Inspiratory Muscle Training Strategies in Tracheostomized Critically Ill Individuals.

BACKGROUND: Inspiratory muscle training (IMT) strategies can reduce ICU length of stay and optimize recovery in critically ill patients. Our objective was to compare IMT combined with spontaneous breathing with T-piece in tracheostomized subjects. METHODS: Tracheostomized critically ill subjects who were ready to wean were selected and randomly allocated to one of 2 groups: electronically-assisted IMT (EIMT) or spontaneous breathing with T-piece. Electronically assisted IMT was delivered using 30% of maximal inspiratory pressure (manual EIMT or automatically adjusted loads). The following variables were analyzed: ICU length of stay, weaning time, maximal inspiratory pressure, rapid shallow breathing index, pressure (cm H2O), power (W), flow (L/s), volume (L), and energy (J). RESULTS: A total of 132 patients were assessed; 104 subjects were enrolled with EIMT, n = 51 (automatic EIMT, n = 25 and manual EIMT n = 26), or spontaneous breathing with T-piece group, n = 53. The Acute Physiology and Chronic Health Evaluation II score was significantly higher (P = .02) in subjects in the manual EIMT group. Weaning time did not differ significantly between groups (8.55 ± 6.48 d and 10.86 ± 6.48 d, EIMT and spontaneous breathing with T-piece group, respectively; P = .23). Weaning success rates (75%) were lower in the manual EIMT group. Invasive mechanical ventilation time was longer but not significantly different (P = .21) in the spontaneous breathing with T-piece group. Maximal inspiratory pressure was significantly higher in the spontaneous breathing with T-piece and the automatic EIMT groups (P < .001 and P = .007, respectively). Pressure, power, and energy values were significantly higher in the manual EIMT group (P < .001, P = .003, and P = .003, respectively). CONCLUSIONS: IMT modalities in this trial had no significant impacts on weaning time or successful weaning rates.

P-wave duration is a predictor for long-term mortality in post-CABG patients.

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05-1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients.

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

Correction: Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.

[This corrects the article DOI: 10.1371/journal.pone.0166845.].

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.

PURPOSE: Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. METHODS: Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. RESULTS: End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. CONCLUSION: Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.

Diacerein improves left ventricular remodeling and cardiac function by reducing the inflammatory response after myocardial infarction.

BACKGROUND: The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo. METHODS AND RESULTS: Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription. CONCLUSIONS: Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway.

Use of a novel polyvinyl alcohol membrane as a pericardial substitute reduces adhesion formation and inflammatory response after cardiac reoperation.

BACKGROUND: Adhesions may increase the incidence of lethal complications of cardiac reoperations, which account for up to 20% of all open-heart surgeries. Herein, we describe the use of a polyvinyl alcohol membrane (PVAM) as a pericardial alternative and describe its performance during reoperation in a relevant animal model. METHODS: The PVAM samples were reticulated by electron beam radiation and manipulated into a tube shape. After thoracotomy, the pericardium of Wistar rats was opened to expose the heart. Rats were treated by pushing the heart back into the thoracic cavity (Sham group), sprinkling the epicardium with talcum powder (Talc group), encircling the heart with PVAM (PVAM group), or sprinkling the epicardium with talcum powder before placing the PVAM to encircle the heart (PVAM + Talc group). Animals were recovered for 8 weeks and then euthanized. Macroscopic findings (ie, extent and severity of adhesions) were classified according to a 4-grade adhesion scale. The PVAM was tested for direct and indirect cytotoxicity with Vero cells. The water absorption capability and in vivo calcification after 8 weeks of subcutaneous implantation of the membrane were examined. Data were analyzed by analysis of variance and Bonferroni post hoc tests. RESULTS: The PVAM group had lower adhesion scores than the Talc and Sham groups, as well as reduced epicardium thickness and inflammatory cell results, compared with the Talc and PVAM + Talc groups. The PVAM exhibited no direct or indirect cytotoxicity, good water absorption capability (42.4% ± 0.9%), and negligible calcification after 8 weeks (4.42 × 10(-3) ± 2.56 × 10(-3) percentage of the total mass). CONCLUSIONS: The PVAM shows promising properties for its potential use as a novel pericardial substitute.

Ventricular pacing threshold after transthoracic external defibrillation with two different waveforms: an experimental study.

