Aluminium Chloride instead of Ferric chloride for inducing superior sagittal sinus thrombosis to reduce ferromagnetic artifacts on MRI-imaging in experimental models.

Using ferric chloride (FeCl3) to induce experimental superior sagittal sinus (SSS) thrombosis might interfere with magnetic resonance imaging (MRI)-assisted visualization and evaluation of the thrombus, the brain parenchyma, and the quality of the occlusion. The aim of this study was to investigate whether aluminum chloride (AlCl3)-induced thrombosis of the SSS has comparable properties to those of FeCl3 without causing artifacts in MRI. SSS thrombosis was induced in 14 male Wistar rats by exposure of the SSS and subsequent topical application of a filter paper strip soaked in AlCl3 (n = 7) or FeCl3 (n = 7) over a period of 15 min. The animals with AlCl3-induced SSS thrombosis showed a constant and complete occlusion with in histological analysis large thrombi. Blood flow measurements indicated a significant reduction on the first and seventh postoperative day compared to preoperative measurements. MRI enabled visualization and subsequent evaluation of the thrombus and the surrounding parenchyma. In comparison, FeCl3-induced SSS thrombosis could not be evaluated by MRI due to artifacts caused by the paramagnetic properties and increased susceptibility of FeCl3. The occluded sinus and the surrounding area appeared hypointense. The quality of SSS occlusion by AlCl3 was comparable to that of FeCl3. AlCl3 therefore represents a significant alternative substance in experimental SSS thrombosis ideally suited for studies using MRI.

Patient-Reported Postoperative Neuropsychological Deterioration After Heart Valve Replacement and Coronary Artery Bypass Grafting.

Background: Postoperative cognitive decline (POCD) after cardiosurgical interventions are well described through objective psychometric tests. However, a patient's subjective perception is essential to clinical assessment and quality of life. This study systematically evaluated patient-reported POCD between subjects undergoing coronary artery bypass grafting and heart valve replacement. Methods: This study was a multicentre, prospective questionnaire survey conducted at the cardiac surgery departments at the Kerckhoff Clinic in Bad Nauheim and the University Hospital in Giessen, Germany. We included patients undergoing elective coronary artery bypass grafting (CABG), aortic valve replacement (AVR), mitral valve replacement or reconstruction (MVR), and combined surgery (CABG + valve replacement [VR]) with extracorporeal circulation. The Hospital Anxiety and Depression Scale, the Cognitive Failures Questionnaire (CFQ) for Self-assessment (CFQ-S), and the external assessment (CFQ-foreign [F]) were completed preoperatively, as well as at 3 and 12 months postoperatively. Results: A total of 491 patients were available for analyses (CABG = 182, AVR = 134, MVR = 93, CABG + VR = 82). POCD and postoperative depression increase (PODI) were observed for each surgical procedure. (At the 3-month follow-up: CFQ-S [CABG = 7.1%, AVR = 3.7%, MVR = 9.7%, CABG + VR = 9.8%]; CFQ-F [CABG = 9.9%, AVR = 9.7%, MVR = 9.7%, CABG + VR = 15.9%]; PODI [CABG = 7.7%, AVR = 9.7%, MVR = 6.5%, CABG + VR = 8.5%]. At the 12-month follow-up: CFQ-S [CABG = 6.6%, AVR = 7.5%, MVR = 15.1%, CABG + VR = 7.3%]; CFQ-F [CABG = 7.1%, AVR = 14.9%, MVR = 10.8%, CABG + VR = 9.8%]; PODI [CABG = 10.4%, AVR = 11.2%, MVR = 6.5%, CABG + VR = 4.9%]). No significant between-group effects were observed for the CFQ-S, CFQ-F, or the Hospital Anxiety and Depression Scale. Conclusions: For clinicians, paying attention to patients' self-reported experiences of reduced cognitive function and symptoms of depression following cardiac surgery is important. Such reporting is an indication that interventions such as cognitive training or psychotherapy should be considered.

