstructions were supported by four implants, of which the two posterior implants were tilted. All patients were followed for a minimum of 1 year. Radiographic assessment of the marginal bone level was performed. Results: Two implants were lost in two patients, rendering a 1‐year cumulative clinical survival rate of 98.9%. The marginal bone level was, on average, situated 1.2 ± 0.7 mm below the implant‐abutment interface after 1 year of loading. Good soft tissue health and overall esthetic outcome was reported. Conclusions: The results of the present pilot study indicate that fully edentulous jaws with various types of bone can be treated with high success and good esthetics using immediately loaded implants with the presented design, and that favorable marginal bone levels can be maintained.     

Physical Training as Non-Pharmacological Treatment of Neurocardiogenic Syncope

Background

Characterized as a sudden and temporary loss of consciousness and postural tone, with quick and spontaneous recovery, syncope is caused by an acute reduction of systemic arterial pressure and, therefore, of cerebral blood flow. Unsatisfactory results with the use of drugs allowed the nonpharmacological treatment of neurocardiogenic syncope was contemplated as the first therapeutic option.

Objectives

To compare, in patients with neurocardiogenic syncope, the impact of a moderate intensity aerobic physical training (AFT) and a control intervention on the positivity of head-up tilting test (HUT) and orthostatic tolerance time.

Methods

Were studied 21 patients with a history of recurrent neurocardiogenic syncope and HUT. The patients were randomized into: trained group (TG), n = 11, and control group (CG), n = 10. The TG was submitted to 12 weeks of AFT supervised, in cycle ergometer, and the CG to a control procedure that consisted in 15 minutes of stretching and 15 minutes of light walk.

Results

The TG had a positive effect to physical training, with a significant increase in peak oxygen consumption. The CG did not show any statistically significant change before and after the intervention. After the intervention period, 72.7% of the TG sample had negative results to the HUT, not having syncope in the revaluation.

Conclusion

The program of supervised aerobic physical training for 12 weeks was able to reduce the number of positive HUT, as it was able to increase tolerance time in orthostatic position during the HUT after the intervention period.     

Cutaneous and subcutaneous blood flow rates in paraplegic humans investigated by 133Xenon wash-out. Methodological considerations

Summary. In a methodological study including 14 paraplegics and seven normal controls cutaneous and subcutaneous blood flow rates were investigated by ¹³³Xenon wash-out after atraumatic labelling. In paraplegics, areas suffering pressure sores were included. The method was found applicable for the authors' purposes. In seven paraplegics median (95% confidence limits) cutaneous blood flow was 5–2 (2–4–8–5) ml (100 g min)“¹ and subcutaneous 4–3 (2–0–13–2) ml (100 g min)^-1. This did not differ from normal controls. In seven paraplegics with ischial pressure sores a trend for increased cutaneous blood-flow rates from areas adjacent to sores was obvious (P= 0–06). During 704 head-up tilt, elimination-rate constants were reduced by a factor of 0–54 (0–50–0–70). A proximal blockade or infiltration of the ¹³³Xenon depots with lidocaine did not inhibit employment of the method. The proximal block did not alter the local blood flow rate, but infiltration increased it in both paraplegics and normal individuals. Intra- and interdepot coefficients of variation were about 11% and 40% respectively. Interindividual coefficients of variation varied between 25% and 46%.     

Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation

We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na⁺ and K⁺) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P<0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal·24 h^–1 to 2,450 (36) kcal·24 h^–1, where 1 kcal·h^–1=1.163 J·s^–1; P<0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K⁺ excretion was unchanged during HDBR, whereas for Na⁺ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na⁺ rhythm and abolition of the aldosterone rhythm. Electronic Publication     

Skinfold thickness versus isotope dilution for body fat assessment during simulated microgravity: results from three bed-rest campaigns in men and women with and without countermeasures

Because body composition is altered during head-down bed rest (HDBR), body mass can not be used as an index of energy balance. Consequently diet allowances should not be based on body mass evolution but on fat mass changes. Though criticized, skinfold thickness (ST) is the costless, easiest and fastest method to use for such an objective. The aim of this study was to compare the percentage of body fat (%BF) estimated by ST with the isotope dilution of H₂¹⁸O. We compiled data from three HDBR campaigns, one on women (n=8) in November 1998 and two on the same men (n=8) in December 1997 (without countermeasure) and January 1998 (with thigh-cuffs countermeasure), according to a crossover design. Body composition was assessed before and after 6 days of HDBR. %BF was derived from the biceps, triceps, sub-scapular and sup-iliac ST according to Durnin and Wormersly (1974). Fat-free mass was measured on the same day by H₂¹⁸O dilution and fat mass was calculated by the difference with body mass and expressed as a percentage. Based on precision tests, the minimum measurable change by ST was 1.1%BF for single measurement point. Both intercepts (F _4,30=0.89, P=0.45) and slopes (F _4,30=0.74; P=0.57) of the ST versus dilution relationships were not affected by the periods (December vs January), experimental conditions (control vs HDBR vs HDBR + thigh cuffs) or sex allowing the derivation of a common relationship %BF_st=0.94 × %BF_dil (F _1,47=97.9, P<0.0001; non-significant intercept excluded) with a bias between methods of −1.7±2.0 %BF (95% CI: −5.8, 2.4 %BF). ST can be used to measure %BF during HDBR provided great care is placed on training and changes are higher than 1.1 %BF. If the method can be applied for in-flight energy balance monitoring given the high observed energy deficit, a tight monitoring of the individual nutritional status as needed during simulation appears, however, dubious based on this solely method.     

