Monocrotaline-induced pulmonary hypertension with sufficient tricuspid regurgitation in a rat model

Background and purpose

It is well known that monocrotaline (MCT) induces pulmonary hypertension (PH) in rats. This model is very useful for understanding the physiology of PH and developing treatments for PH. However, it is very difficult to estimate pulmonary artery pressure (PAP) in this model. The purpose of this study is to establish a PH model with sufficient tricuspid regurgitation (TR) to evaluate PAP.

Method

We studied 17 male rats that received 15 injections of 5?mg/kg/day of MCT (PH) or vehicle (control). Three weeks after the first MCT injection, we measured left and right ventricular dimensions, the ratio of acceleration to ejection time in pulmonary flow, and the development of TR using an echocardiograph (SONOS5500) with a s12 probe (frequency: 5–12?MHz, frame rate: 120?Hz).

Results

The right ventricular end-diastolic area in the PH group was significantly larger than that in the control group. The acceleration time/ejection time ratio and velocity time integral of the pulmonary artery in the PH group were smaller than those in the control group. In 78?% of rats in the PH group, sufficient TR was observed and estimated PAP was 75.4?±?13.8?mmHg. There was a good correlation between PAP estimated by a Doppler method and directly measured right ventricular pressure (r?=?0.94, P?<?0.0001).

Conclusion

Fifteen injections of 5?mg/kg/day of MCT could induce PH with sufficient TR in rats. Transthoracic echocardiography could be used for monitoring the progress of PH in the rat model.     

Haemodynamic and neuroendocrine effects of tezosentan in chronic experimental pulmonary hypertension

Purpose

Chronic pulmonary hypertension (PH) therapy is poorly investigated in intensive care. Our aim was to evaluate haemodynamic and neuroendocrine effects of the dual endothelin-1 (ET-1) blocker tezosentan in monocrotaline (MCT)-induced PH.

Methods

Male Wistar rats (180–200?g, n?=?194) randomly received 60?mg?kg^?1 MCT or vehicle, subcutaneously, and 2?days later, a subgroup of MCT-injected rats was gavaged with 300?mg?kg^?1?day^?1 bosentan (MCT BOS, n?=?46), while another (MCT, n?=?125) and control rats (Ctrl, n?=?23) received vehicle. At 25–30?days, 48?h after interrupting bosentan, rats randomly underwent either a dose–response evaluation (0.5–20?mg?kg^?1, n?=?7 each group) or a 4?h perfusion of tezosentan (20?mg?kg^?1 in 10?min?+?10?mg?g^?1?h^?1) or vehicle (n?=?8 per group, each). Haemodynamics, including blood gas analysis, were evaluated after thoracotomy under anaesthesia. After plasma, right ventricle (RV) and lung collection, plasma ET-1, cytokines, nitrate and 6-keto-PGF1α, and lung and right ventricular gene expression and cyclooxygenase (COX) and nitric oxide synthase (NOS) activities were quantified.

Results

Monocrotaline resulted in PH, RV dilation and decreased cardiac output (CO) that were attenuated in MCT BOS. Pulmonary hypertension was attenuated by tezosentan without systemic hypotension. Tezosentan increased CO without changing ventilation-perfusion matching. Both bosentan and tezosentan reduced ET-1 and cytokine plasma levels and tissue expression, and inducible NOS and COX-2 RV activities. Bosentan increased nitrate plasma levels and non inducible NOS activities whereas tezosentan decreased circulating 6-keto-PGF1α but increased lung COX-1 activity.

Conclusions

Tezosentan may be useful for haemodynamic handling and bosentan replacement in critically ill PH patients exerting important beneficial neuroendocrine and anti-inflammatory actions.     

The value of speckle-tracking echocardiography in identifying right heart dysfunction in patients with chronic thromboembolic pulmonary hypertension

