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Objective: To study neurodevelopmental outcome in a two year cohort of extremely low birthweight (ELBW) infants at 18 months corrected age, to compare the development of the ELBW infant subcohort [...]

Aim: Nitric oxide (NO) is an important mediator required for neonatal pulmonary circulatory adaptation and for pulmonary defence. Both deficient and excessive NO production have been proposed to play a role in neonatal lung disease. This study aimed to establish a method that allows direct measurement of exhaled and nasal NO concentrations in newborn infants who require intubation and ventilation.Methods: A rapid-response chemiluminescence NO analyser was used. Gas was sampled from the endotracheal intubation tube, and tidal volumes and flow rates were measured. The nasal NO was sampled from the non-intubated nostril. The accuracy of the method was validated using a lung model. NO levels from six preterm and six term/near-term newborns were studied. Measurements were performed on a daily basis during the first week.Results: An expiration >0.2 s in duration with a flow rate >1.7 ml s(-1) could be accurately analysed for the presence of >1 parts per billion of NO. The very preterm infants with neonatal lung disease had a different postnatal NO output pattern from the lower and upper airways compared with the ventilated term/near-term infants.Conclusion: A novel method for measurement of exhaled NO of an intubated newborn is presented. The possible association of exhaled NO concentration with the development of chronic lung disease remains to be studied. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether and which of the cerebral microdialysis parameters are predictive of postoperative outcome after an experimental 75-min period of hypothermic circulatory arrest (HCA) in a chronic porcine model.Design: Seventy-four juvenile female pigs underwent a 75-min period of HCA at 20 degrees C. A microdialysis catheter was placed into the cortex gray matter and brain extracellular concentrations of glucose, lactate, glycerol and glutamate were measured throughout the experiment by enzymatic methods using a microdialysis analyzer. Surviving animals were sacrificed on the 7th postoperative day and histopathological examination of the brain was performed.Results: Brain glucose concentrations were higher in animals that survived (p = 0.017), especially from the 90-min until the 7-h interval after the start of rewarming. The blood venous concentrations of glucose were also higher among survivors, and correlated significantly with the brain glucose levels at 2-h and 4-h intervals after the start of rewarming. Higher concentrations of brain lactate, glycerol and glutamate were observed throughout the study among animals that died postoperatively. Brain glutamate and glycerol concentrations were significantly, negatively correlated with brain glucose concentrations. The lactate/glucose ratio was significantly lower among survivors during the postoperative period (p=0.014). Furthermore, brain glucose concentrations were higher and brain glycerol concentrations lower among the animals that did not develop brain infarction, but such differences did not reach statistical significance.Conclusion: Cerebral microdialysis is a useful tool for cerebral monitoring during experimental HCA. Low brain glucose concentrations and high brain lactate/glucose ratios after HCA are strong predictors of postoperative death. Brain glucose concentrations are negatively correlated with brain glycerol and glutamate concentrations. [ABSTRACT FROM AUTHOR]

Objective: Serum S-100beta protein is suggested to be a neurobiochemical marker of brain injury after cardiac and aortic arch surgery. The aim of the present study was to investigate the predictive value of S-100beta protein with respect to histopathological analysis of the brain after a prolonged period of hypothermic circulatory arrest (HCA).Methods: Eighteen pigs (21 to 31 kg) underwent a 75 min period of HCA at 20 degrees C. Serum concentrations of S-100beta were assayed in mixed venous blood before and 2, 4, 7 and 20 h after HCA. A semiquantitative post-mortem histopathological analysis scoring all main regions of the brain was carried out in every animal.Results: All animals were stable during and after cardiopulmonary bypass (CPB) and survived at least to the first postoperative day. Ten of the 18 animals survived 7 days after surgery and were electively sacrificed. Animals with severe histopathological injury showed higher serum S-100beta protein levels at every time point after HCA. The strongest correlation between the total histopathologic score and serum S-100beta levels was found at 7 h after HCA (tau = 0.422 and p = 0.023).Conclusion: Serum S-100beta protein levels correlate with histopathological injury after a prolonged period of HCA in pigs. This finding supports the results of previous studies suggesting the potential accuracy of S-100beta in the prediction of brain injury after cardiac surgery. [ABSTRACT FROM AUTHOR]

Previous studies have shown that although retrograde cerebral perfusion (RCP) improves cerebral outcome during hypothermic circulatory arrest (HCA), RCP exposes the brain to subsequent edema. In this study, we have compared intermittent RCP (I-RCP) with continuous RCP (C-RCP) and HCA alone to determine whether the rate of fluid sequestration can be decreased without losing the beneficial effects of RCP. Eighteen pigs were randomly assigned to undergo 75 min of I-RCP, C-RCP or HCA at 20 degrees C. Hemodynamic and metabolic measurements were carried out for upto 20 h. Behavioral assessments were examined until day 7, when histopathologic analysis of the brain was performed. The median amount of fluid sequestered was 145 ml after C-RCP and -50 ml after I-RCP (p = 0.04). The mean brain weight of the animals that died within the first postoperative day was significantly higher than that in electively sacrificed animals in the C-RCP group (p = 0.04). These data suggest that if RCP is implemented intermittently, the rate of cerebral edema can be decreased, without compromising the benefits of this strategy. [ABSTRACT FROM AUTHOR]