AIMS: Although an increase in the ventricular pacing threshold (VPT) has been observed after administration of transthoracic shock for ventricular defibrillation, few studies have evaluated the phenomenon with respect to the defibrillation waveform energy. Therefore, this study examined the VPT behaviour after transthoracic shock with a monophasic or biphasic energy waveform. METHOD AND RESULTS: Domestic Landrace male piglets implanted with a permanent pacemaker stimulation system were divided into three groups: no ventricular fibrillation (VF) induction and transthoracic shock with monophasic or biphasic energy (group I); VF induction, 1 min of observation without intervention, 2 min of external cardiac massage, and transthoracic shock with monophasic or biphasic energy (group II); and VF induction, 2 min of observation without intervention, 4 min of external cardiac massage, and transthoracic shock with monophasic or biphasic energy (group III). After external shock, the VPT was evaluated every minute for 10 min. A total of 143 experiments were performed. At the end of the observation period, groups I and II showed steady VPT values. Group III showed an increase in VPT with monophasic or biphasic external energy, with no difference between the external energy sources. The monophasic but not the biphasic waveform was associated with higher VPT values when the VF was longer. CONCLUSION: Defibrillation does not have a significant impact on pacing threshold, but a longer VF period is related to a higher VPT after defibrillation with monophasic waveform.

Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury.

OBJECTIVES: The effect of erythropoietin (EPO) on neonatal hearts is not well understood. The current hypothesis is that EPO has protective effects against ischaemia-reperfusion when administered prior to ischaemia induction. METHODS: Systolic and diastolic indices, as well as the Akt and extracellular-regulated kinase (Erk) signalling pathways, were studied in vivo using a neonatal pig heart model. Regional ischaemia was induced for 45 min by the ligation of the left anterior descending artery, followed by 90 min of reperfusion. The treatment groups consisted of: (i) untreated controls, (ii) treatment with EPO 3 min prior to ischaemia and (iii) treatment with EPO 24 h before ischaemia. Sophisticated myocardial contractility indices were assessed by pressure/volume loops of the left ventricle. The Akt and Erk pathways were evaluated via a western blot. RESULTS: Elastance was found to be higher in the group receiving EPO 3 min prior to ischaemia. In addition, preload recruitable stroke work was higher for both groups receiving EPO prior to ischaemia when compared with controls. The time constant of the isovolumic relaxation and end-diastolic pressure-volume relationship did not differ between the three groups after 90 min of reperfusion. Furthermore, EPO treatment enhanced phosphorylation of Akt, but not Erk, and EPO-treated animals showed lower levels of apoptosis-related proteins. CONCLUSIONS: EPO had a protective effect on neonatal systolic function after ischaemia/reperfusion injury, but no effect on diastolic function. This cardioprotective effect might be mediated by the activation of the Akt pathway.

Six-minute walk test as a tool for assessing the quality of life in patients undergoing coronary artery bypass grafting surgery.

OBJECTIVE: To assess the quality of life in patients undergoing myocardial revascularization using the six-minute walk test. METHODS: Prospective observational study with patients who undergoing CABG. The clinical variables, the sixminute walk test, and the SF-36 test were recorded. The patients were assessed at the preoperative time and at 2 months of postoperative period. According their six-minute walk test results, the patients were divided into two groups: group walked more than 350 meters (> 350 meters Group) and the group walked less than 350 meters (< 350 meters Group) at the preoperative time. RESULTS: Eight-seven patients were included. Age was comparable in both groups (59 ± 9.5 years vs. 61 ± 9.3 years; respectively, P = 0.24). The group walked > 350 meters distance was higher than the < 350 meters group after 2 months of operation (436 ± 78 meters vs. 348 ± 87 meters; P <0.01). The quality of life was lower in the < 350 meters group compared to the > 350 meters group in the preoperative period in the following domains: functional capabilities, limitations due to physical aspects, overall health feelings, vitality, and social aspects. Quality of life improved after two months in both groups. CONCLUSIONS: The six-minute walk test at the preoperative time is associated with the quality of life after two months of coronary artery bypass grafting. In overall, quality of life has improved in all patients. The improvement in the quality of life was greater in those patients who walked distances lower than 350 meters at the preoperative time.

Can neuroimaging be used as a support to diagnosis of borderline personality disorder? An approach based on computational neuroanatomy and machine learning.