Contexte: Le déclin cognitif postopératoire (DCPO) à la suite d'interventions de chirurgie cardiaque est bien décrit par des évaluations psychométriques objectives. Cependant, la perception subjective du patient est essentielle à l'évaluation clinique et à la qualité de vie. Cette étude visait à évaluer de façon systématique le DCPO déclaré par le patient chez des sujets ayant subi un pontage aortocoronarien ou une chirurgie valvulaire. Méthodologie: Cette étude prospective multicentrique par questionnaire a été menée aux services de chirurgie cardiaque de la clinique Kerckhoff de Bad Nauheim et de l'hôpital universitaire de Giessen, en Allemagne. Elle a porté sur des patients ayant subi un pontage aortocoronarien (PAC), un remplacement valvulaire aortique (RVA), un remplacement ou une reconstruction de la valvule mitrale (RVM) ou une chirurgie combinée (PAC et remplacement valvulaire [RV]) avec circulation extracorporelle, en situation non urgente. L'échelle d'évaluation de l'anxiété et de la dépression à l'hôpital (HADS), le questionnaire d'auto-évaluation des déficits cognitifs (CFQ-S) et le questionnaire d'évaluation externe des déficits cognitifs (CFQ-F) ont été remplis avant l'intervention chirurgicale, ainsi que 3 et 12 mois après la chirurgie. Résultats: Au total, les résultats de 491 patients étaient disponibles aux fins d'analyses (PAC = 182, RVA = 134, RVM = 93, PAC et RV = 82). Des cas de DCPO et une augmentation postopératoire des symptômes de dépression (APOD) ont été observés après chacune des interventions chirurgicales. (Lors du suivi après 3 mois : DCPO selon le CFQ-S [PAC = 7,1 %, RVA = 3,7 %, RVM = 9,7 %, PAC + RV = 9,8 %]; DCPO selon le CFQ-F [PAC = 9,9 %, RVA = 9,7 %, RVM = 9,7 %, PAC + RV = 15,9 %]; APOD [PAC = 7,7 %, RVA = 9,7 %, RVM = 6,5 %, PAC + RV = 8,5 %]. Lors du suivi après 12 mois : DCPO selon le CFQ-S [PAC = 6,6 %, RVA = 7,5 %, RVM = 15,1 %, PAC + RV = 7,3 %]; DCPO selon le CFQ-F [PAC= 7,1 %, RVA = 14,9 %, RVM = 10,8 %, PAC+ RV = 9,8 %]; APOD [PAC = 10,4 %, RVA = 11,2 %, RVM = 6,5 %, PAC + RV = 4,9 %]). Aucun effet intergroupe significatif n'a été observé relativement aux questionnaires CFQ-S et CFQ-F ou à l'échelle HADS. Conclusions: Il est important que les cliniciens portent attention aux déclarations des patients en ce qui concerne la diminution des fonctions cognitives et les symptômes de dépression à la suite d'une chirurgie cardiaque. De telles déclarations sont une indication que des interventions comme l'entraînement cognitif ou la psychothérapie doivent être envisagées.

The impact of postoperative cognitive training on health-related quality of life and cognitive failures in daily living after heart valve surgery: A randomized clinical trial.

