Clinical Characteristics of Patients Undergoing Right Heart Catheterizations in Community Hospitals.

Background Recognition of precapillary pulmonary hypertension (PH) has significant implications for patient management. However, the low a priori chance to find this rare condition in community hospitals may create a barrier against performing a right heart catheterization (RHC). This could result in misclassification of PH and delayed diagnosis/treatment of precapillary PH. Therefore, we investigated patient characteristics and echocardiographic parameters associated with the decision whether to perform an RHC in patients with incident PH in 12 Dutch community hospitals. Methods and Results In total, 275 patients were included from the OPTICS (Optimizing PH Diagnostic Network in Community Hospitals) registry, a prospective cohort study with patients with incident PH; 157 patients were diagnosed with RHC (34 chronic thromboembolic PH, 38 pulmonary arterial hypertension, 81 postcapillary PH, 4 miscellaneous PH), while 118 patients were labeled as probable postcapillary PH without hemodynamic confirmation. Multivariable analysis showed that older age (>60 years), left ventricular diastolic dysfunction grade 2-3, left atrial dilatation were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilatation, and tricuspid regurgitation velocity ≥3.7 m/s favor an RHC performance. Conclusions Older age and echocardiographic parameters of left heart disease were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilation, and severe PH on echocardiography favored an RHC performance. As such, especially elderly patients may be at an increased risk of diagnostic delays and missed diagnoses of treatable precapillary PH, which could lead to a worse prognosis.

Transcatheter edge-to-edge repair of tricuspid regurgitation in the Netherlands: state of the art and future perspectives.

Despite the high prevalence and adverse clinical outcomes of severe tricuspid regurgitation (TR), conventional treatment options, surgical or pharmacological, are limited. Surgery is associated with a high peri-operative risk and medical treatment has not clearly resulted in clinical improvements. Therefore, there is a high unmet need to reduce morbidity and mortality in patients with severe TR. During recent years, several transcatheter solutions have been studied. This review focuses on the transcatheter edge-to-edge repair of TR (TTVR) with respect to patient selection, the procedure, pre- and peri-procedural echocardiographic assessments and clinical outcomes. Furthermore, we highlight the current status of TTVR in the Netherlands and provide data from our initial experience at the University Medical Centre Groningen.

In ovo L-arginine supplementation stimulates myoblast differentiation but negatively affects muscle development of broiler chicken after hatching.

In this study, we tested the hypothesis that in ovo feeding (IOF) of L-arginine (L-Arg) enhances nitric oxide (NO) production, stimulates the process of myogenesis, and regulates post-hatching muscle growth. Different doses of L-Arg were injected into the amnion of chicken embryos at embryonic day (ED) 16. After hatching, the body weight of individual male chickens was recorded weekly for 3 weeks. During in vitro experiments, myoblasts of the pectoralis major (PM) were extracted at ED16 and were incubated in medium containing 0.01 mm L-Arg, 0.05 mm L-Arg, and (or) 0.05 mm L-nitro-arginine-methyl-ester (L-NAME), an inhibitor of nitric oxide synthase (NOS). When 25 mg/kg L-Arg/initial egg weight was injected, no difference was observed in body weight at hatch, but a significant decrease was found during the following 3 weeks compared to that of the non-injected and saline-injected control, and this also affected the growth of muscle mass. L-NAME inhibited gene expression of myogenic differentiation antigen (MyoD), myogenin, NOS, and follistatin, decreased the cell viability, and increased myostatin (MSTN) gene expression. 0.05 mm L-Arg stimulated myogenin gene expression but also depressed muscle cell viability. L-NAME blocked the effect of 0.05 mm L-Arg on myogenin mRNA levels when co-incubated with 0.05 mm L-Arg. L-Arg treatments had no significant influence on NOS mRNA gene expression, but had inhibiting effect on follistatin gene expression, while L-NAME treatments had effects on both. These results suggested that L-Arg stimulated myoblast differentiation, but the limited number of myoblasts would form less myotubes and then less myofibers, while the latter limited the growth of muscle mass.

Spread of hatch and delayed feed access affect post hatch performance of female broiler chicks up to day 5.