Several recent studies in literature have identified brain morphological alterations associated to Borderline Personality Disorder (BPD) patients. These findings are reported by studies based on voxel-based-morphometry analysis of structural MRI data, comparing mean gray-matter concentration between groups of BPD patients and healthy controls. On the other hand, mean differences between groups are not informative about the discriminative value of neuroimaging data to predict the group of individual subjects. In this paper, we go beyond mean differences analyses, and explore to what extent individual BPD patients can be differentiated from controls (25 subjects in each group), using a combination of automated-morphometric tools for regional cortical thickness/volumetric estimation and Support Vector Machine classifier. The approach included a feature selection step in order to identify the regions containing most discriminative information. The accuracy of this classifier was evaluated using the leave-one-subject-out procedure. The brain regions indicated as containing relevant information to discriminate groups were the orbitofrontal, rostral anterior cingulate, posterior cingulate, middle temporal cortices, among others. These areas, which are distinctively involved in emotional and affect regulation of BPD patients, were the most informative regions to achieve both sensitivity and specificity values of 80% in SVM classification. The findings suggest that this new methodology can add clinical and potential diagnostic value to neuroimaging of psychiatric disorders.

The effect on hemolysis of the raceway profile of roller pumps used in cardiopulmonary bypass.

This study aims at the influence on hemolysis of the differences between the maximum and minimum amplitudes of pressure in the outlet of three roller pump models adjusted by dynamic calibration method. Tests were performed with silicone tubes (½ × (3)/(16) inches) in fluid analogous to blood and fresh bovine blood from slaughterhouse. Tests with analogous solution to blood were performed varying the dynamic calibration pressure between 78 and 500 mm Hg. Tests with fresh bovine blood were performed with the three pumps simultaneously, and pressure differences and free hemoglobin in the plasma were measured during 360 minutes. Tests with both analogous solution to blood and fresh bovine blood showed differences of mean pressures of pump 2 related to pumps 1 and 3 (p < 0.01). The different models of roller pumps analyzed presented differences in pressure amplitudes (p < 0.01) and hemolysis (p < 0.01) adjusted for the same dynamic calibration pressure. Raceway profile of pump 2 resulted in smaller pressure amplitude, implying lower hemolysis rate compared with pumps 1 and 3.

The influence of the residual stress in silicone tubes in the calibration methods of roller pumps used in cardiopulmonary bypass.

The rotation of rollers in cardiopulmonary bypass pumps propels the blood through various devices to reach the patient. Very occlusive settings may squeeze red blood cells, whereas a nonocclusive setting may result in retrograde flow. Occlusion of roller pumps may be regulated either by measuring the drop rate or by dynamic calibration. This study evaluated the influence of silicone tubing residual stress found on pump regulation. Silicone tubes obtained from two different suppliers were used in 6-inch DeBakey roller pumps. The variations occurring over time in the measurements of drop rate, dynamic calibration, and tube residual stress were analyzed. Covariance analysis of the four linear regressions has shown a progressive and accentuated reduction in drop rate (p < 0.002). It is noticeable that the angular coefficients of the drop rate measurements of the four silicone tubes are the same (p > 0.56). This reduction in drop rate measurements may affect the regulation of the pumps before surgical procedures. One probable cause for this reduction is the residual stress found in the silicone tubes. Settings based on the dynamic calibration process tended to be repeated over time. Simple linear regression test (angular coefficient equals zero) has shown a p > 0.79 showing no interference of the silicone tubes residual stress on dynamic calibration, suggesting that one should use this method to calibrate roller pumps.

Early changes in contractility indices and fibrosis in two minimally invasive congestive heart failure models.