Objectives: According to the manufacturer, the Hemochron ACT-LR cuvette is designated for heparin concentrations of 0 to 2.5 IU/mL, while the optimal concentration range for the ACT+ cartridge is 1 to 6 IU/mL. We hypothesized that at low to moderate heparin concentrations, the ACT-LR is more reliable than the ACT+., Design: An in vitro study., Setting: A tertiary care university hospital., Participants: Twenty healthy adult volunteers., Interventions: Donor blood samples were spiked with unfractionated heparin to concentrations of 0, 0.5, 1.0, 1.5, 2.0, and 2.5 IU/mL. From each concentration, 3 measurements were made with each test cassette using 3 different Hemochron Signature Elite devices, for a total of 720 ACT tests. The Bland-Altman method and intraclass correlation coefficients were used to analyze the data., Measurements and Main Results: All 360 ACT+ tests yielded a result. Of 360, 38 (11%) ACT-LR tests ran above the upper measurement range; of these, 36 were from the 120 measurements at heparin concentrations ≥2.0 IU/mL. The bias between all ACT-LR and ACT+ measurements ​​was 52 (95% CI, 48-56) celite seconds, and the limits of agreement were wide. Based on the intraclass correlation coefficients, the reliability of ACT+ was better than or equal to that of ACT-LR., Conclusions: The performance of ACT+ is equal to that of ACT-LR up to a concentration of 0.5 IU/mL, above which ACT+ is superior to ACT-LR, questioning the rationale for a specific low-range test. However, there is a significant bias between ACT-LR and ACT+ measurements that needs to be considered if switching from one test to the other., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: This trial analyzed the effect of sub-ulcer foam sclerotherapy in patients with venous leg ulcer (VLU)., Design: Randomized controlled trial., Methods: This trial recruited patients with VLUs to receive either sub-ulcer foam sclerotherapy and compression therapy (study group) or compression therapy only (control group). The primary outcome of this study was the change in the venous ulcer area at 4 weeks. The feasibility, safety, and complications of the sub-ulcer foam sclerotherapy were recorded., Results: Of 23 patients included, 12 were randomized to study group and 11 to control group. Preoperatively, the average ulcer areas were 5.8 cm 2 in both groups. At 4 weeks, the average reductions in ulcer areas were 4.0 cm 2 (SD 3.1) in the study group (95% CI 2.0 to 5.9, p = .001) and 2.0 cm 2 (SD 3.1) in the control group (95% CI: -0.1 to 4.1, p = .051). No differences in complications were recorded., Conclusions: At 1-month sub-ulcer foam sclerotherapy and compression therapy reduced the ulcer area statistically significantly, whereas compression therapy alone did not. Sub-ulcer foam sclerotherapy could be a good addition to superficial venous insufficiency treatment in patients with VLU.ClinicalTrials.gov identifier NCT03795064., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: For this retrospective study, we analyzed the sub-ulcer foam sclerotherapy technique in patients with venous leg ulcer (VLU)., Methods: This study included 134 patients treated with sub-ulcer foam sclerotherapy at the Oulu University Hospital vascular outpatient clinic from January 2012 to December 2021. All included patients received sub-ulcer foam sclerotherapy as part of the treatment strategy for superficial venous insufficiency. Compression therapy and local wound care were organized for VLU treatment. A follow-up visit was scheduled for one month after the sub-ulcer foam sclerotherapy. Change in ulcer size, local (skin necrosis, infection) or systemic (deep vein thrombosis, pulmonary embolism) complications, and time to ulcer healing were monitored. The occurrence of major limb-related complications (amputation, surgical revision) was monitored for one year postoperatively., Results: One month after sub-ulcer treatment, ulcers were smaller or completely healed in 108 (81%) patients. Ulcer healing was completed in 123 (92%) patients at one year and 131 (98%) patients at two years. Complications were recorded in four (3%) patients, three (2%) who were diagnosed with erysipelas requiring antibiotic treatment and one (1%) patient diagnosed with local dermatitis. During the one-year follow-up, no major limb-related complications (surgical revisions or amputations) arose., Conclusions: Sub-ulcer foam sclerotherapy may be a feasible addition to superficial vein reflux elimination in patients with VLU and a low risk for complications., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Opinions on the treatment of varicose tributaries in relation to saphenous ablation in varicose disease vary. Moreover, the possible role of the tributaries regarding the recurrence of varicose disease remains unclear. The aim of the FinnTrunk study is to compare two different treatment strategies for varicose disease in a randomized setting. In group one, the initial treatment will entail endovenous laser ablation (EVLA) of the incompetent saphenous trunk without tributary treatment. In group two, the varicose tributaries will be treated with ultrasound-guided foam sclerotherapy (UGFS) concomitantly with truncal ablation. The primary outcome measure is the need for additional procedures during the follow-up. The secondary outcome measures are the cost of treatment and recurrence of varicose disease., Methods: Consecutive patients with symptomatic varicose disease (CEAP clinical class C2-C3) will be screened for the study. Patients who fulfil the study criteria and give their informed consent will be scheduled for the procedure and randomized to either study group. Patients will be followed-up at 3 months, 1 year, 3 years, and 5 years. The post-procedure pain score based on a numeric rating scale (NRS) and also the use of analgesics, as well as possible procedure-related complications will be recorded at 3 months. Patient-reported outcome measures (PROMs) will be recorded at 1 year. Data pertaining to the additional treatment of varicose tributaries, the Aberdeen Varicose Vein Questionnaire (AVVQ), the Venous Clinical Severity Score (VCSS), and the health-related quality of life (EQ-5D-5L) will be collected at each follow-up visit. A duplex ultrasound (DUS) examination will be performed at each visit, and data on varicose tributaries and the need for additional treatment will be recorded., Trial Registration: Registered on ClinicalTrials.gov, ID NCT04774939., Competing Interests: he authors have declared that no competing interests exist., (Copyright: © 2023 Viljamaa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This retrospective trial analyzed the effect of predetermined variables on venous ulcer healing after endovenous ablation of insufficient veins., Methods: A total of 259 patients presenting 273 venous leg ulcers (VLUs) at Oulu University Hospital vascular outpatient clinic between January 2010 and December 2020 were included in the study. In addition to compression therapy, all patients received endovenous ablation (endothermal ablation and/or foam sclerotherapy) to promote venous healing. The hazard ratio (HR) for an ulcer to heal was analyzed in univariate analysis of predetermined factors, including age, sex, recurrent venous ulcer, presence of great saphenous vein or small saphenous vein reflux, persistent superficial vein reflux after ablation, recanalization in treated segments, ulcer age, body mass index >35 kg/m 2 , history of deep vein thrombosis, history of erysipelas, ability to move, smoking, hypertension, atrial fibrillation, coronary artery disease, diabetes mellitus, and cardiac insufficiency. Logistic regression was used in a multivariate analysis to identify independent risk factors for ulcer healing., Results: In the univariate analysis, healing was negatively associated with persistent superficial vein reflux after ablation (HR, 0.117; 95% confidence interval [CI], 0.088-0.354), recanalization in treated segments (HR, 0.161; 95% CI, 0.060-0.433), nonambulatory patient (HR, 0.322; 95% CI, 0.130-0.800), history of deep vein thrombosis (HR, 0.518; 95% CI, 0.294-0.910), and presence of small saphenous vein reflux (HR, 0.565; 95% CI, 0.384-0.830). Independent risk factors included persistent superficial vein reflux after ablation (HR, 0.123; 95% CI, 0.0051-0.295). All the patients in the persistent superficial vein reflux group had their VLUs eventually healed after further endovenous treatment., Conclusions: When treating patients with VLUs, persistent superficial vein reflux after ablation was negatively associated with ulcer healing. After additional endovenous ablative treatment, ulcers with persistent reflux eventually healed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The benefits of postoperative compression are not well established following radiofrequency ablation of the truncal vein and concomitant foam sclerotherapy., Methods: A total of 104 patients were randomized: Postoperatively, 54 patients received no compression and 50 patients received class II thigh-high compression. The primary outcome for this study was the difference between means on postoperative pain scores over the first 10 days follow-up measured on a visual analog scale (VAS) from 0 to 100 mm (prespecified delta 10 mm)., Results: The difference between means in no compression and compression group on postoperative pain scores over the 10 days follow-up was 2.1 mm (95% confidence interval -5.1-9.3 mm; p = 0.28) indicating non-inferiority. Patients in the no compression group were more satisfied with the visual appearance of the treated leg at 1 month ( p = 0.003)., Conclusion: Over the first 10 postoperative days, no compression was non-inferior to compression on pain scores.