It is not rare that newly hatched chicks remain without feed for about 24 to 48 h before they are placed on farms due to a series of logistic operations. Furthermore, the spread in hatching time can also mount up to 30 to 48 h for late v. early hatchers. In other words, the practice is a complex combination of spread of hatch and delayed feed access. The present study was aimed to investigate the combined effects of hatching time with a delay in feed access of 48 h, starting from their hatch-time (biological age). When chicks had access to feed immediately after hatch, late hatchers had a higher feed intake and relative growth rate up to day 5 compared with their early hatched counterparts. Feed deprivation during the first 48 h resulted in retarded early growth rate, which was further aggravated by an impaired feed intake after refeeding. In addition, the differential effects of hatching time on relative growth rate and feed intake observed in immediately fed chicks were eliminated by the 48 h feed delay. The yolk utilization after hatch was faster for the late hatchers up to biological day 2 regardless of the feeding treatments. Hatching muscle glycogen content was higher in the late hatchers compared with that of their early counterparts at hatch and at biological day 2 independent of feeding treatment. Moreover, the liver glycogen content of the late hatchers was also higher at hatch. For the immediately fed chicks, the proportional breast muscle weight of the late hatchers was higher at biological day 2 and 5. For the starved chicks, on the other hand, this effect was only observed after they had access to feed (biological day 5). The different plasma T3 levels at hatch may have contributed to the different post hatch performance. It is concluded that the spread of hatch influenced post hatch performance, especially appetite and growth at least until day 5. Moreover, the delay in feed access interacted with the hatching time and caused adverse effects on the post hatch performance.

Effects of interaction of incubator CO2 levels and mixing hatching eggs of different embryo growth trajectory on embryo physiological and hatching parameters.

1. Two experiments were designed to investigate the effects of mixing eggs of different genotype and incubating with different CO2 concentrations on embryonic parameters. Half of the eggs were incubated in a CO2 controlled incubator (VCO2) during the first 10 d of incubation and the other half was incubated at standard incubation ventilation rate (SV). 2. From 10 to 18 d of incubation, thick albumen and embryos were weighed. Blood samples were collected at d 18 of incubation, at internal pipping and at hatch for determination of triiodothyronine (T3), thyroxine (T4) and corticosterone concentration. During the last 2 d of incubation, hatching events of individual eggs were monitored every 2 h. 3. From 4 to 5 d of incubation in the SV group of Experiment 1, pH values of Ross strain chickens were lower than those of Isa Brown. From d 12 of incubation onwards, Ross embryos grew faster than those of Isa Brown. At 14 and 16 d of incubation, Ross eggs in the CO2 controlled incubator had lower albumen weights compared to all other treatments. 4. T3 concentrations in Ross embryos were higher than those of Isa Brown embryos. Chicken weight at hatch was in the following order: Isa Brown SV < Isa Brown VCO2 = Ross SV < Ross VCO2. 5. In Experiment 2, incubation time of VCO2 eggs until internal pipping, external pipping and hatch was significantly shorter than that of SV eggs. 6. It was concluded that mixing of hatching eggs of differential embryo developmental trajectory affects their hatching process.

Partial albumen removal early during embryonic development of layer-type chickens has negative consequences on laying performance in adult life.

To examine the importance of albumen as a protein source during embryonic development on the posthatch performance of laying hens, 3 mL of the albumen was removed. At hatch, no difference in BW could be observed. Chicks from the albumen-deprived group had a lower residual yolk weight due to higher yolk utilization. During the rearing phase (hatch to 17 wk of age), the BW of the albumen-deprived pullets was lower compared with the control and sham pullets. The feed intake of the albumen-deprived pullets was also lower than the control pullets. However, during the laying phase (18 to 55 wk of age) these hens exceeded the control and sham hens in BW, although this was not accompanied by a higher feed intake. The albumen-deprived hens exhibited a lower egg production capacity as demonstrated by the reduced egg weight, laying rate, and egg mass and increased number of second grade eggs. In addition, the eggs laid by the albumen-deprived hens had a higher proportional yolk and lower proportional albumen weight. In conclusion, prenatal protein deprivation by albumen removal caused a long-lasting programming effect, possibly by differences in energy allocation, in favor of growth and maintenance and impairing reproductive performance.

Dehydration indicators for broiler chickens at slaughter.