Right ventricular (RV) function is a significantly important factor in the determination of the prognosis of chronic thromboembolic pulmonary hypertension (CTEPH) patients. Speckle-tracking echocardiography (STE) is an angle-independent new technique for quantifying myocardial deformation that is capable of providing data on multiple parameters including longitudinal and transverse information of the myocardium. In the present study, we aimed to study the advantages of STE-derived parameters in identifying RV dysfunction in CTEPH patients. Sixty CTEPH patients (mean age: 55 years?±?13 years; 25 males) and 30 normal controls (mean age: 54 years?±?14 years; 14 males) were enrolled in this study. RV free wall (RVFW) systolic peak longitudinal strain (LS) including the basal, mid-, and apical-segments and the basal longitudinal and transverse displacement (basal-DL and basal-DT) were measured by STE. Global LS (GLS) of the RV was calculated by averaging the LS value of the 3 segments of RVFW. Clinical data of CTEPH patients were collected. CTEPH patients were divided into 2 subgroups according to the World Health Organization function classification. Clinical right heart failure (RHF) was defined as the presence of symptoms of heart failure and signs of systemic circulation congestion during hospitalization. The apical segment LS of the RVFW was lower than that in the basal and mid-segments in the control group (P?<?0.001), but no significant difference was found among the 3 segments of LS in the CTEPH group (P?=?0.263). When we used the cutoff value recommended by the American Society of Echocardiography guidelines to identify abnormal RV function, 30 CTEPH patients (50%) by tricuspid annular plane systolic excursion (TAPSE), 42 patients (70%) by fractional area change (FAC), 20 patients (33.33%) by RV index of myocardial performance (RVIMP), and 46 patients (77%) patients by GLS were determined to have abnormal RV function, respectively. Among multiple RV function indicators, TAPSE, FAC, GLS, basal-DL, and N-terminal pronatriuretic B-type natriuretic peptide showed significant differences between CTEPH patients with mild (WHO II) and severe symptoms (WHO III/IV) (all P?<?0.001), while RVIMP and basal-DT showed no significant difference (P?=?0.188 and P?=?0.394, respectively). Pearson correlation analysis showed that GLS has no correlation with sPAP as evaluated by echocardiography in CTEPH patients (r = ??0.079, P?=?0.574), and a weak to moderate correlation with RA area (r?=?0.488, P?=?0.000), the RV diameter (r?=?0.429, P?=?0.001), and the RVFW thickness (r?=?0.344, P?=?0.009). On receiver operating characteristic analysis, GLS has the largest area under the curve to identify RHF when the cutoff value was ??13.45%, the sensitivity was 78.2%, and the specificity was 84.6%, separately. Our study demonstrated that the depression of regional LS of RVFW is more pronounced in the basal and middle segments in CTEPH patients. Also, the longitudinal movement is much more important than the transverse movement when evaluating RV systolic function. As compared with conventional parameters, RVFW GLS showed more sensitivity to identify abnormal RV function and had the largest AUC for identifying RHF. Additionally, GLS showed no correlation with sPAP and a weak correlation with right heart morphological parameters in our CTEPH cohort.     

Arctigenin prevents monocrotaline-induced pulmonary arterial hypertension in rats

The hallmark features of the development of pulmonary arterial hypertension (PAH) include the proliferation of pulmonary vascular smooth muscle cells, oxidative stress, inflammation, and pulmonary artery remodeling. Arctigenin is a bioactive component of Arctium lappa that exerts anti-inflammatory and antiproliferative effects in several diseases; however, its effects on pulmonary arteries are still unclear. This study aimed to investigate the efficacy of arctigenin to prevent PAH. Rats injected with monocrotaline (MCT) progressively developed PAH. Arctigenin treatment (50 mg per kg per day, intra-peritoneally) ameliorated right ventricular systolic pressure and pulmonary arterial remodeling, decreased the expression of inflammatory cytokines, and limited the proliferation of pulmonary vascular smooth muscle cells in lungs. Mechanistically, arctigenin effectively inhibited the MCT-induced elevation of NLRP3, caspase-1, and interleukin 1-beta expression in the lungs. These results indicate that arctigenin ameliorates MCT-induced PAH, at least in part, through exerting its anti-inflammatory, antioxidant, and antiproliferative effects, which inhibit the NLRP3 inflammasome signal pathway in rats.

Arctigenin ameliorates monocrotaline-induced pulmonary arterial hypertension, at least in part, through exerting its anti-inflammatory, antioxidant, and antiproliferative effects, which inhibit the NLRP3 inflammasome signal pathway in rats.     