Background: The purpose of this study was with a simple clinical setting to compare skin temperature changes in the feet before and after revascularization and to identify possible correlation between ankle brachial index (ABI) and toe pressure (TP) values and foot skin temperature patient with and without diabetes., Methods: Forty outpatient clinic patients were measured ABI, TP, and the skin temperature using infrared thermography (IRT) at the foot before and after revascularization. Patients in the revascularization group were divided into subgroups depending on whether they had diabetes or not and a wound or not., Results: There were clear correlation between increase of ABI and TP and increase of the mean skin temperature on the feet after revascularization. The temperature was higher and the temperature change was greater among patients with diabetes. Side-to-side temperature difference between the revascularized feet and contralateral feet decreased after treatment. The mean temperature was higher in the feet with wound whether patient had diabetes mellitus or not., Conclusion: The simple, prompt, and noninvasive IRT procedure showed its potential as a follow-up tool among patients with diabetes or peripheral arterial disease and previous lower limb revascularization.

Objective: We evaluated the effect of first-visit foam sclerotherapy compared with scheduled treatment for patients with venous ulceration., Methods: The study design was a retrospective comparative study. From December 2009 to October 2019, a total of 245 venous ulcers in 214 patients (including recurrent ulcers) were treated at Oulu University Hospital. Of these 245 venous ulcers, 143 were treated with first-visit foam sclerotherapy (group A) and 102 with scheduled treatment (group B). All patients received endovenous ablation (foam sclerotherapy and/or endothermal ablation) and compression therapy to promote venous ulcer healing. The primary outcome was the interval to ulcer healing, determined by Kaplan-Meier survival analysis. The secondary outcomes included the time to ulcer healing from the receipt of referral and ulcer recurrence., Results: The median time to ulcer healing was 2.3 months for group A and 3.2 months for group B (P = .002). The estimated median ulcer healing times after referral for a first session of endovenous ablation were 2.7 months with a delay of <1 month from the referral, 3.3 months with a delay of 1 to 2 months, and 5.0 months with a delay of >2 months (P = .002). In group A, recurrent ulcers were recorded for 11 patients (7.7%). In group B, recurrent ulcers were recorded for 12 patients (11.8%; P = .281)., Conclusions: The results of the present retrospective comparative study support first-visit foam sclerotherapy as an effective method to initiate endovenous ablation to promote venous ulcer healing. In venous ulcers, delays to endovenous ablation should be avoided whenever possible., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To compare post-operative compression with no compression, after radiofrequency endothermal ablation (RFA) of a truncal varicose vein and concomitant foam sclerotherapy of the tributaries., Methods: This prospective randomised controlled, non-inferiority trial recruited patients from two centres in Northern Ostrobothnia, Finland. Patients with clinical class C2-C4 chronic venous disease were randomised to receive no compression after the operation, or to receive compression stockings continuously for two days, and then, during the daytime for five days. In follow up visits, additional foam sclerotherapy was performed for symptoms of distal incompetence. Patients were followed up for six months. The primary outcome was occlusion of the RFA treated truncal vein at six months. Secondary outcomes were return to full activity within 14 days, Aberdeen Varicose Vein Questionnaire (AVVQ) score, post-operative pain, need for painkillers, and postprocedural complications., Results: Of 177 included patients, 90 were allocated to post-operative compression and 87 to no compression. At six months, both groups showed 100% occlusion rates in RFA treated truncal veins (95% confidence interval -0.043-0.042). Within 14 days of treatment, full physical activity was achieved by 87% of the compression group and 81% of the no compression group, (p = .29). At six months, the AVVQ scores were comparable and significantly improved in both groups, compared with baseline. Pain scores were comparable between groups, in day to day analyses, and they were significantly lower in both groups on day 10, compared with pre-operative pain caused by varicose veins. On average, post-operative pain medication was used for 2.3 days and for 2.8 days in the compression and no compression groups, respectively (p = .28). Complications throughout the six month follow up were comparable between groups, although skin rash/blisters occurred more often in the compression group (p = .01)., Conclusion: After treating C2-C4 varicose veins with RFA and concomitant foam sclerotherapy, no post-operative compression was non-inferior to post-operative compression, in terms of safety and efficacy. ClinicalTrials.gov Identifier: NCT02890563., (Copyright © 2019 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objectives: Previous studies have suggested that gastrointestinal integrity is compromised after cardiopulmonary bypass (CPB). We compared the effects of prolonged minimized (MCPB) and conventional CPB (CCPB) on intestinal mucosal integrity by determining mucosal damage, epithelial cell proliferation rate and distribution of tight junction proteins in a porcine model., Design: Fourteen animals were randomly assigned to undergo 240 minutes of mild hypothermic MCPB or CCPB. Ileal and colonic biopsies were obtained prior and at the end of CPB. Mucosal damage was determined under light microscopic evaluation. Immunohistochemistry was used to investigate epithelial expression of Ki-67 as a measure of cell proliferation rate and claudin-1, 2, 3, 4, 5, and 7 as elements of tight junctions., Results: In colonic biopsies, independent of the circuit type used, moderate mucosal damage was observed as indicated by focal epithelial damage, increased epithelial cell proliferation and decreased expression of tight junction protein claudin-4., Conclusions: Colonic mucosal damage was observed similarly in MCPB and CCPB. Based on these results, the effects of MCPB on intestinal mucosal stability are similar to those of CCPB.