BACKGROUND: Heart surgery is a risk factor for objectively and subjectively assessable postoperative cognitive decline (POCD), which is relevant for everyday life. The aim of this study was to investigate whether early postoperative cognitive training has an impact on health-related quality of life and cognitive failures in daily living after cardiac surgery. METHODS: The study was a two-arm, randomized, controlled, outcome-blinded trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation (ECC). Recruitment took place at the Departments of Cardiac Surgery of the Kerckhoff Clinic in Bad Nauheim (Germany) and the University Hospital in Giessen (Germany). The patients were randomized (1:1 ratio) to either a paper-and-pencil-based cognitive training group or a control group. We applied the Short Form Health Survey (SF-36) and the Cognitive Failures Questionnaire (CFQ) prior to surgery and 3 months after the cognitive training. Data were analyzed in a per-protocol fashion. RESULTS: Three months after discharge from rehabilitation, the training group (n = 31) showed improvement in health-related quality of life compared to the control group (n = 29), especially in role limitations due to emotional problems (U = -2.649, p = .008, η2  = 0.121), energy and fatigue (F[2.55] = 5.72, p = .020, η2  = 0.062), social functioning (U = -2.137, p = .033, η2  = 0.076), the average of all SF-36 factors (U = -2.374, p = .018, η2  = 0.094), health change from the past year to the present time (U = -2.378, p = .017, η2  = 0.094), and the mental component summary (U = -2.470, p = .013, η2  = 0.102). CONCLUSION: As our cognitive training has shown beneficial effects, this intervention could be a promising method to enhance health-related quality of life after cardiac surgery.

Increasing preoperative cognitive reserve to prevent postoperative delirium and postoperative cognitive decline in cardiac surgical patients (INCORE): Study protocol for a randomized clinical trial on cognitive training.

Introduction: Postoperative delirium (POD) and postoperative cognitive decline (POCD) can be observed after cardiosurgical interventions. Taken together, these postoperative neurocognitive disorders (PNCDs) contribute to increased morbidity and mortality. Preoperative risk factors of PNCD, such as decreased neuropsychometric performance or decreased cognitive daily activities, can be interpreted as reduced cognitive reserve. This study aims to build up cognitive reserves to protect against the development of PNCD through preoperative, home-based, cognitive training. Methods: The planned research project is a monocentric, two-arm randomized controlled intervention study involving 100 patients undergoing elective cardiac surgery with extracorporeal circulation. Patients will be assigned to a training group or control group. The intervention involves a standardized, paper-and-pencil-based cognitive training that will be performed by the patients at home for ~40 min per day over a preoperative period of 2-3 weeks. The control group will receive neither cognitive training nor a placebo intervention. A detailed assessment of psychological functions will be performed ~2-3 weeks before the start of training, at the end of the training, during hospitalization, at discharge from the acute clinic, and 3 months after surgery. The primary objective of this study is to investigate the interventional effect of preoperative cognitive training on the incidence of POD during the stay in the acute clinic, the incidence of POCD at the time of discharge from the acute clinic, and 3 months after surgery. Secondary objectives are to determine the training effect on objective cognitive functions before the surgery and subjective cognitive functions, as well as health-related quality of life 3 months after surgery. Discussion: Should it become evident that the use of our cognitive training can both reduce the incidence of POCD and POD and improve health-related quality of life, this intervention may be integrated into a standardized prehabilitation program.

Visual Hallucinations following Coronary Artery Bypass Grafting: A Prospective Study.

Background and Objectives: After major heart surgery, some patients report visual hallucinations that cannot be attributed to psychosis or delirium. This study aimed to investigate the hallucination incidence in patients after coronary artery bypass grafting with (on-pump) and without (off-pump) extracorporeal circulation. Materials and Methods: A total of 184 consecutive patients listed for elective on- or off-pump coronary artery bypass grafting were prospectively enrolled into the study. Preoperative baseline investigations 24-48 h before surgery (t0) and postoperative follow-up 24-48 h (t1) and 5-6 days (t2) after surgery included cognitive testing and a clinical visual acuity test (Landolt rings). Patients reporting visual hallucinations were interviewed using a structured survey to record the type, timing, duration, and frequency of their hallucinations. All the patients received a neurological examination and cranial magnetic resonance imaging if indicated. Results: Of the patients in the sample, 155 patients underwent on-pump bypass surgery, and 29 patients received off-pump surgery. Of these, 25 patients in the on-pump group, but none in the off-pump group, reported transient visual hallucinations (p = 0.020), which could not be attributed to stroke, delirium, psychosis, migraine, or severely impaired vision. Significant correlations were observed for the occurrence of visual hallucinations and the amount of nicotine consumption and aortic clamp/extracorporeal circulation time. Conclusions: Transient visual hallucinations occur in a noticeable proportion of patients after on-pump heart surgery. Knowledge of the phenomenon's benignity is important for patients to prevent anxiety and uncertainty and for treating physicians to avoid unnecessary medication and drug-induced delirium.

