PET for evaluation of differential myocardial perfusion dynamics after VEGF gene therapy and laser therapy in end-stage coronary artery disease.

The purpose of this study was to appraise the value of PET in the assessment of the effect of supposedly proangiogenic new therapies such as gene therapy with vascular endothelial growth factor (VEGF) gene and endomyocardial laser therapy. METHODS: Thirty-five patients with end-stage coronary artery disease and class III (Canadian Cardiovascular Society) angina were included. Myocardial ischemia was evaluated with dipyridamole PET scanning and exercise tolerance with bicycle ergometry. Ten patients were treated with naked plasmid DNA encoding for human VEGF165 (VEGF) and 12 patients were treated with laser therapy (direct myocardial revascularization [DMR]) using an electromechanical mapping system. Thirteen patients were treated with standard medical therapy (control). RESULTS: In both active treatment groups, angina was reduced in most subjects, except in 2 VEGF and 5 DMR patients. In the control group, no improvement in anginal classification was found, except in 3 subjects. On the PET scan, solely in the VEGF group, the stress perfusion was significantly improved (from 57 +/- 33 to 81 +/- 55 mL/min/100 g; P = 0.031). Furthermore, in the VEGF group, the number of ischemic segments was reduced from 274 +/- 41 to 234 +/- 48 segments (P = 0.004) but not in the DMR group (from 209 +/- 43 to 215 +/- 52 segments) or in the control group (from 218 +/- 18 to 213 +/- 28 segments). Bicycle exercise duration showed slight nonsignificant changes in the VEGF group (from 3.6 +/- 2.0 to 4.6 +/- 2.1 min), in the DMR group (from 5.1 +/- 1.5 to 4.7 +/- 1.3 min), and in the control group (from 3.3 +/- 1.8 to 3.5 +/- 2.3 min). CONCLUSION: PET showed that intramyocardial gene therapy with the human VEGF165 gene in contrast to laser DMR treatment effectively reduces myocardial ischemia.     

Optimum cycle frequencies in hand-rim wheelchair propulsion

Summary To study the effect of different cycle frequencies on cardio-respiratory responses and propulsion technique in hand-rim wheelchair propulsion, experienced wheelchair sportsmen (WS group; n=6) and non-wheel chair users (NW group; n=6) performed wheelchair exercise tests on a motor-driven treadmill. The WS group wheeled at velocities of 0.55, 0.83, 1.11 and 1.39 m · s^–1 and a slope of 2°. The NW group wheeled at 0.83, 1.11 and 1.39 m · s^–1 and a 1° slope. In each test, a 3-min period at a freely chosen cycle frequency (FCF: 100%) was followed by four 3-min blocks of paced cycle frequencies at 60%, 80%, 120% and 140% FCF. Effects of both cycle frequency and velocity on physiological and propulsion technique parameters were studied.Analysis of variance showed a significant effect (p<0.05) of cycle frequency on oxygen cost and gross mechanical efficiency in both the WS and NW group. This indicated the existence of an optimum cycle frequency which is close to the FCF at any given velocity. The optimum cycle frequency increased with velocity from 0.67 to 1.03 cps over the range studied (p< 0.05). Oxygen cost was 10% less at 100% FCF than at 60% or 140% FCF. Gross mechanical efficiency for the WS group at 100% FCF was 8.5%, 9.7%, 10.4% and 10.1%, respectively, at the four velocities. The similarity in the trend of oxygen cost and gross mechanical efficiency data in both the WS and NW groups suggests that an optimum cycle frequency is not merely a consequence of practice alone, but also reflects a physiologically determined optimum, dependent on muscle mechanics, e.g. velocity of contraction and power output of the muscles used.     

Peak oxygen uptake and maximal power output of Olympic wheelchair-dependent athletes.

To extend the existing data base on the cardiovascular capacity of wheelchair-dependent athletes, a maximum wheelchair exercise test was conducted by 48 athletes (8 females and 40 males) on a motor driven treadmill. Athletes were selected on availability from the representatives of eight different disciplines. For 36 subjects maximal external power was calculated on the basis of a separate drag test. Maximal oxygen uptake (VO2max) for the male population was 2.23 l.min-1 (32.9 ml.kg-1.min-1). Subjects were divided into functional categories according to the International Stoke Mandeville Classification, with one nonambulatory, nonparaplegic group classified as "LA." The LA group displayed the highest values while the class IC tetraplegic showed the lowest performance level. Classified over sports disciplines, male track and field representatives showed the highest VO2max (2.86 l.min-1, 44.9 ml.kg-1.min-1) and target shooting athletes the lowest (1.32 l.min-1, 16.3 ml.kg-2.min-1). Maximal power output was on average 81.1 W for the male population and varied from 65.8 W for class II athletes to 92.2 W for class LA. Between sports values ranged from 96.8 W for basketball players to 48.2 W for the archery representative. These data are useful for setting standards for maximally attainable performance levels in relation to sport, functional classification, or sex and underline the capability of the wheelchair-dependent to improve cardiovascular fitness.     

Photosensitized production of hydrogen by hydrogenase in reversed micelles

Hydrogenase (hydrogen:ferricytochrome c₃ oxidoreductase, EC 1.12.2.1) from Desulfovibrio vulgaris was encapsulated in reversed micelles with cetyltrimethylammonium bromide as surfactant and a chloroform/octane mixture as solvent. Reducing equivalents for hydrogenase-catalyzed hydrogen production were provided by vectorial photosensitized electron transfer from a donor (thiophenol) in the organic phase through a surfactant-Ru²⁺ sensitizer located in the interphase to methyl viologen concentrated in the aqueous core of the reversed micelle. The results show that reversed micelles provide a microenvironment that (i) stabilizes hydrogenase against inactivation and (ii) allows an efficient vectorial photosensitized electron and proton flow from the organic phase to hydrogenase in the aqueous phase.     