Aim: We have evaluated the outcome after coronary artery bypass surgery in very high risk patients (additive EuroSCORE ≥ 10). The impact of beating heart coronary artery bypass surgery (BHCAB) on their outcome has been evaluated., Methods: Retrospective study including 160 consecutive patients with additive EuroSCORE ≥ 10., Results: . The overall survival rates at 30-day, 1-year, 3-year and 5-year were 83.8%, 76.0%, 72.4% and 66.8%, respectively. Baseline cardiac index (O.R. 0.20, 95%C.I. 0.08-0.53), preoperative inotropic support (O.R. 4.55, 95%C.I. 1.41-14.73) and preoperative resuscitation (O.R. 3.937, 95%C.I. 1.02-15.26) were independent predictors of 30-day mortality. Baseline cardiac index (R.R. 0.48, 95%C.I. 0.28-0.85), left ventricular ejection fraction (P=0.032), preoperative use of intraaortic balloon pump (R.R. 3.22, 95% C.I. 1.50-6.93), preoperative tracheal intubation (R.R. 3.44, 95%C.I. 1.37-8.68) and creatinine (R.R. 1.004, 95%C.I. 1.00-1.01) were independent predictors of late death. OPCAB/BHCAB was associated with somewhat lower 30-day mortality rate (16.2% vs. 18.0%, P=0.73), stroke (2.0% vs. 4.9%, P=0.37), red blood cells transfusion (3.4 vs. 5.4 units, P=0.004) and combined adverse outcome (43.4% vs. 50.8%, P=0.42). OPCAB/BHCAB surgeons compared with surgeons with a prevalent conventional approach achieved slightly better the 30-day mortality rate (16.7% vs. 27.9%, P=0.15) and stroke rate (2.8% vs. 4.7%, P=0.60) and 5-year survival rate (65.3% vs. 57.4%, P=0.35)., Conclusion: Despite their poor immediate postoperative outcome, 5-year survival of these high risk patients is satisfactory and supports efforts in the treatment of this very high risk population. A more confident approach toward OPCAB/BHCAB is also suggested in these patients.

Background: We have evaluated the immediate and intermediate outcome after off-pump (OPCAB) and conventional on-pump coronary artery bypass surgery (CCAB) in patients with unstable angina pectoris requiring nitrates infusion until arrival in the operating room., Methods: A consecutive series of 153 and 161 patients with unrelenting angina pectoris underwent CCAB and OPCAB, respectively. Conversion from OPCAB to beating heart surgery with perfusion occurred in 4 patients., Results: The OPCAB patients had a significantly higher operative risk than CCAB patients (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 13.8 +/- 12.8% vs 10.5 +/- 10.0%, p = 0.005). In the overall series, a lower 30-day postoperative mortality was observed among OPCAB patients (1.9% vs 3.9%, p = 0.33), the difference increased along the logistic EuroSCORE tertiles (upper tertile: 3.2% vs 9.5%, p = 0.14), but failed to reach statistical significance. Similar results have been observed among one-to-one propensity score matched pairs. The results of three surgeons who treated most of their patients (96.9%) with OPCAB were compared with those of three surgeons who used, in most of cases (97.1%), the CCAB technique. When adjusted for logistic EuroSCORE, patients operated on by CCAB surgeons had a significantly higher 30-day postoperative mortality (7.1% vs 2.1%, p = 0.04; odds ratio [OR] 10.143; 95% confidence interval [CI] 1.084 to 94.945) as well as a higher risk of combined adverse events (47.1% vs. 35.1%, p = 0.009; OR 2.586; 95% CI 1.274 to 5.250)., Conclusions: This study provided further evidence on the safety and efficacy of OPCAB in the treatment of high-risk patients. A dedicated approach to OPCAB seems to provide particularly good results. Such findings further support a more confident approach with OPCAB in these patients.