Effects of postoperative cognitive training on neurocognitive decline after heart surgery: a randomized clinical trial.

OBJECTIVES: Following cardiac surgery, postoperative cognitive decline (POCD) is a common complication that can impair the quality of life and increase mortality. The aim of this study was to investigate whether early postoperative cognitive training can decrease POCD after cardiac surgery. METHODS: The study was a multi-centred, two-arm, randomized (1:1 ratio), controlled trial involving older patients undergoing elective heart valve surgery with extracorporeal circulation. Recruitment took place at the Department of Cardiac Surgery of the Kerckhoff-Clinic in Bad Nauheim (Germany) and the University-Hospital in Giessen (Germany). The patients were randomized to either a paper-and-pencil-based cognitive training group or a standard rehabilitation care control group. The cognitive training started 1 week after surgery and lasted about 3 weeks until discharge from rehabilitation. To detect POCD, neuropsychological functions were assessed prior to surgery, upon discharge from rehabilitation (primary outcome), and 3 months after discharge (secondary outcome). Data were primarily analysed in a per-protocol fashion. RESULTS: The frequency of POCD at discharge from rehabilitation (training group, n = 37; control group, n = 44) was 50% in the control group and 19% in the training group (χ2[1] = 8.45, P = 0.004; odds ratio = 4.29, 95% confidence interval [1.56-11.80]). Three months after the cognitive training (training group, n = 33; control group, n = 34), POCD frequency was 29% in the control group and 6% in the training group (χ2[1] = 6.21, P = 0.013; odds ratio = 6.46, 95% confidence interval [1.29-32.28]). CONCLUSIONS: Since our cognitive training showed beneficial effects, it could be a promising method to prevent POCD.

Neuroprotective effects of dynamic bubble trap use in patients undergoing pulmonary endarterectomy: a two-arm randomized controlled trial.

BACKGROUND: During cardiosurgical procedures that use extracorporeal circulation (ECC), a variety of neurological complications can occur, and postoperative cognitive deficits remain an unsolved problem. Among the sources of these complications are intraoperatively detectable cerebral microemboli, which mainly consist of air. This study's purpose was to assess neuroprotective effects of reducing these gaseous microemboli using a dynamic bubble trap (DBT) in patients undergoing pulmonary endarterectomy (PEA) for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Patients undergoing PEA were randomly assigned to receive either a DBT (n=47) or no additional device (controls, n=46) during ECC. Neuropsychological testing was performed before and 3 months after PEA. The primary endpoint was cognitive improvement in the DBT group (n=29) compared with the control group (n=42). As secondary endpoint, ischemic brain micro-lesions were analyzed on postoperative days 6 through 10 using diffusion-weighted magnetic resonance imaging (MRI). RESULTS: Analysis of interaction effects revealed improved performance in visual long-term memory (P=0.008, η2=0.099), verbal long-term memory (P=0.030, η2=0.067), verbal short-term memory (P=0.014, η2=0.083), and attention and processing speed (P=0.043, η2=0.056) from pre- to post-testing in the DBT group compared to control group. In MRI, postoperative ischemic micro-lesions could only be detected in one patient; another patient suffered a severe bihemispheric embolic stroke. CONCLUSIONS: DBT positively influences memory function after PEA. This effect is most likely caused by the reduction of gaseous microemboli. TRIAL REGISTRATION: This study is registered in the German Clinical Trials Register, ID: DRKS00021499.

Neuroprotective mechanisms of erythropoietin in a rat stroke model.