Ang-（1-7）与肺高压状态下肺血管平滑肌细胞的增生

背景：Ang-（1-7）虽然具有抗血管平滑肌细胞增殖作用,但在不同的血管床中其作用可能存在差异。直接给予外源性Ang-（1-7）是否可抑制肺动脉高压大鼠肺血管平滑肌细胞的增殖尚不清楚。目的：探讨Ang-（1-7）对野百合碱诱导的肺动脉高压大鼠肺血管平滑肌细胞增殖的影响。方法：雄性SD大鼠颈部一次性注射60mg／kg野百合碱制备肺动脉高压模型。24h后,分别经微泵持续泵入Ang-（1-7）（治疗组）或生理盐水（模型组）,并设立未造模的对照组。给药2,4周,测定大鼠的右心室收缩压、心室质量、肺小动脉管壁厚度占管径的百分比及管壁面积占血管总面积的百分比。免疫组织化学方法检测肺血管平滑肌细胞a一平滑肌肌动蛋白及增殖细胞核抗原的表达。结果与结论：野百合碱诱导2周。与对照组比较,模型组大鼠右心室收缩压、各心室的质量无明显变化,肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率显著增高,a一平滑肌肌动蛋向娃著降低：野百合碱诱导4周,模型组大鼠右心室收缩压、各心室的质量、肺小动脉管壁厚度占管径的百分比、管壁面积占血管总面积的百分比、增殖细胞核抗原阳性率均显著增高,a一平滑肌肌动蛋白最著降低。而治疗组上述指标与对照组比较差异无锃著性意义（P〉0.05）。说明在野百合碱诱导的肺动脉高压模型中,在肺动脉压增高之前已有肺血符形态学的变化,Ang-（1-7）可通过减轻肺血管平滑肌细胞的增生抑制大鼠肺动脉压的升高。     

Step climbing capacity in patients with pulmonary hypertension

Background

Patients with pulmonary hypertension (PH) typically have exercise intolerance and limitation in climbing steps.

Objectives

To explore the exercise physiology of step climbing in PH patients, on a laboratory-based step test.

Methods

We built a step oximetry system from an ‘aerobics’ step equipped with pressure sensors and pulse oximeter linked to a computer. Subjects mounted and dismounted from the step until their maximal exercise capacity or 200 steps was achieved. Step-count, SpO₂ and heart rate were monitored throughout exercise and recovery. We derived indices of exercise performance, desaturation and heart rate. A 6-min walk test and serum NT-proBrain Natriuretic Peptide (BNP) level were measured. Lung function tests and hemodynamic parameters were extracted from the medical record.

Results

Eighty-six subjects [52 pulmonary arterial hypertension (PAH), 14 chronic thromboembolic PH (CTEPH), 20 controls] were recruited. Exercise performance (climbing time, height gained, velocity, energy expenditure, work-rate and climbing index) on the step test was significantly worse with PH and/or worsening WHO functional class (ANOVA, p < 0.001). There was a good correlation between exercise performance on the step and 6-min walking distance–climb index (r = ?0.77, p < 0.0001). The saturation deviation (mean of SpO₂ values <95 %) on the step test correlated with diffusion capacity of the lung (ρ = ?0.49, p = 0.001). No correlations were found between the step test indices and other lung function tests, hemodynamic parameters or NT-proBNP levels.

Conclusions

Patients with PAH/CTEPH have significant limitation in step climbing ability that correlates with functional class and 6-min walking distance. This is a significant impediment to their daily activities.     

Non-invasive quantification of right ventricular systolic function by echocardiography: a new semi-automated approach

Background

Right ventricular (RV) function determines long-term outcome in many cardiopulmonary diseases. However, the assessment of RV function is time-consuming and surrogate parameters derived from two-dimensional (2D) or Doppler echocardiography show poor consistency.

Methods

Forty consecutive patients were examined within 30 min after magnetic resonance imaging (MRI) with comprehensive echocardiography, including strain imaging and real-time three-dimensional echocardiography. A new parameter, the RV automated systolic index (RV-ASI), was obtained from the apical four-chamber view using semi-automated border detection.

Results

RV-ASI could be assessed by 2D echocardiography in 38 of 40 patients. RV ejection fraction assessed by MRI was 48 ± 9 %, while RV-ASI was 52 ± 11 % (r = 0.74, SEE = 6 %, p < 0.0001). Intra- and inter-observer variabilities were 7.5 and 8.9 %, respectively. An RV-ASI cut-off value of 52 % in this cohort was able to differentiate between normal and impaired RV function (AUC 0.92, sensitivity 87 %, specificity 93 %).