Background: The superiority of the pH-stat to the alpha-stat acid-base strategy during cardiopulmonary bypass as a neuroprotective method during hypothermic circulatory arrest is still controversial. In the present study, brain metabolism and outcome have been evaluated in a surviving model of experimental hypothermic circulatory arrest., Methods: Twenty pigs undergoing 75-minutes of hypothermic circulatory arrest at a brain temperature of 18 degrees C were randomly assigned to the alpha-stat (n = 10) or pH-stat (n = 10) strategy during cardiopulmonary bypass., Results: The 7-day survival rate was 90% (9 of 10) in the pH-stat group and 10% (1 of 10) in the alpha-stat group. At the end of cooling, pH-stat strategy was associated with significantly lower brain lactate and pyruvate concentrations and brain lactate-glucose ratio. After reperfusion, brain concentrations of glycerol, lactate, pyruvate, and lactate-glucose ratio were significantly lower in the pH-stat group. This strategy was associated with a faster rise of brain tissue temperature and reoxygenation on reperfusion, which is likely secondary to improved cerebral perfusion., Conclusions: During cardiopulmonary bypass before and after a period of hypothermic circulatory arrest, acid-base management according to the pH-stat principles seemed to be associated with less derangements in cerebral metabolism, lower intracranial pressures, and excellent behavioral recovery and survival outcome. Because there is strong evidence of the beneficial metabolic effects related to this method, further studies using an experimental model of combined HCA and embolic brain injury are required to exclude a possible increased risk of cerebral embolism associated with the pH-stat strategy.

Objective: To evaluate whether electroencephalography (EEG) recovery could be considered a reliable marker of brain injury after experimental hypothermic circulatory arrest (HCA)., Design: Cortical electrical activity was registered before and after a 75-min period of HCA in 27 pigs that survived 7 days after the experiment. The sum of EEG bursts was counted as a percentage of the sum of artifact-free bursts and suppressions, and this percentage was used as a measure of EEG activity in the analysis., Results: Brain infarction developed in 13 animals (48.1%), in 12 cases (44.4%) having involved the cortex, in 1 case the thalamus (3.7%) and in another the hippocampus (3.7%). The mean EEG burst percentage significantly correlated with the total brain histopathological score (rho = -0.588, P = 0.001). EEG burst percentage from the 2 h 20 min to the 7 h 20 min interval correlated with the total brain histopathological score and with the cortex, brainstem and cerebellum scores. The mean EEG burst percentage rate was higher, but not significantly, among the animals without brain infarction (38.5% vs 32.4%), but such a difference was significant at the 3 h 20 min postoperative interval (P = 0.02). The mean EEG burst percentage significantly correlated with brain glucose concentration at the 1 h interval (rho = 0.387; P = 0.046), brain lactate concentration at the 2 h interval (rho = -0.431; P = 0.025), and the brain lactate/glucose ratio at the 1 h 30 min interval from the start of rewarming (rho = -0.433; P = 0.024)., Conclusion: A decreased EEG burst percentage seems to be associated with an increased risk of developing histologically evident brain ischemic injury in the cortex, brainstem and cerebellum after experimental HCA.

Background: The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest., Methods: Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37 degrees C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37 degrees C., Results: The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group., Conclusions: Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.

Objective: Fructose-1,6-bisphosphate is a high-energy intermediate in the anaerobic metabolism. It enhances glycolysis, preserves cellular adenosine triphosphate, and prevents the increase of intracellular calcium during ischemia. The potential neuroprotective effect of fructose-1,6-bisphosphate during hypothermic circulatory arrest was evaluated in a surviving porcine model., Methods: Twenty-four pigs were randomly assigned to receive two intravenous infusions of either fructose-1,6-bisphosphate (500 mg/kg) or saline solution. The first infusion was given immediately before a 75-minute period of hypothermic circulatory arrest and the second was given immediately after hypothermic circulatory arrest., Results: The 7-day survivals were 83.3% in the fructose-1,6-bisphosphate group and 41.7% in the control group (P =.09). The treated animals had significantly better postoperative behavioral scores. The administration of fructose-1,6-bisphosphate was associated with higher venous phosphate and sodium levels, lower venous ionized calcium levels, higher blood osmolarity, and a better fluid balance. Intracranial pressure and venous creatine kinase isoenzyme MB were significantly lower in the fructose-1,6-bisphosphate group during rewarming (P =.01 and P =.001, respectively). Among the treated animals, brain glucose, pyruvate and lactate levels tended to be higher, brain glycerol levels tended to be lower, and the histopathologic score of the brain was significantly lower (P =.04)., Conclusions: Intravenous administration of fructose-1,6-bisphosphate at 500 mg/kg before and after hypothermic circulatory arrest in a surviving porcine model was associated with better survival, behavioral outcome, and histopathologic score. The observed lower blood creatine kinase isoenzyme MB and brain glycerol levels and the higher brain glucose, pyruvate, and lactate levels in the fructose-1,6-bisphosphate group suggest that this drug has supportive effects on myocardial and brain metabolisms.

Objective: Recent studies have shown that erythropoietin protects neurons from glutamate toxicity and ischemia. This study was performed to evaluate the potential neuroprotective effect of erythropoietin during experimental hypothermic circulatory arrest., Methods: Twenty pigs were randomized to receive intravenously either 500 IU/kg recombinant human erythropoietin or saline before a 75-minute period of hypothermic circulatory arrest at an intracerebral temperature of 18 degrees C., Results: After the administration of erythropoietin, its concentration in the cerebrospinal fluid increased 4.5-fold 8 hours after the start of rewarming, whereas it did not increase in control animals. The 7-day survival rate was 60% in the erythropoietin group and 70% in the control group (P = 1.0). No significant differences were observed between the study groups in terms of electroencephalography, behavioral score, and histopathologic score. The erythropoietin group had higher vascular resistance and mean arterial pressure values, lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index., Conclusions: Administration of 500 IU/kg erythropoietin intravenously before hypothermic circulatory arrest was followed by an increased erythropoietin concentration in the cerebrospinal fluid. Although previous studies have demonstrated neuroprotective effects of erythropoietin during brain ischemia, the present study, using a chronic porcine model, failed to show any significant benefit after administration of erythropoietin in terms of mortality or brain histopathology. Lower intracerebral concentrations of glutamate and glycerol, higher brain tissue oxygen tension, and lower apoptotic index observed in the erythropoietin group, however, suggest that a distinct neuroprotective effect of erythropoietin might be achieved at different dosages and timing of administration.