BACKGROUND: Heart failure is a common and often fatal disease. Numerous animal models are used to study its aetiology, progression and treatment. This article aims to demonstrate two minimally invasive models of congestive heart failure in a rabbit model and a precise method to assess cardiac performance. METHODS: Fifty New Zealand White rabbits underwent cervicotomy incision and were then divided into three groups. Aortic regurgitation (AR group) was induced in 17 animals by catheter lesion through the right carotid artery, proximal aortic constriction (AC group) was created in 17 animals by metallic clip placement in the ascending aorta through a neck incision, while 16 animals served as controls (CO group). Eight weeks later, myocardial function and contractility indices were assessed by sonomicrometry crystals. Hearts were then collected for morphometric measurements and left ventricular tissues were subjected to immunohistochemical analysis of fibrosis, necrosis and apoptosis. Statistical analysis was by analysis of variance (ANOVA) with a Dunnett's post hoc test or by Kruskal-Wallis test with Dunn's post hoc test as appropriate, with significance at p< or =0.05. RESULTS: The model of aortic regurgitation indicated early stages of heart failure by volume overload with increased end-diastolic and end-systolic volumes, stroke volume, cardiac output and pressure-volume loop areas. The elastance was higher in the control group compared with that in the AC and AR groups (131.00+/-51.27 vs 88.77+/-40.11 vs 75.29+/-50.70; p=0.01). The preload recruitable stroke work was higher in the control group compared with that in the AC and AR groups (47.70+/-14.19 vs 33.87+/-7.46 vs 38.58+/-9.45; p=0.01). Aortic constriction produced left ventricular concentric hypertrophy. Fibrosis appeared in both heart failure models and was elevated by aortic constriction when compared with that in controls. Necrosis and apoptosis indices were very low in all the groups. Clinical signs of congestive heart failure were not present. CONCLUSIONS: The two heart failure models we describe were relatively simple to create and maintain, minimally invasive, accurate, inexpensive and, importantly, had a low mortality rate. These models rapidly induced deterioration of contractility indices and onset of fibrosis, the hallmarks of early myocardial dysfunction associated with heart failure. Sonomicrometry assessments were able to detect early contractility changes prior to clinical signs.

Use of (all-blood) miniplegia versus crystalloid cardioplegia in an experimental model of acute myocardial ischemia.

PURPOSE: Several methods of myocardial protection have been used. The use of all-blood solutions modified with glutamate and aspartate has increased. Its use in situations of acute ischemia provides improved contractile function, "resuscitating" the previously lesioned muscle. The dilution preconized by literature is around 25% of the hematocrit. The present study evaluates an all-blood cardioplegia solution with tepid 1% dilution, denominated miniplegia. MATERIAL AND METHOD: Pigs of the Large-White breed were used with an isolated heart and perfused with blood of a support animal. Three groups (n = 7 per group) were designated with the following treatments: Control group (CO), St. Thomas solution (ST), continuous normothermic all-blood solutions (SG). After the stabilization period, systolic pressure (PS), diastolic pressure (PD), developed pressure (PD), stress of the wall, elastance, and passive stiffness were recorded. The hearts were submitted to 30 minutes of regional ischemia with the clamping of the anterior interventricular artery, and subsequently to 90 minutes of global ischemia with the use of the three different treatments during this period. At the beginning of global ischemia, the coronary clamp was removed. The hearts were again reperfused. Upon three minutes into reperfusion the hearts were defibrillated when necessary. Measurements were taken every 30 minutes to 90 minutes into reperfusion. RESULTS: The SG presented a better recovery of the ventricular function in several of the parameters recorded. The ST group was inferior to the SG group, which in turn was superior to the CO group in some of the parameters analyzed. A higher number of defibrillations were needed to reestablish coordinated heart beats in the ST and CO groups. There were no differences related to the percentage of wet weight between the SG and ST groups, and the percentage was higher in the CO group. CONCLUSION: The use of all-blood miniplegia provided superior protection when compared to global ischemia or crystalloid cardioplegia in acutely ischemic hearts. The model employed is very close to the clinical situation due to the use of blood as a perfusate.

Endovascular treatment of pseudoaneurysm of the thoracic aorta from a firearm injury.

A 24-year-old male patient was the victim of a firearm wound that penetrated the thorax. He arrived at another hospital hemodynamically unstable and was submitted to exploratory surgery by means of bithoracotomy. A lesion of the left branch of the pulmonary artery was detected and successfully repaired. He was submitted for computer-aided tomography on the fifth postoperative day, and a lesion of the mid-thoracic aorta was detected, which formed a saccular image. Considering that the patient had already been submitted to a bithoracotomy and that a direct approach to repair would involve another thoracotomy within a short period of time, endovascular treatment was chosen in our hospital. The procedure was performed under fluoroscopy. A second computer-aided tomography indicated adequate treatment of the lesion, with no indication of an endoleak. He has undergone ambulatory follow-up for 36 months without any problem related to the procedure. While endovascular treatment of the aorta has developed enormously, multicenter studies are needed to better define the long-term results of this approach.