Conclusions

In this study, the RV-ASI showed to be an easy, rapid to assess and reliable tool for quantification of right ventricular function. Furthermore, this index can complement the assessment of right ventricular mechanics by 2D strain imaging for efficient and comprehensive non-invasive evaluation of right ventricular function.     

Unrecognized secondary causes of hypertension in patients with hypertensive urgency/emergency: prevalence and co-prevalence

Background

Hypertensive urgency/emergency occurs frequently, yet no prospective data on common secondary causes, including sleep apnea (SA), renal artery stenosis (RAS), and hyperaldosteronism, are available.

Methods

Patients presenting to the emergency room for over 1 year with systolic blood pressure ≥180 mmHg and/or diastolic blood pressure ≥100 mmHg and typical symptoms were included. RAS was diagnosed by direct duplex/Doppler ultrasound of the renal artery, resistance index, and imaging. The aldosterone/renin ratio (ARR) was determined from morning blood samples taken with the patients supine after ≥2 h of rest. A positive ARR (>50) was followed by saline infusion to exclude primary hyperaldosteronism. SA was evaluated by nasal breathing flow screening; when positive [apnea/hypopnea index (AHI) >5/h], complete polysomnography was performed.

Results

Of 161 patients (age, 66.0 ± 13.1 years; BMI, 28.6 ± 5.1 kg), 131 had previously identified hypertension (duration, 12.7 ± 11.5 years; 1.9 ± 1.5 antihypertensive medications). SA was found in 114 (70.8%) patients [18% mild (AHI: 5–15/h), 26.8% moderate (15.1–30/h), and 24.2% severe (>30/h)]. Aldosterone levels exceeded 160 pg/ml in 22 of 23 patients with hyperaldosteronism; 4 had primary and 12 had secondary hyperaldosteronism. Thirteen (8.1%) patients had RAS. Three secondary causes were found in 1 patient (0.6%), ≥2 in 25 (15.5%), and ≥1 in 124 patients (77.0%). Of 150 detected secondary causes, only 5 were recognized previously.

Conclusions

Secondary causes of hypertension are common and predominantly unrecognized in patients with hypertensive urgency/emergency. Co-prevalence of secondary causes occurs in about 15% and should be considered before therapeutic intervention.     

Dimeric [68Ga]DOTA-RGD Peptide Targeting αvβ3 Integrin Reveals Extracellular Matrix Alterations after Myocardial Infarction

Purpose

We evaluated a dimeric RGD-peptide, [⁶⁸Ga]DOTA-E-[c(RGDfK)]₂, for positron emission tomography (PET) imaging of myocardial integrin expression associated with extracellular matrix remodeling after myocardial infarction (MI) in rat.

Procedures

Male Sprague-Dawley rats were studied at 7 days and 4 weeks after MI induced by permanent ligation of the left coronary artery and compared with sham-operated controls.

Results

In vivo imaging revealed higher tracer uptake in the infarcted area than in the remote non-infarcted myocardium of the same rats both at 7 days (MI/remote ratio, 2.25?±?0.24) and 4 weeks (MI/remote ratio, 2.13?±?0.37) post-MI. Compared with sham-operated rats, tracer uptake was higher also in the remote, non-infarcted myocardium of MI rats both at 7 days and 4 weeks where it coincided with an increased interstitial fibrosis. Standardized uptake values correlated well with the results of tracer kinetic modeling. Autoradiography confirmed the imaging results showing 5.1 times higher tracer uptake in the infarcted than remote area. Tracer uptake correlated with the amount of β₃ integrin subunits in the infarcted area.

Conclusions

Our results show that integrin-targeting [⁶⁸Ga]DOTA-E-[c(RGDfK)]₂ is a potential tracer for monitoring of myocardial extracellular matrix remodeling after MI using PET.     

Renal sympathetic denervation therapy in the real world: results from the Heidelberg registry

Introduction

Renal sympathetic denervation (RDN) is a novel treatment option in patients with treatment-resistant arterial hypertension. A subset of recently published randomized and non-randomized trials indicates that RDN leads to sustained lowering of blood pressure (BP) under controlled study conditions. However, registry data that allow evaluation of safety and efficacy in a real-world setting are largely missing.

Methods

Sixty-three consecutive patients with treatment-resistant hypertension underwent RDN with the radiofrequency-based Symplicity? catheter. As part of our prospective registry, treatment efficacy and safety were monitored after 3, 6, and 12 months.