OBJECTIVE: This study was designed to investigate the indirect neuroprotective properties of recombinant human erythropoietin (rhEPO) pretreatment in a rat model of transient middle cerebral artery occlusion (MCAO). METHODS: One hundred and ten male Wistar rats were randomly assigned to four groups receiving either 5,000 IU/kg rhEPO intravenously or saline 15 minutes prior to MCAO and bilateral craniectomy or sham craniectomy. Bilateral craniectomy aimed at elimination of the space-consuming effect of postischemic edema. Diagnostic workup included neurological examination, assessment of infarct size and cerebral edema by magnetic resonance imaging, wet-dry technique, and quantification of hemispheric and local cerebral blood flow (CBF) by flat-panel volumetric computed tomography. RESULTS: In the absence of craniectomy, EPO pretreatment led to a significant reduction in infarct volume (34.83 ± 9.84% vs. 25.28 ± 7.03%; p = 0.022) and midline shift (0.114 ± 0.023 cm vs. 0.083 ± 0.027 cm; p = 0.013). We observed a significant increase in regional CBF in cortical areas of the ischemic infarct (72.29 ± 24.00% vs. 105.53 ± 33.10%; p = 0.043) but not the whole hemispheres. Infarct size-independent parameters could not demonstrate a statistically significant reduction in cerebral edema with EPO treatment. CONCLUSIONS: Single-dose pretreatment with rhEPO 5,000 IU/kg significantly reduces ischemic lesion volume and increases local CBF in penumbral areas of ischemia 24 h after transient MCAO in rats. Data suggest indirect neuroprotection from edema and the resultant pressure-reducing and blood flow-increasing effects mediated by EPO.

Five-year follow-up of transvenous and epicardial left ventricular leads: experience with more than 1000 leads.

OBJECTIVES: Transvenous coronary sinus leads are considered to be the gold standard for cardiac resynchronization therapy (CRT). However, in patients with abnormal coronary vein anatomy, the epicardial leads can be an alternative. Data comparing durability and performance of these 2 lead types are limited. In order to provide clarity, we investigated patients receiving CRT system in our centre. METHODS: One thousand and fifty-three consecutive patients scheduled for CRT implantation were retrospectively analysed. From these, 895 received transvenous coronary sinus and 158 epicardial left ventricular (LV) leads. Lead-specific as well as LV functional parameters have been evaluated in 60 months' follow-up. RESULTS: Technical characteristics (pacing threshold, impedance and sensing) of both lead types remained stable during the whole observation period. Whereas an early revision (<6 month) was noted in 5.4% of transvenous leads, no reintervention has been necessary for epicardial leads. During the 5-year observation period, a lead revisions rate of 10.2% for transvenous leads and 1.9% for epicardial leads were detected. Regarding CRT efficacy, excellent results were achieved for both electrode types. In both groups, a statistically significant reduction of New York Heart Association class (2.85-2.13 and 2.96-2.09), increase in left ventricular ejection fraction (24.6-32.6% and 27.2-34.6%), reduction of left ventricular end-systolic diameter/left ventricular end-diastolic diameter and reduction in degree of mitral valve insufficiency could be observed over the time. CONCLUSIONS: Our data demonstrate safety and functional efficacy of both transvenous and epicardial leads. Moreover, in long-term follow-up, a commendable durability and performance were found for both lead types. Thus, epicardial leads represent a good alternative when transvenous implantation fails.

Explantation and reimplantation of a breast implant to facilitate minimally invasive mitral valve surgery and cryoablation of atrial fibrillation.

Clinicians can feel confident about performing mitral repair/replacement in patients who have previously undergone mammoplasty. It may also have applications in performing atrial septal defect closure, Maze procedures for atrial fibrillation, and tricuspid valve surgery in patients with breast implants.

Inter- and intra-rater reliability of computer-assisted planimetry in experimental stroke research.