Freedom of (prolonged) thirst is considered to be of paramount importance for animal welfare. This emotion normally results from dehydration, which can be measured using physiological indicators. Because no reliable physiological indicator for thirst was available for broilers, we aimed to identify such a measure in this study. This indicator would ideally be integrated into quality control systems in commercial slaughter plants. In the first experiment, water deprivation was manipulated systematically by withdrawing water for different durations (total water withdrawal for 0 (control), 24, 36, or 48 h, or a 10-d period with restricted access to water for 2 times 10 min per day). A significant decrease in drained blood content and BW occurred from 36 h of total water deprivation onward (both P = 0.03), whereas long-term restricted access tended to decrease drained blood content (P = 0.05). No effect of water deprivation or restriction on skin turgor was found. In the second experiment, water was withdrawn for 0 (control), 6, 12, 24, or 48 h. Plasma chloride concentration was increased after 6 h of water withdrawal, but did not rise further with longer withdrawal. If assessed at slaughter, chloride will thus mainly reflect the catching-to-slaughter interval. In contrast, plasma creatinine and hematocrit levels showed a numerical decrease after 6 h of water withdrawal, but rose again after prolonged withdrawal. Plasma creatinine values were significantly higher in 24-h-deprived birds than in 6-h-deprived birds (P < 0.01), allowing for discernment between water withdrawal during catching and transport from dehydration that had occurred on the farm. Blood sodium concentrations and plasma osmolality showed a steady increment between 0 and 24 h of water deprivation (P < 0.001 and P < 0.001 for both), and may thus be used to assess the combined effects of water deprivation on farm and during the catching-to-slaughter interval. These findings may form the basis of an on-farm or at-slaughter test that could be included in integrated animal welfare assessment schemes.

Interaction between ascites susceptibility and CO(2) during the second half of incubation of two broiler lines: the effect on post-hatch development and ascites mortality.

1. The aim of this study was to investigate if genetic predisposition to ascites interacts with changed incubation conditions, and how this might affect the post-hatch performance and ascites susceptibility. 2. An ascites sensitive (A) and resistant (E) broiler line were incubated under standard or high CO(2) conditions (up to 4%) from embryonic d 10 onwards. After hatch, chicks were exposed to cold from the 15th day of the rearing period to increase the incidence of ascites. 3. The A line had a higher post-hatch body weight from week three, higher blood pCO(2) from d 21, higher haematocrit at d 35 and d 42, and higher plasma corticosterone concentration from d 21 onwards, compared with the E line, regardless of incubation conditions, supporting the given selection criteria. Ascites mortality did not, however, differ between lines. 4. Incubation under high CO(2) conditions during the second half of incubation increased the ascites mortality, decreased body weight from week 4 onwards, affected venous blood pCO(2), decreased blood pO(2) from d 31, increased haematocrit at d 35 and d 42, and lowered the thyroxine and triiodothyronine concentrations at most sampling days. These effects were observed in both lines. The results suggested a metabolic programming of CO(2) incubated chickens which affected ascites susceptibility.

Evaluation of dietary stevioside supplementation on anti-human serum albumin immunoglobulin G, Alpha-1-glycoprotein, body weight and thyroid hormones in broiler chickens.

Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21 of age, ten birds from either the S (SH) or C (CH) group were injected subcutaneously with 100 µg human serum albumin (HSA) and ten others from either S (SP) or C (CP) group injected with 100 µl phosphate-buffered saline (PBS) in the same way. There were no significant effect of supplementation nor interaction with age on average body weights, T(3) and T(4) concentrations of non-injected chickens. After the primary immunization, α(1) -glycoprotein concentrations increased in all treatment groups except the CP group, and were significantly higher in the CH group in relation to the other groups. Fourteen and 18 days after the primary immunization, HSA injected chickens of both dietary treatments had significantly higher anti-HSA immunoglobulin G (IgG) levels than their PBS injected controls. No effect of stevioside supplementation was observed for IgG level. In conclusion, dietary stevioside inclusion can attenuate the pro-inflammatory response after stimulation of the innate immune response in broiler chickens.

Effects of dietary supplementation of methionine and its hydroxy analog DL-2-hydroxy-4-methylthiobutanoic acid on growth performance, plasma hormone levels, and the redox status of broiler chickens exposed to high temperatures.