Results

At 6 months follow-up, office systolic BP significantly improved by 19 + 23 mmHg as compared to baseline, while diastolic BP values reduced by 6 + 13 mmHg (p < 0.05). One year after RDN, office BP levels further improved (26 + 25 mmHg in systolic BP and 9 + 13 mmHg in diastolic BP, respectively), even though 19 patients had reduced the number and/or dosage of antihypertensive agents. The response rate, defined as reduction of office systolic BP of ≥10 mmHg, was 73 % after 6 months. Baseline BP was the only significant predictor of blood pressure response, whereas no correlation was found between the number of ablation points and the individual changes in office blood pressure. Interestingly, patients with challenging renal anatomy profited somewhat less from the procedure than those with “normal” renal anatomy. Procedure related adverse events occurred in three patients (4.7 %) and were limited to vascular access complications.

Conclusions

RDN with the Symplicity? system is safe and effective in patients with treatment-resistant hypertension also in a real-world setting.     

Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial

Purpose

Preventive treatments of traumatic intracranial hypertension are not yet established. We aimed to compare the efficiency of half-molar sodium lactate (SL) versus saline serum solutions in preventing episodes of raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).

Methods

This was a double-blind, randomized controlled trial including 60 patients with severe TBI requiring ICP monitoring. Patients were randomly allocated to receive a 48-h continuous infusion at 0.5 ml/kg/h of either SL (SL group) or isotonic saline solution (control group) within the first 12 h post-trauma. Serial measurements of ICP, as well as fluid, sodium, and chloride balance were performed over the 48-h study period. The primary outcome was the number of raised ICP (≥20 mmHg) requiring a specific treatment.

Results

Raised ICP episodes were reduced in the SL group as compared to the control group within the 48-h study period: 23 versus 53 episodes, respectively (p < 0.05). The proportion of patients presenting raised ICP episodes was smaller in the SL group than in the saline group: 11 (36 %) versus 20 patients (66 %) (p < 0.05). Cumulative 48-h fluid and chloride balances were reduced in the SL group compared to the control group (both p < 0.01).

Conclusion

A 48-h infusion of SL decreased the occurrence of raised ICP episodes in patients with severe TBI, while reducing fluid and chloride balances. These findings suggest that SL solution could be considered as an alternative treatment to prevent raised ICP following severe TBI.     

Effects of selective and unselective endothelin-receptor antagonists on prostacyclin synthase gene expression in experimental pulmonary hypertension

OBJECTIVE: Compared to the unselective endothelin (ET) receptor antagonist (Bosentan), superior effects of selective ET-A-receptor blockage (Ambrisentan) for the treatment of pulmonary hypertension (PH) are expected due to ET-B-receptor mediated beneficial effects. Our hypothesis was that treatment with Ambrisentan leads to an increase in prostacyclin synthase I (PGIS) expression compared to Bosentan. MATERIAL AND METHODS: To test this hypothesis, rats were treated with either monocrotaline (MCT) only, MCT+Ambrisentan or MCT+Bosentan. After 4 weeks, right ventricular systolic pressure (RVSP), pulmonary vascular remodelling and right ventricular hypertrophy (RV/(LV+S)) were measured. RESULTS: In MCT only treated animals, significantly greater expression of PGIS mRNA was found in the lungs compared to control animals, and this was confirmed by immunohistochemical analysis indicating increased staining of PGIS in the very small pulmonary arteries (17 % greater expression of PGIS mRNA in MCT versus control, p = 0.002; Remmele score (RS): 51 versus 102, p = 0.009). Treatment with Bosentan resulted in a significantly lower expression of PGIS mRNA compared to Ambrisentan and MCT only (7 % versus 18 %, p = 0.003 and 7 % versus 17 %, p = 0.004). This observation was also confirmed by immunohistochemical analysis (RS very small arteries: 45 versus 81, p = 0.003; RS small arteries: 45 versus 108, p = 0.014). No difference was observed in RVSP, RV/(LV+S) or pulmonary vascular remodelling between the two treatment groups (RVSP: 28 versus 39 mmHg, p = 0.189; RV/(LV+S) 0.46 versus 0.48, p = 0.818; medial area: 78.3 % versus 75.2 %, p = 0.823). CONCLUSIONS: Treatment with Bosentan leads to lower PGIS expression in pulmonary arteries compared to Ambrisentan, although the greater PGIS expression by Ambrisentan treatment had no benefical effect on pulmonary haemodynamics.     