Non-invasive bladder volume measurement for the prevention of postoperative urinary retention: validation of two ultrasound devices in a clinical setting

Ultrasound scanning of bladder volume is used for prevention of postoperative urinary retention (POUR). Accurate assessment of bladder volume is needed to allow clinical decision-making regarding the need for postoperative catheterization. Two commonly used ultrasound devices, the BladderScan® BVI 9400 and the newly released Prime® (Verathon Medical®, Bothell, WA, USA), with or without the ‘pre-scan’ option, have not been validated in clinical practice. The aim of this study was to assess the performance of these devices in daily clinical practice. Between June and September 2016 a prospective observational study was conducted in 318 surgical patients (18 years or older) who needed a urinary catheter perioperatively for clinical reasons. For acceptable performance, we required that the volume as estimated by the BladderScan® differs by no more than 5% from the actual urine volume after catheterization. The Schuirmann’s two one-sided test was performed to assess equivalence between the BladderScan® estimate and catheterization. The BVI 9400® overestimated the actual bladder volume by +?17.5% (95% CI +?8.8 to +?26.3%). The Prime® without pre-scan underestimated by ? 4.1% (95% CI ? 8.8 to +?0.5%) and the Prime® with pre-scan underestimated by ? 6.3% (95% CI ? 11.6 to ? 1.1%). This study shows that while both ultrasound devices were able to approximate current bladder volume, both BVI 9400® and Prime®—with and without pre-scan—were not able to measure the actual bladder volume within our predefined limit of ±?5%. Using the pre-scan feature of the Prime® did not further improve accuracy.     

Shoulder biomechanics: today’s consensus and tomorrow’s perspectives

Shoulder biomechanics is a fast growing field, which is progressively expanding its focus to include more applied research. The papers included in this Special Issue confirm this trend. After a classification of the papers as dealing with fundamental or applied research through theoretical or experimental methods, in this Editorial we tried to summarize the elements of consensus and the open issues discussed during the last International Shoulder Group meeting, held in Bologna (Italy) in 2008.     

Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial

BACKGROUND: Folic acid is assumed to have favourable effects on vascular endothelium, directly as well as indirectly through its effect on homocysteine metabolism. However, the clinical value of folic acid in secondary prevention after acute myocardial infarction (MI) has never been tested. Thus, a randomised, open-label, multicentre trial was performed in order to study the effect of folic acid 5 mg o.d. when added to statin therapy on the incidence of recurrent major clinical events up to 1 year post-MI. METHODS: A total of 283 patients with a total cholesterol >6.5 mmol/l (251 mg/dl) (mean 7.3 mmol/l) were included. All patients received 40 fluvastatin. In 140 of the 283 patients, folic acid (5 mg o.d.) was instituted at discharge, and the remaining 143 patients served as controls. Other secondary prevention measures for both groups were advocated. The primary endpoint was a composite consisting of all vascular events, including death, recurrent MI, strokes, and unplanned invasive coronary interventions. RESULTS: At baseline, the two groups were well-matched for all clinical and demographic parameters. After 1 year of treatment, no difference was noticed in the primary endpoint between the two groups. These endpoints occurred in 43 patients (31%) in the folic acid group, as opposed to 45 patients (31%) in the control group. All separate cardiovascular events were also equally distributed between both groups. Total cholesterol levels decreased to a similar extent in the two groups (to 5.5 and 5.7 mmol/l, in folic acid and control groups, respectively). CONCLUSIONS: In this medium-size pilot study, folic acid did not demonstrate any beneficial additive effects on cardiovascular mortality or morbidity in post-MI patients with hypercholesterolemia who were treated with statin therapy. Larger trials, possibly targeting at selected populations, must be awaited before definitive conclusions regarding the potentially favourable effects of folic acid supplementation in secondary prevention can be drawn.     

Influence of hemodilution of plasma proteins on erythrocyte aggregability: an in vivo study in patients undergoing cardiopulmonary bypass

Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB) surgery. Blood samples were taken before, during, and after operation from 40 coronary artery bypass grafting patients who were operated with CPB and concomitant hemodilution (CPB, n=20) and who without (nonCPB, n=20). Erythrocyte aggregation was determined with a LORCA aggregometer, during which all samples were standardized to a hematocrit level of 40%. Results showed that in the CPB patients the aggregation index (AI) dropped to 44% of its preoperative baseline level 5 minutes after the start of hemodilution (from 47.7+/-10.1 to 26.6+/-11.4, p<0.01). Meanwhile, plasma concentration of fibrinogen (Fb) dropped to 55%, haptoglobin to 85%, ceruloplasmin to 55%, and albumin to 67%. In the nonCPB patients, however, there was only a slight drop in AI and the concentrations of plasma proteins during the similar period of time. On postoperative day 1, AI was rebounded to 37.1+/-12.4 in CPB patients compared with 44.3+/-11.7 in nonCPB patients. At baseline, AI was correlated only with Fb. During CPB and hemodilution, AI was correlated not only with Fb but also with haptoglobin and ceruloplasmin. Postoperatively, significant correlationship was found between AI and Fb, CRP, haptoglobin, ceruloplasmin, as well as albumin. These results indicate that hemodilution of plasma proteins significantly reduces the aggregability of erythrocytes in patients undergoing CPB. Besides Fb, other plasma proteins also contribute to AI during the early postoperative period when patients are recovering from CPB surgery.     

Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation?

OBJECTIVES: The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide. BACKGROUND: Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR). METHODS: One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible. RESULTS: AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P < .001). When flecainide was administered within 10 hours after AF onset and the duration of SR was greater than 4 days, the success rate was 58%. CONCLUSIONS: Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent AF.