Objective: An increase in intracranial pressure has been shown to threaten the outcome of patients with ischemic or traumatic brain injury. Its impact on the outcome of pigs undergoing hypothermic circulatory arrest has been evaluated in this study., Design: Fifty-six pigs underwent a 75-min period of hypothermic circulatory arrest at 20 degrees C. Intracranial pressure, cerebral microdialysis, hemodynamic and metabolic parameters were monitored throughout the experiment. The animals were allowed to survive until the 7th postoperative day and, then, electively killed., Results: The 7-day survival rate was 60.7%, and among survivors, 20 of them (58.8%) developed brain infarction. A significant increase in intracranial pressure as compared with the baseline level was observed since the end of cooling (p = 0.047) and the difference became larger during all the postoperative intervals (p < 0.0001). Animals that died postoperatively tended to have higher intracranial pressure levels during all the postoperative intervals, but such a difference reached significance only at the 4-h postoperative interval (p = 0.040). The same tendency was observed among animals that survived until the 7th postoperative day and that developed brain infarction or not, but the difference between these two groups did not reach statistical significance. The animals that died or developed postoperatively brain infarction had higher intracranial pressure values postoperatively as compared with those that survived without developing brain infarction and such a difference reached significance at the 2-h (p = 0.015) and 4-h postoperative intervals (p = 0.035). The peak intracranial pressure was 17.2 mmHg (IQR, 13.7-20.8) in animals that died or developed brain infarction and 14.1 mmHg (IQR, 11.8-16.4) in those that survived 7 days without developing brain infarction (p = NS)., Conclusion: Intracranial pressure increases significantly after 75 min of experimental hypothermic circulatory arrest and such an increase is associated with a high risk of postoperative death and brain infarction.

Objectives: We sought to evaluate the potential efficacy of prolonged mild hypothermia after hypothermic circulatory arrest., Methods: Twenty pigs, after a 75-minute period of hypothermic circulatory arrest, were randomly assigned to be rewarmed to 37 degrees C (normothermia group) or to 32 degrees C and kept at that temperature for 14 hours from the start of rewarming (hypothermia group)., Results: The 7-day survival was 30% in the hypothermia group and 70% in the normothermia group (P =.08). The hypothermia group had poorer postoperative behavioral scores than the normothermia group. Prolonged hypothermia was associated with lower oxygen extraction and consumption rates and higher mixed venous oxygen saturation levels during the first hours after hypothermic circulatory arrest. Decreased cardiac index, lower pH, and higher partial pressure of carbon dioxide were observed in the hypothermia group. There was a trend for beneficial effect of prolonged hypothermia in terms of lower brain lactate levels until the 4-hour interval and of intracranial pressure until the 10-hour interval. Postoperatively, total leukocyte and neutrophil counts were lower, and creatine kinase BB was significantly increased in the hypothermia group. At extubation, the hypothermia group had higher oxygen extraction rates and lower brain tissue oxygen tension., Conclusions: A 14-hour period of mild hypothermia after 75-minute hypothermic circulatory arrest seems to be associated with poor outcome. However, the results of this study suggest that mild hypothermia may preserve its efficacy when it is used for no longer than 4 hours, but the potentials of a shorter period of postoperative mild hypothermia still require further investigation.

Background: Lamotrigine and leukocyte filtration seem to improve cerebral protection during experimental hypothermic circulatory arrest (HCA). This study was performed to evaluate whether their combined use may further improve cerebral protection., Methods: Twenty-four pigs undergoing 75-minute period of HCA at 20 degrees C were randomly assigned to receive saline; lamotrigine (20 mg/kg) before HCA (L); or lamotrigine (20 mg/kg) before HCA plus leukocyte filtration before and after HCA (L + LF)., Results: Seven animals (87%) in the L + LF group, 4 (50%) in the L group, and 3 (37%) in the control group were alive on the seventh postoperative day. The median electroencephalogram burst recovery was 94% in the L + LF group (p = 0.024 versus control group), 81% in the L group, and 64% in the control group. Among the surviving animals, the median behavioral scores were 9, 9, and 6 at the seventh day, respectively (p = 0.005 between the L + LF group and the control group). The median histopathologic score was 14 in the L + LF group (p = 0.046 versus control group), 14.5 in the L group (p = 0.062 versus control group), and 21 in the control group., Conclusions: Lamotrigine has neuroprotective effect during HCA. The combined use of lamotrigine and LF may further improve the survival outcome.

Background: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present study was to determine the potential efficacy of memantine, an N -methyl-D -aspartate receptor antagonist, to mitigate cerebral injury after hypothermic circulatory arrest., Methods: Twenty pigs (23-33 kg) were randomly assigned to receive memantine (5 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. The intracerebral concentrations of glucose, lactate, glutamate, and glycerol were measured by means of enzymatic methods on a microdialysis analyzer. Daily behavioral assessment was performed until the animals died or were put to death on day 7. Histologic analysis of the brain was carried out in all animals., Results: In the memantine group, 5 of 10 animals survived 7 days compared with 9 of 10 in the placebo group. The median behavioral score at day 7 was 3.5 in the memantine group and 7.5 in the placebo group (P >.2). Among the surviving animals, medians were 9.0 and 8.0 on day 7 (P >.2), respectively. The medians of recovered electroencephalographic bursts were equal in both groups. The median of total histopathologic score was 16 in the memantine group and 14 in the placebo group (P >.2). There was a negative correlation between glutamate levels and electroencephalographic burst recovery (tau = -0.377, P =.043). A positive correlation was found between the highest individual glutamate value and histopathologic score (tau = 0.336, P =.045)., Conclusions: The present study demonstrates that memantine has no neuroprotective effect after hypothermic circulatory arrest in the pig. In addition, we have shown the accuracy of cerebral glutamate measurements to predict histopathologic injury after hypothermic ischemia.