白介素4通过调节巨噬细胞分化促进野百合碱诱导大鼠肺动脉高压模型的肺血管重塑

目的探讨大鼠肺动脉高压模型中白介素-4(IL-4)对巨噬细胞分化和肺血管重塑的影响。方法利用野百合碱(MCT)腹腔注射构建大鼠肺动脉高压模型,以超声心动图及病理改变作为建模成功的观察指标。采用Elisa及荧光定量PCR(qRT-PCR)检测各组血液中IL-4的表达。利用IL-4中和抗体静脉注射肺动脉高压大鼠,抑制体内IL-4的作用,并通过超声心动图及HE染色观察肺动脉高压情况。结果与对照组比较,肺动脉高压组大鼠血液中IL-4的表达(4.01±0.18 vs.9.08±0.25)明显上调(P0.01),大鼠右心室压力(58.00±2.84 vs.20.13±1.89)明显上调(P0.01),且肺血管重塑明显增加。与肺动脉高压组和IgG组比较,IL-4中和抗体组大鼠右心室压力[(42.77±2.04)vs.(58.00±2.84)vs.(57.62±1.44)]明显降低(P0.01),且肺血管重塑明显降低。与肺动脉高压组和IgG组比较,IL-4中和抗体组大鼠肺组织中CD206mRNA表达量[(2.88±0.17)×10-3vs.(4.22±0.08)×10-3vs.(4.36±0.26)×10-3]明显降低(P0.01)。结论肺动脉高压后,上调的IL-4可以促进巨噬细胞向Ⅱ型巨噬细胞分化,进而调节肺动脉的血管重塑过程。     

Assessment of pulmonary arterial stiffness in obstructive sleep apnea

Pulmonary hypertension (PH) is one of the major complications of obstructive sleep apnea syndrome (OSAS). Pulmonary arterial stiffness (PAS) can be used in determination of PH. The aim of the present study was to evaluate the PAS and cardiac function of patients with OSAS and analyses the relationship between OSAS severity and PAS. Sixty newly diagnosed patients with OSAS (mean age 49.6 ± 11.7 years) and 30 healthy controls (mean age 46.4 ± 14 years) were enrolled. Right ventricle (RV) and left ventricle (LV) echocardiographic parameters and PAS values of study groups were compared. There were no significant differences in terms of LV ejection fraction, LV Tei-index and tricuspid annular plane systolic excursion. PAS, mean pulmonary arterial pressure (PAP) and RV Tei-index were significantly higher but tricuspid annulus early diastolic myocardial velocity was lower in patients with OSAS than control subjects (respectively p < 0.001, p < 0.001, p = 0.001, p = 0.001). Moreover, we found a higher PAS in OSAS patients without PH compared to controls (p < 0.001). When we investigated the relationship between polysomnographic variables and echocardiographic parameters, we found positive correlations between apnea hypopnea index and total oxygen desaturation with PAS and mean PAP (r = 0.384, p < 0.001; r = 0.404, p < 0.001; r = 0.36, p < 0.001; r = 0.349, p = 0.001 respectively). PAS and mean PAP were increased in patients with OSAS. Pulmonary vascular bed may be affected due to the fluctuation of PAP during day and night time. Therefore, assessment of PAS can be more useful than PAP in OSAS patients.     

Gastric residual volume during enteral nutrition in ICU patients: the REGANE study

Objective

To compare the effects of increasing the limit for gastric residual volume (GRV) in the adequacy of enteral nutrition. Frequency of gastrointestinal complications and outcome variables were secondary goals.

Design

An open, prospective, randomized study.

Setting

Twenty-eight intensive care units in Spain.

Patients

Three hundred twenty-nine intubated and mechanically ventilated adult patients with enteral nutrition (EN).

Interventions

EN was administered by nasogastric tube. A protocol for management of EN-related gastrointestinal complications was used. Patients were randomized to be included in a control (GRV = 200 ml) or in study group (GRV = 500 ml).

Measurements and results

Diet volume ratio (diet received/diet prescribed), incidence of gastrointestinal complications, ICU-acquired pneumonia, days on mechanical ventilation and ICU length of stay were the study variables. Gastrointestinal complications were higher in the control group (63.6 vs. 47.8%, P = 0.004), but the only difference was in the frequency of high GRV (42.4 vs. 26.8%, P = 0.003). The diet volume ratio was higher for the study group only during the 1st week (84.48 vs. 88.20%) (P = 0.0002). Volume ratio was similar for both groups in weeks 3 and 4. Duration of mechanical ventilation, ICU length of stay or frequency of pneumonia were similar.