BACKGROUND: Computer-assisted planimetry is widely used in experimental stroke research to assess the size of the ischemic lesion or hemispheric volume. NEW METHOD: Only insufficient data exist on the training required to achieve sufficient reliability in planimetry. Therefore, planimetry was performed over 15 months by two blinded raters who were initially inexperienced in the method. For inter-rater reliability, the hemispheric and lesional volume of 227 male Wistar Unilever rats subjected to middle cerebral artery occlusion were determined in diffusion- and T2-weighted sequences. For the intra-rater agreement, one investigator assessed the hemispheric and lesional volume in 87 T2-weighted sequences twice within a six-week interval. The correlation was calculated using Krippendorff's alpha and Bland-Altman plots illustrated the agreement. RESULTS: Inter-rater agreement increased during the first seven weeks and remained at high values (Krippendorff's alpha > 0.88). For intra-rater agreement, Krippendorff's alpha was 0.84 for hemispheric and 0.85 for lesional volume. The Bland-Altman plot indicated solid agreement between raters in the absence of systematic errors. COMPARISON WITH EXISTING METHODS: Simplified geometrical models or automated methods for planimetry can be used to determine lesional volume, but both approaches are inappropriate to assess hemispheric volume. CONCLUSION: Computer-assisted planimetry can be an appropriate method to determine hemispheric or ischemic lesion volume in rodents but requires a sufficiently long learning period of approximately two months. Even an experienced investigator can generate data with serious variation. Inter- and intra-rater-dependent bias should be considered during the design and performance of respective studies.

The Relevance of Postoperative Cognitive Decline in Daily Living: Results of a 1-Year Follow-up.

OBJECTIVES: Postoperative cognitive decline (POCD) has a perceivable influence on daily living and is noticed more often by close relatives than by patients themselves 3 months after aortic valve replacement. This study aimed to elucidate the longitudinal course of the subjective awareness of POCD. DESIGN: Follow-up of a prospective observational study. SETTING: A single cardiothoracic center in Germany. PARTICIPANTS: The study included 108 patients scheduled for elective aortic valve replacement surgery and 85 close relatives of the patients. INTERVENTIONS: In addition to conducting a neuropsychologic examination, the authors previously interviewed 82 patients with a Cognitive Failure Questionnaire for self-assessment (s-CFQ), and 62 relatives with the Cognitive Failure Questionnaire for others (f-CFQ) before and 3 months after surgery. Up until 12 months after surgery, the authors continuously interviewed additional patients (baseline and 3 months after surgery), thereby enlarging the original sample, and included the entire group (108 patients, 85 relatives) for the 12-month follow-up. RESULTS: The analysis showed that relatives (p = 0.026) and patients experienced patients' cognitive decline 3 months after surgery (p = 0.009). All changes still were observed in questions related to memory and attention. After 1 year, the s-CFQ no longer differed between baseline and postoperative assessment. Mean scores in the f-CFQ still were above baseline, barely missing statistical significance (p = 0.051). In patients with "change to worse" in the f-CFQ at 1-year follow-up, declining cognitive results in nonverbal learning (p = 0.021) could be observed 3 months postoperatively. Only a decrease in 3-month f-CFQ correlated with a decline in specific neuropsychologic tests 3 months after surgery. CONCLUSIONS: Contrary to the authors' previous results, the impact of POCD on daily living functions also was recognized by the patients themselves. The long-term influence and the associations between subjective deficits and psychometric cognitive measures seemed to be assessed more reliably by close relatives.

Off-pump transapical implantation of artificial neo-chordae to correct mitral regurgitation: the TACT Trial (Transapical Artificial Chordae Tendinae) proof of concept.