Hormone changes induced by 37.5-h head-down tilt (−6°) in humans

Endocrine regulation of hormones and electrolytes during 37.5 h of –6° head down tilt (HDT) was studied in 13 men. The acute effects of simulated weightlessness are today well documented, but no study has been made concerning the hormone changes between 12 h and 2 days of HDT. Plasma volume showed a maximal increase of 9.23 (SEM 1.97) % after 6.5 h (P<0.01) and had returned to prestudy levels after 13.5 h of HDT. From 1.5 h to 4 h of HDT, C-terminus and N-terminus atrial natriuretic peptide (ANP) concentrations in plasma were increased by about 50% (P<0.01) and thereafter declined to pre-HDT levels. Plasma renin activity (PRA) was decreased by 47% (P<0.05) after 4 h of HDT; PRA increased after 23.5 h to 60%; noradrenaline concentration decreased immediately and remained low up to 37.5 h. Diuresis and natriuresis were evident during the 1st day of HDT, resulting in a marked increase in the urinary Na⁺. These results showed that the initial hormone (ANP, PRA) changes during HDT did not last more than 13.5 h and that after 24 h a new state would seem to have been established to adapt the body to hypovolaemia.     

Hemodynamic and hormonal responses to lower body negative pressure in men with varying profiles of strength and aerobic power

Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake ( O_2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither O_2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge.     

Metabolic and cardiovascular responses during sub-maximal exercise in humans after 14 days of head-down tilt bed rest and inactivity

f _H, SV, [Hb], C_aO₂, O₂, MAP and R _P were measured in 10 young subjects at rest and during exercise at 50, 100 and 150 W before and after 14 days of head-down tilt bed rest (HDTBR) and of ambulatory (AMB) control period. f _H was 18 and 8% higher after HDTBR and AMB, respectively. SV dropped by 15% both after HDTBR and AMB, whereas did not change. After HDTBR, C_aO₂ decreased at rest (−8%) and at 50 W (−5%), whereas O₂ did not change; MAP was 14 and 6% lower at rest and at 100 W and R _P decreased by 23% only at rest. Changes in f _H and SV were larger after HDTBR than after AMB. These results show that, notwhistanding the drop of SV, moderate-intensity dynamic exercise elicited a normal pressure response after 14 days of HDTBR.     

Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects

Objective: Pharmacokinetics, pharmacodynamic effects and tolerability of 200?mg valsartan, once-daily for 8 days, were investigated in 16 healthy, normotensive volunteers on a normal sodium diet. Methods: This was a double-blind, placebo-controlled, randomized crossover study. Drug concentrations in plasma and urine, angiotensin II (Ang II) concentrations in plasma, systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) in the supine position and 3?min after passive head-up tilting, as well as safety parameters (ECG, clinical chemistry and hematology, renal water and electrolyte excretion) were measured over 24?h after the first dose (day 1) and at steady state on day 8. Results: Absorption and distribution of valsartan were rapid (C_max, 2?h; t_½λ1?½λ2, 6?h) on days 1 and 8, with little accumulation in plasma (increase of 20% on day 8). Less than 10% of the dose was excreted unchanged in urine. The increase in plasma Ang II (C_max, 6?h) was significantly enhanced at steady state. Supine SBP and DBP significantly decreased on day 8 only, by an average of ?3.6 and ?2.4?mmHg, respectively, versus placebo, without a concomitant increase in HR. Upon passive tilting, the increase in DBP, normally reinforced by sympathetic renin release, was slightly but significantly blunted on day 1 (?2.0?mmHg) and day 8 (?4.0?mmHg) of treatment with valsartan versus placebo. The orthostatic reflex increase in HR was slightly enhanced compared with placebo by an average of 2.8 beats?·?min^?1 on day 1 and by 2.9 beats?·?min^?1 on day 8. Valsartan was well tolerated and had no influence on ECG, clinical laboratory parameters, and water, electrolyte and uric acid excretion. Conclusions: Pharmacokinetics of valsartan are unchanged after multiple once-daily dosing, with little (expected) accumulation in plasma. Effects of 200?mg valsartan on blood pressure in healthy subjects on a normal sodium intake are small and become more prominent after repeated dosing. Indirect evidence of AT₁ blockade by valsartan is demonstrated by an increase of plasma Ang II and by a blunted DBP response to passive tilting. The decrease in blood pressure at steady state enhances the increase in plasma Ang II. Valsartan is well tolerated and is devoid of effects on water, electrolyte and uric acid excretion at 200?mg per day in healthy normotensive volunteers.