Conclusions

Diet volume ratio of mechanically ventilated patients treated with enteral nutrition is not affected by increasing the limit in GRV. A limit of 500 ml is not associated with adverse effects in gastrointestinal complications or in outcome variables. A value of 500 ml can be equally recommended as a normal limit for GRV.     

Haltungsasymmetrie bei Säuglingen und deren osteopathische Behandlung

Purpose

To assess the therapeutic efficacy of osteopathic treatment in infants with postural asymmetry.

Patients and methods

A randomized clinical trial of efficacy with blinded videoscoring was performed. Sixty-one infants with postural asymmetry aged 6–12 weeks (median: 9) were recruited. Thirty-two infants (18 male, 14 female) with a gestational age ≥36 weeks were found to be eligible and randomly assigned to the intervention groups; 16 received osteopathic treatment and 16 sham therapy. After a treatment period of 4 weeks the outcome was measured using a standardised scale (40–24 points).

Results

With sham therapy, five infants improved (=3 points), eight infants were unchanged (±<3 points) and three infants deteriorated (>?3 points); the mean improvement was 1.2 points (SD±3.5). In the osteopathic group 13 infants improved and 3 remained unchanged; the mean improvement was 5.9 points (SD±3.8). The difference was significant (p=0.001).

Conclusion

Osteopathic treatment in the first months of life improves the degree of asymmetry in infants with postural asymmetry.     

Natriuretic peptides in the detection of preclinical diastolic or systolic dysfunction

Aims

The diagnostic value of natriuretic peptides in asymptomatic patients at risk for diastolic or systolic HF is controversial. We tested (1) the prevalence of preclinical LV dysfunction in an at-risk cohort; (2) the diagnostic accuracy of natriuretic peptides alone or in combination with clinical parameters for predicting asymptomatic left ventricular systolic or diastolic dysfunction.

Methods

542 primary care patients (mean age 63 ± 11 years, 42% female) without prediagnosed HF, but with risk factors for left ventricular dysfunction, underwent thorough cardiological workup, including echocardiography and analysis of natriuretic peptides.

Results

23 patients (4%) showed reduced systolic function (EF < 50%), and 15 patients (3%) had severe diastolic dysfunction. All natriuretic peptides significantly increased with decreasing ejection fraction and with increasing degree of diastolic dysfunction. For natriuretic peptides, receiver operating characteristics analysis yielded good results for the detection of systolic dysfunction or severe diastolic dysfunction. Combining clinical parameters with natriuretic peptide data improved the diagnostic accuracy and largely reduced the number of needed screening echoes to identify patients with LV systolic or diastolic dysfunction.

Conclusions

The prevalence of preclinical diastolic dysfunction is high in primary care patients at risk, but the relative prevalence of severe diastolic dysfunction and systolic dysfunction is only 7%. High-risk individuals may be screened most efficiently by using a score system incorporating clinical data and NT-proBNP.     

Exaggerated increase of exercise-induced pulmonary artery pressure in systemic sclerosis patients predominantly results from left ventricular diastolic dysfunction

Objective

High prevalence of exaggerated pulmonary artery pressure response to exercise (EPAPR) was reported in patients with systemic sclerosis (SSc). However, pathophysiology of this phenomenon has not been well defined. Therefore, we evaluated the frequency and potential aetiology of EPAPR in SSc patients.

Methods

We included 85 patients (79 female, 6 male, mean age 54.3 ± 13.9 years) with SSc. Transthoracic echocardiography followed by exercise Doppler echocardiography (EDE) were performed. A positive EDE was defined when at least 20 mmHg increase of tricuspid regurgitation peak gradient (TRPG) was recorded. Right heart catheterization (RHC) with exercise was performed in positive EDE patients and in subjects with resting TRPG >31 mmHg.