OBJECTIVES: The goal of this study was to evaluate the safety and performance of the NeoChord DS1000 system (NeoChord, Inc., Minneapolis, Minnesota). BACKGROUND: There is an increasing interest in transcatheter mitral valve (MV) treatment. The NeoChord DS 1000 system enables off-pump beating heart transapical MV repair with implantation of artificial neo-chordae. METHODS: Patients with severe mitral regurgitation (MR) due to isolated posterior prolapse were included in this TACT (Transapical Artificial Chordae Tendinae) trial. All patients were scheduled for off-pump transapical implantation of neo-chordae. RESULTS: Thirty patients at 7 centers were enrolled. Major adverse events included 1 death due to post-cardiotomy syndrome and concomitant sepsis and 1 minor stroke with the patient fully recovered at the 30-day follow-up visit. Additional patients experienced procedural major adverse events related to a reoperation or conversion to standard of care. Acute procedural success (placement of at least 1 neo-chord and reduction of MR from 3+ or 4+ to ≤2+) was achieved in 26 patients (86.7%). In 4 patients neo-chordae were not placed for technical and/or patient-specific reasons. These patients underwent intraoperative (3 patients) or post-operative (1 patient) standard MV repair. At 30 days, 17 patients maintained an MR grade ≤2+. Four patients who developed recurrent MR were successfully treated with open MV repair during 30-day follow-up. Results improved with experience: durable reduction in MR to ≤2+ at 30 days was achieved in 5 (33.3%) of the first 15 patients and 12 (85.7%) of the last 14 patients. CONCLUSIONS: Off-pump transapical implantation of artificial chordae to correct MR is technically safe and feasible; however, it yields further potential for improvement of efficacy and durability. (Safety and Performance Study of the NeoChord Device [TACT]; NCT01777815).

Impact of bubble size in a rat model of cerebral air microembolization.

BACKGROUND: Cerebral air microembolization (CAM) is a frequent side effect of diagnostic or therapeutic interventions. Besides reduction of the amount of bubbles, filter systems in the clinical setting may also lead to a dispersion of large gas bubbles and therefore to an increase of the gas-liquid-endothelium interface. We evaluated the production and application of different strictly defined bubble diameters in a rat model of CAM and assessed functional outcome and infarct volumes in relation to the bubble diameter. METHODS: Gas emboli of defined number and diameter were injected into the carotid artery of rats. Group I (n = 7) received 1800 air bubbles with a diameter of 45 µm, group II (n = 7) 40 bubbles of 160 µm, controls (n = 6) saline without gas bubbles; group I and II yielded the same total injection volume of air with 86 nl. Functional outcome was assessed at baseline, after 4 h and 24 h following cerebral MR imaging and infarct size calculation. RESULTS: Computer-aided evaluation of bubble diameters showed high constancy (group I: 45.83 µm ± 2.79; group II: 159 µm ± 1.26). Animals in group I and II suffered cerebral ischemia and clinical deterioration without significant difference. Infarct sizes did not differ significantly between the two groups (p = 0.931 u-test). CONCLUSIONS: We present further development of a new method, which allows reliable and controlled CAM with different bubble diameters, producing neurological deficits due to unilateral cerebral damage. Our findings could not display a strong dependency of stroke frequency and severity on bubble diameter.

Ultrasound destruction of air microemboli as a novel approach to brain protection in cardiac surgery.

OBJECTIVE: Evaluation of a novel approach to eliminate air microemboli from extracorporeal circulation via ultrasonic destruction. DESIGN: In vitro proof-of-concept study. SETTING: Research laboratory. PARTICIPANTS: None. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An extracorporeal circulation device was filled with human blood circulating at 3 L/min. Air bubbles were injected into the system. For bubble destruction, the blood in the tubing system was repeatedly insonated for 3 minutes using a therapeutic 60-kHz device, with variation of intensity and duty cycle settings, ranging from 0.2 W/cm² to 1.0 W/cm² and from duty cycle 60% to continuous wave (CW). Number and diameter of air microemboli were counted upstream and downstream of the ultrasound device by a 2-channel microemboli Doppler detector. For safety assessment, circulating blood was insonated continuously for 2 hours at 0.8 W/cm² CW and compared with circulation without insonation; and standard blood parameters were analyzed. Without treatment, 1,313 to 1,580 emboli were detected upstream, diameter ranging between 10 and 130 µm. Ultrasound treatment eliminated up to 87% of all detected bubbles in cw application (p<0.01) and showed comparable effects at intensities from 0.4 W/cm² to 1.0 W/cm² cw. Bubbles sized>15 µm almost were eliminated completely (p<0.001). Pulsed wave application rendered inferior results (p>0.05). No relevant changes of blood parameters were observed compared with control circulation. CONCLUSIONS: Ultrasound destruction of air emboli is a very efficient method to reduce number and size of emboli. Within the limits of safety assessment, the authors could not detect relevant side effects on standard blood parameters.