Objectives: The aims of this prospective nationwide investigation were to establish the birth rate, mortality, and morbidity of extremely low birth weight (ELBW) infants in Finland in 1996-1997, and to analyze risk factors associated with poor outcome., Participants and Methods: The study population included all stillborn and live-born ELBW infants (birth weight: <1000 g; gestational age: at least 22 gestational weeks [GWs]), born in Finland between January 1, 1996 and December 31, 1997. Surviving infants were followed until discharge or to the age corresponding with 40 GWs. National ELBW infant register data with 101 prenatal and postnatal variables were used to calculate the mortality and morbidity rates. A total of 32 variables were included in risk factor analysis. The risk factors for death and intraventricular hemorrhage (IVH) of the live-born infants as well as for retinopathy of prematurity (ROP) and oxygen dependency of the surviving infants were analyzed using logistic regression models., Results: A total of 529 ELBW infants (.4% of all newborn infants) were born during the 2-year study. The perinatal mortality of ELBW infants was 55% and accounted for 39% of all perinatal deaths. Of all ELBW infants, 34% were stillborn, 21% died on days 0 through 6, and 3% on days 7 though 28. Neonatal mortality was 38% and postneonatal mortality was 2%. Of the infants who were alive at the age of 4 days, 88% survived. In infants surviving >12 hours, the overall incidence of respiratory distress syndrome (RDS) was 76%; of blood culture-positive septicemia, 22%; of IVH grades II through IV, 20%; and of necrotizing enterocolitis (NEC) with bowel perforation, 9%. The rate of IVH grades II through IV and NEC with bowel perforation decreased with increasing gestational age, but the incidence of RDS did not differ significantly between GWs 24 to 29. A total of 5 infants (2%) needed a shunt operation because of posthemorrhagic ventricular dilatation. Two hundred eleven ELBW infants (40% of all and 60% of live-born infants) survived until discharge or to the age corresponding with 40 GWs. The oxygen dependency rate at the age corresponding to 36 GWs was 39%, and 9% had ROP stage III-V. Neurological status was considered completely normal in 74% of the surviving infants. The proportions of infants born at 22 to 23, 24 to 25, 26 to 27, and 28 to 29 GWs with at least one disability (ROP, oxygen dependency, or abnormal neurological status) at the age corresponding to 36 GWs were 100%, 62%, 51%, and 45%, respectively. Birth weight <600 g and gestational age <25 GWs were the independent risks for death and short-term disability. The primary risk factor for IVH grades II through IV was RDS. Low 5-minute Apgar scores predicted poor prognosis, ie, death or IVH, and antenatal steroid treatment to mothers with threatening premature labor seemed to protect infants against these. Some differences were found in the mortality rates between the 5 university hospital districts: neonatal mortality was significantly lower (25% vs 44%) in one university hospital area and notably higher (53% vs 34%) in another area. Furthermore, significant differences were also found in morbidity, ie, oxygen dependency and ROP rates. Differences in perinatal (79% vs 45%) and neonatal (59% vs 32%) mortality rates were found between secondary and tertiary level hospitals., Conclusion: Our study shows that even with modern perinatal technology and care, intrauterine and early deaths of ELBW infants are common. The outcome of infants born at 22 to 23 GWs was unfavorable, but the prognosis improved rapidly with increasing maturity. The clear regional and hospital level differences detected in survival rates and in short-term outcome of ELBW infants emphasizes that the mortality and morbidity rates should be continuously followed and that differences should be evaluated in perinatal audit procedures. (ABSTRACT TRUNCATED)

Background: Ischemic cerebral injury follows a well-attested sequence of events, including 3 phases: depolarization, biochemical cascade, and reperfusion injury. Leukocyte infiltration and cytokine-mediated inflammatory reaction are known to play a pivotal role in the reperfusion phase. These events exacerbate the brain injury by impairing the normal microvascular perfusion and through the release of cytotoxic enzymes. The aim of the present study was to determine whether a leukocyte-depleting filter (LeukoGuard LG6, Pall Biomedical, Portsmouth, United Kingdom) could improve the cerebral outcome after hypothermic circulatory arrest., Methods: Twenty pigs (23-30 kg) were randomly assigned to undergo cardiopulmonary bypass with or without a leukocyte-depleting filter before and after a 75-minute period of hypothermic circulatory arrest at 20 degrees C. Electroencephalographic recovery, S-100beta protein levels, and cytokine levels (interleukin 1beta, interleukin 8, and tumor necrosis factor alpha) were recorded up to the first postoperative day. Postoperatively, all animals were evaluated daily until death or until electively being put to death on day 7 by using a quantitative behavioral score. A postmortem histologic analysis of the brain was carried out on all animals., Results: The rate of mortality was 2 of 10 in the leukocyte-depletion group and 5 of 10 in control animals. The risk for early death in control animals was 2.5 (95% confidence interval, 0.63-10.0) times higher than that of the leukocyte-depleted animals. The median behavioral score at day 7 was higher in the leukocyte-depletion group (8.5 vs 3.5; P =.04). The median of total histopathologic score was 8.5 in the leukocyte-depletion group and 15.5 in the control group (P =.005)., Conclusion: A leukocyte-depleting filter improves brain protection after a prolonged period of hypothermic circulatory arrest.