Heat stress is known to impair performance and to induce oxidative stress in poultry. The aim of the present study was to compare the effects of dietary supplementation of dl-methionine (dl-M) or the synthetic analog 2-hydroxy-4-methylthiobutanoic acid (dl-HMTBA) on broiler growth performance, plasma hormone levels, and some oxidative stress-related parameters under conditions of chronic exposure to high temperatures (HT). From 2 to 6 wk of age, male broiler chickens were reared under either a constant temperature of 32°C until 6 wk of age or a normal temperature scheme (gradual decrease to 18°C at 5 wk of age). Chicks in both the normal and HT treatments were provided with a commercial grower diet supplemented with either 1.0 or 1.2 g/kg of dl-M or 1.0 or 1.2 g/kg of dl-HMTBA. Because there were no effects of supplement dose, data were pooled over both doses within each temperature treatment. The chronic HT treatment impaired feed intake and BW gain, but these negative effects were less pronounced when the chickens received dl-HMTBA. Exposure to HT was also associated with decreased (P < 0.001) plasma thyroid hormones and increased (P < 0.0001) plasma corticosterone levels. At 4 wk of age, and irrespective of the supplemental source, chickens subjected to HT were characterized by significantly lower plasma TBA-reactive substance levels. In contrast, at 6 wk of age, plasma TBA-reactive substance levels were significantly increased by HT, but this effect was observed only for the chickens receiving dl-M and not for those receiving dl-HMTBA. High temperatures induced a significant increase in hepatic total glutathione (GSH) and oxidized GSH levels, regardless of the supplemental source. However, the hepatic ratios of reduced GSH to total GSH and reduced GSH to oxidized GSH were highest in chickens supplemented with dl-HMTBA. In conclusion, dl-HMTBA supplementation partially prevented the growth-depressing effects of chronic heat exposure compared with dl-M supplementation. It can be inferred that dl-HMTBA is more efficient in alleviating HT-induced oxidative damage because of a more favorable reduced GSH-to-total GSH ratio.

Intermittent thermal manipulations of broiler embryos during late incubation and their immediate effect on the embryonic development and hatching process.

Intermittent high (+3°C) and low (-3°C) temperature treatments for 4 h on embryonic day (E) 16, E17, and E18 showed differential effects on embryonic metabolism, without influencing embryonic growth or hatchability. Embryos in the high-temperature group shifted to a more anaerobic metabolism, as indicated by a lower partial pressure of O(2) and a higher partial pressure of CO(2) in the air cell, lower blood pH, and higher lactic acid production. Three hours after the end of the high-temperature treatment, a decrease in metabolism was observed, as indicated by the lower partial pressure of CO(2) and higher partial pressure of O(2) in the air cell and increased plasma triglyceride levels. The embryos in the low-temperature group responded by temporarily slowing down their metabolism, especially the metabolism of carbohydrates and lipids, as indicated by altered air cell gases, a higher relative yolk weight, higher plasma triglyceride level, and higher liver glycogen level. Three hours after the end of the temperature treatment, the metabolism of embryos in the low-temperature treatment had increased to the level of the control temperature group. However, for both temperature treatments, during the hatching process, all the shortages and excesses created were restored to control levels, which would explain the lack of change in embryo growth and hatchability and the slight delay in the hatching process. These mild consequences of the intermittent temperature treatment indicate that the different metabolic shifts made by the embryos seem to be efficient in overcoming the challenges of the intermittent high- or low-temperature treatment during late incubation.

Acid-base regulation during embryonic development in amniotes, with particular reference to birds.

During avian embryonic development, the carbon dioxide tension inside the egg increases as the shell restricts gas exchange with the environment. Acid-base regulation of the avian embryo is a complex process, not only due to the non-function of the lungs and limited functionality of the kidneys but also because the embryo is affected by the inflow of bicarbonates from the shell, when calcium is reabsorbed for calcification. Moreover, interaction occurs between the embryo and the extraembryonic compartments. It has been shown that carbonic anhydrase plays a crucial role in the formation of sub-embryonic fluid and in the chorioallantoic membrane and kidney. This review provides a detailed overview of the acid-base status of the extraembryonic compartments inside chicken eggs, and their interaction in keeping the acid-base status of the embryo balanced. Secondly, experimental acid-base disturbances are summarized. The last part of the review briefly compares embryos of birds and other amniotes (mammals and reptiles) with regard to acid-base regulation.

High- and low-temperature manipulation during late incubation: effects on embryonic development, the hatching process, and metabolism in broilers.