Results

Resting TRPG >31 mmHg and/or positive EDE was found in 30 patients and they were referred to RHC. Finally, RHC was performed in 20 patients (16 pts resting TRPG >31 mmHg and 4 others normal resting TRPG and positive EDE). In 12 (60 %) of them an EPAPR with elevated pulmonary capillary wedge pressure (PCWP) was observed. Interestingly, mean left atrium (LA) diameter was greater in an EPAPR with elevated PCWP patients than in subjects with normal exercise response (39.36 ± 5.6 vs. 35.53 ± 3.48, p = 0.03). In EPAPR with elevated PCWP group greater mean value of E/E′ of mitral lateral annulus was observed (7.98 ± 3.35 vs. 6.27 ± 1.94, p = 0.03). In the univariate logistic regression analysis increased LA diameter was significant predictor of EPAPR with elevated PCWP (OR 1.199, 95 % CI 1.029–1.396, p = 0.019).

Conclusions

Despite very well-known risk of PAH in systemic sclerosis patients, the excessive increase of PAP during exercise is more commonly caused by left ventricular diastolic dysfunction than pulmonary arterial vasculopathy.     

Safety and effects of two red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial

Objective

To investigate the safety and effects of a restrictive red blood cell (RBC) transfusion strategy in pediatric cardiac surgery patients.

Design

Randomized controlled trial.

Setting

Pediatric ICU in an academic tertiary care center, Leiden University Medical Center, Leiden, The Netherlands.

Patients

One hundred seven patients with non-cyanotic congenital heart defects between 6 weeks and 6 years of age. One hundred three patients underwent corrective surgery on cardiopulmonary bypass.

Interventions

Prior to surgery patients were randomly assigned to one of two groups with specific RBC transfusion thresholds: Hb 10.8 g/dl (6.8 mmol/l) and Hb 8.0 g/dl (5.0 mmol/l).

Measurements

Length of stay in hospital (primary outcome), length of stay in PICU, duration of ventilation (secondary outcome), incidence of adverse events and complications related to randomization (intention to treat analysis).

Results

In the restrictive transfusion group, mean volume of transfused RBC was 186 (±70) ml per patient and in the liberal transfusion group 258 (±87) ml per patient, (95 % CI 40.6–104.6), p < 0.001. Length of hospital stay was shorter in patients with a restrictive RBC transfusion strategy: median 8 (IQR 7–11) vs. 9 (IQR 7–14) days, p = 0.047. All other outcome measures and incidence of adverse effects were equal in both RBC transfusion groups. Cost of blood products for the liberal transfusion group was 438.35 (±203.39) vs. 316.27 (±189.96) euros (95 % CI 46.61–197.51) per patient in the restrictive transfusion group, p = 0.002.

Conclusions

For patients with a non-cyanotic congenital heart defect undergoing elective cardiac surgery, a restrictive RBC transfusion policy (threshold of Hb 8.0 g/dl) during the entire perioperative period is safe, leads to a shorter hospital stay and is less expensive.     

Effect of bosentan therapy on ventricular and atrial function in adults with Eisenmenger syndrome. A prospective,multicenter study using conventional and Speckle tracking echocardiography

Background

The effect of bosentan on the ventricular and atrial performance in patients with Eisenmenger syndrome is unclear. In adult patients with Eisenmenger syndrome, we aimed to evaluate the midterm effect of bosentan on physical exercise, ventricular and atrial function, and pulmonary hemodynamics.

Methods

Forty adult patients before and after 24 weeks bosentan therapy underwent 6 min walk test, two-dimensional speckle tracking echocardiography, plasma NT-proBNP measurement and cardiac catheterization.

Results

After 24 weeks, bosentan therapy an improvement was observed regarding the 6 min walk distance from a median (quartile 1–quartile 3) of 382.5 (312–430) to 450 (390–510) m (p = 0.0001), NT-proBNP from 527.5 (201–1,691.25) to 369 (179–1,246) pg/ml (p = 0.021), right ventricular mean longitudinal systolic strain from 18 (13–22) to 19 (14.5–25) % (p = 0.004), left ventricular mean longitudinal systolic strain from 16 (12–21) to 17 (16–22) % (p = 0.001), right atrial mean peak longitudinal strain from 26 (18–34) to 28 (22–34) % (p = 0.01) and right atrial mean peak contraction strain from 11 (8–16) to 13 (11–16) % (p = 0.005). The invasively obtained Qp:Qs and Rp:Rs did not significantly change under bosentan therapy.

Conclusions

In adult patients with Eisenmenger syndrome, bosentan therapy improves ventricular and atrial functions resulting in enhancement of physical exercise and reduction in the NT-proBNP level, while the pulmonary vascular resistance does not change substantially.