Background: Glutamate excitotoxicity has an important role in the development of brain injury after prolonged hypothermic circulatory arrest. The goal of the present studies was to determine the potential efficacy of lamotrigine, an Na(+) channel blocker, to mitigate cerebral injury after hypothermic circulatory arrest., Methods: Sixteen pigs (21-27 kg) were randomly assigned to receive lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period of hypothermic circulatory arrest (20 degrees C). Hemodynamic, electroencephalographic, and metabolic monitoring were carried out. S-100beta protein was determined up to the first postoperative morning. Daily behavioral assessment was performed until the animal died or was put to death on day 7. Histologic analysis of the brain was carried out in all animals., Results: Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among the animals that survived for 7 days, the median behavioral score was higher in the lamotrigine group (8 vs 7, P =.02). The medians of recovered electroencephalographic bursts in the lamotrigine group were higher than those in the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S-100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in the placebo group (P =.06)., Conclusions: The present data suggest that lamotrigine improves neurologic outcome after a prolonged period of hypothermic circulatory arrest.

Background: Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcome after prolonged hypothermic circulatory arrest. Here we have compared two temperatures of retrograde cerebral perfusion (15 degrees C and 25 degrees C) with hypothermic circulatory arrest at systemic hypothermia of 25 degrees C to clarify whether the possible benefit of retrograde cerebral perfusion may only be due to improved cooling effect., Methods: Eighteen pigs (23-27 kg) were randomly assigned to undergo 15 degrees C retrograde cerebral perfusion at systemic hypothermia of 25 degrees C, 25 degrees C retrograde cerebral perfusion at 25 degrees C systemic hypothermia, or hypothermic circulatory arrest at 25 degrees C for 40 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg during retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were performed until 4 hours after the start of rewarming. Daily behavioral assessment was done until death or until the animals were killed on day 7. Histopathologic analysis of the brain was carried out on all animals., Results: Epidural temperatures were lower in the 15 degrees C retrograde cerebral perfusion group during the intervention (P <.05). In the 15 degrees C retrograde cerebral perfusion group, 4 (67%) of 6 animals survived for 7 days compared with 3 (50%) of 6 in both the 25 degrees C retrograde cerebral perfusion and hypothermic circulatory arrest groups. The median total histopathologic score was 5 in the 15 degrees C retrograde cerebral perfusion group and 7 in the 25 degrees C retrograde cerebral perfusion group (P =.04)., Conclusions: These findings suggest that enhanced cranial hypothermia is the major beneficial factor of retrograde cerebral perfusion when careful attention is paid to its implementation.

Objective: Fulminant early-onset neonatal pneumonia is associated with ascending intrauterine infection (IUI), prematurity, persistent pulmonary hypertension (PPHN), and septicemia. Nitric oxide (NO) as an inflammatory mediator is included in antimicrobial defense and has a role in pathogenesis of septic shock. The aim was to study the role of inflammatory NO in neonatal pneumonia., Methods: Lungs from 36 autopsies were studied: 12 had fulminant early-onset neonatal pneumonia, 5 pneumonia of later onset, and 19 controls had similar gestational and postnatal age. In addition, airway specimens from 21 intubated newborns were analyzed: 7 with fulminant early-onset pneumonia, 7 apparently noninfected infants born prematurely attributable to IUI, and 7 premature infants of similar gestation. Specimens were analyzed for inducible NO synthase (NOS2) and nitrotyrosine, an indicator of NO toxicity. The degree of staining was analyzed., Results: In fulminant pneumonia, alveolar macrophages (AM) showed significantly less NOS2 immunoactivity than the controls. In the airway specimens, the infants with fulminant pneumonia 0 to 2 days after birth had significantly lower intracellular NOS2 and nitrotyrosine and significantly lower interleukin-1beta and surfactant protein-A than apparently noninfected IUI infants. NOS2 and the other indices increased significantly during the recovery., Conclusions: For the first time, we report NOS2 expression by macrophages from human neonates. In fulminant early-onset neonatal pneumonia, delayed production rather than excess of pulmonary inflammatory NO is associated with severe symptoms.

Background: Deep hypothermic circulatory arrest is an effective method of cerebral protection, but it is associated with long cardiopulmonary bypass times and coagulation disturbances. Previous studies have shown that retrograde cerebral perfusion can improve neurologic outcomes after prolonged hypothermic circulatory arrest. We tested the hypothesis that deep hypothermic retrograde cerebral perfusion could improve cerebral outcome during moderate hypothermic circulatory arrest., Methods: Twelve pigs (23-29 kg) were randomly assigned to undergo either retrograde cerebral perfusion (15 degrees C) at 25 degrees C or hypothermic circulatory arrest with the head packed in ice at 25 degrees C for 45 minutes. Flow was adjusted to maintain superior vena cava pressure at 20 mm Hg throughout retrograde cerebral perfusion. Hemodynamic, electrophysiologic, metabolic, and temperature monitoring were carried out until 4 hours after the start of rewarming. Daily behavioral assessment was performed until elective death on day 7. A postmortem histologic analysis of the brain was carried out on all animals., Results: In the retrograde cerebral perfusion group, 5 (83%) of 6 animals survived 7 days compared with 2 (33%) of 6 in the hypothermic circulatory arrest group. Complete behavioral recovery was seen in 4 (67%) animals after retrograde cerebral perfusion but only in 1 (17%) animal after hypothermic circulatory arrest. Postoperative levels of serum lactate were higher, and blood pH was lower in the hypothermic circulatory arrest group. There were no significant hemodynamic differences between the study groups., Conclusions: Cold hypothermic retrograde cerebral perfusion during moderate hypothermic circulatory arrest seems to improve neurologic outcome compared with moderate hypothermic circulatory arrest with the head packed in ice.

Objective: To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants., Study Design: Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored., Results: Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar., Conclusion: A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.