Temperatures continuously higher and lower than the standard incubation temperature by 3°C from embryonic d 16 until embryonic d 18.5 result in differential effects on embryonic development, the hatching process, and embryonic metabolism. Embryos in the high-temperature group were forced into a state of malnutrition by the temperature treatment, as reflected by reduced embryo growth and yolk consumption, resulting in a significantly lower chick weight at hatch. In addition, altered air cell and blood gases as well as a retarded hatching process further indicated reduced growth of embryos exposed to higher incubation temperatures during the latter part of incubation. In addition, hatchability was significantly reduced by the high-temperature treatment due to higher embryonic mortality during the treatment period and the hatching process. Levels of blood glucose, lactate, liver glycogen, plasma triglycerides, and nonesterified fatty acids indicated an altered carbohydrate and lipid metabolism for the high-temperature group. Although the hatching process of embryos exposed to lower incubation temperatures was also significantly retarded, their embryonic development and growth were strikingly similar to those of the control group.

Interaction between ascites susceptibility and CO during the second half of incubation of two broiler lines. Effect on embryonic development and hatching process.

1. Because CO(2) during the second half of incubation is known to influence air cell and blood gases, and embryo development, it is postulated that post-hatch development and ascites sensitivity could also be influenced. 2. An ascites susceptible (A) and an ascites resistant (E) broiler line were incubated under standard incubation or high CO(2) conditions (up to 4%) from embryonic day (ED) 10 onwards. The embryonic development and the hatching process of these two lines were compared when incubated under standard or high CO(2) conditions from over the second half of incubation. 3. The A line, selected for high post-hatch growth rate, exhibited a higher relative embryo weight from ED10 until ED16, which was supported by a higher air cell pCO(2), lower air cell pO(2), higher corticosterone and thyroid hormones and earlier hatching time. 4. Incubation under high CO(2) increased air cell pCO(2), retarded yolk consumption, and decreased glycogen concentration in the liver at hatch. Hatchability decreased in both lines when incubated under high CO(2), due to an increased late mortality of embryos that died before IP. 5. These results suggest that the development and metabolism of CO(2)-incubated embryos differ from control incubated embryos.

The importance of carbonic anhydrase II in red blood cells during exposure of chicken embryos to CO2.

The importance of carbonic anhydrase (CA) during exposure of chicken embryos to CO(2) during the second half of incubation was investigated. The protein abundance and activity of CAII in erythrocytes was significantly higher in CO(2)-exposed embryos compared to normal conditions. Daily injections of acetazolamide (ATZ), an inhibitor of CA, increased blood P(CO2) and decreased blood pH in both control and CO(2)-incubated embryos. ATZ increased blood bicarbonate concentration in embryos exposed to normal atmosphere and in day-12 embryos exposed to high CO(2). The tendency of an increased blood potassium concentration in ATZ-injected embryos under standard atmospheric conditions might indicate that protons were exchanged with intracellular potassium. However, there was no evidence for such an exchange in CO(2)-incubated ATZ-treated embryos. This study shows for the first time that chicken embryos adapt to CO(2) during the second half of incubation by increasing CAII protein expression and function in red blood cells. This response may serve to "buffer" elevated CO(2) levels.

The diagnostic value of soluble CD163 in patients presenting with chest pain.

BACKGROUND: CD163 is a scavenger receptor for the uptake of haptoglobin-hemoglobin (Hpt-Hb) complexes. The Hpt-Hb complexes are being formed in the plaque in response to intraplaque hemorrhage, a hallmark of atherosclerotic plaque instability. We therefore investigated whether soluble CD163 (sCD163) was elevated in patients with an acute coronary syndrome. METHODS: All subjects presenting with chest pain suggestive of myocardial ischemia referred to either the emergency department or the coronary care unit were included in a prospective follow-up study. Plasma was collected and frozen at -80 degrees C until assayed. sCD163 was measured using a commercially available Elisa assay. RESULTS: Of 526 included chest pain patients, the final diagnosis was non-cardiac chest pain in 244 (46%) patients, non-STEMI in 67 (13%), and STEMI in 215 (41%). The non-STEMI patients were older, used more medication, had undergone more often coronary interventions, but did not differ with respect to risk factors, except for a higher incidence in dyslipidemia. Unexpectedly, sCD163 did not differentiate between patients with non-STEMI or STEMI and the non-cardiac chest pain patients (2.09+/-0.76 versus 2.24+/-0.86). CONCLUSION: Although ACS is characterized by intraplaque hemorrhage, the amount of intraplaque Hb release seems not to be substantial enough to result in a measurable difference in sCD163.