Subjective impairment after cardiac surgeries: the relevance of postoperative cognitive decline in daily living.

OBJECTIVES: Postoperative cognitive decline (POCD) is a frequent complication after cardiac surgeries. It remains unclear how relevant this decline in psychometric results is for daily life. The aim of the study was to assess cognitive failures, as seen by patients and close relatives, on a quantitative level. METHODS: In addition to an extensive neuropsychological test battery, we interviewed 82 patients with a modified version of the self-assessment cognitive failure questionnaire (s-CFQ) and 62 close relatives (mostly spouses) with the CFQ-for-others version (f-CFQ) before and 3 months after aortic valve replacement. The questionnaires evaluate the frequency of failures in daily living related to memory, attention, action and perception. RESULTS: POCD occurred in all tests that had been applied to assess declarative memory functions; the mean performance dropped from baseline in these tests (P-values ranging from 0.033 and <0.001). The s-CFQ did not differ between baseline and postoperative assessment [baseline: mean 37.60, standard deviation (SD) 14.38; post: mean 36.22, SD 12.29] (t(0.05, 76) = 1.17; P = 0.246). However, the assessment by others was worse in the f-CFQ after surgery (baseline: mean 8.02, SD 4.51; post: mean 9.58, SD 6.11) (t(0.05, 61) = 2.61; P = 0.012). All changes were observed in questions related to memory and attention failures only. Higher (worse) rates in f-CFQ change scores correlated with neuropsychological change scores, namely in pictorial memory (mistakes) (r = 0.35; P = 0.003) and word fluency (correct answers) (r = -0.29; P = 0.014). Additionally, those patients with worse f-CFQ change scores (>1 SD) from baseline had clearly worse outcomes in word fluency (t(0.05, 60) = 2.53; P = 0.007) and non-verbal learning (t(0.05, 60) = 2.66; P = 0.005). The effects remained significant when controlled for depression/anxiety scores. CONCLUSIONS: The result demonstrates that cognitive side-effects could have a perceivable impact on daily living functions. However, slight deficits are more realized by others than by the patients themselves. Correlations between ratings by others and psychometric cognitive measures indicate that assessment by others is more reliable than self-assessment.

Cognitive decline and ischemic microlesions after coronary catheterization. A comparison to coronary artery bypass grafting.

BACKGROUND: Postinterventional cognitive dysfunction (PICD) is a known complication of coronary artery bypass grafting (CABG). However, it is largely unknown whether PICD occurs after coronary catheterization. METHODS: Neuropsychologic data were obtained from 37 patients who received coronary catheterization and 47 patients who underwent elective CABG at baseline and 3 months after the interventions. The outcomes were contrasted to 33 healthy volunteers, using analysis of covariance with baseline scores as covariates. Cerebral magnetic resonance imaging with diffusion-weighted imaging (DWI) sequences was performed in 30 catheter and 39 CABG patients 2 to 4 days after the procedures. RESULTS: The rate of acute ischemic lesions amounted to 3.3% in the catheter group and to 17.9% in the CABG group. Postinterventional cognitive dysfunction was detected in 2 (of 10) tests in the catheter group as compared with the healthy controls (verbal memory: total recall, t = -2.61 (P = .005) and nonverbal memory, t = -2.60 [P = .005]). The CABG group showed PICD in 7 of 10 tests as compared with the healthy controls (statistics ranging from t = -1.95 [P = .027] to t = -5.14 [P < .001]). Scores of depression/anxiety and health-related quality of life were not associated with PICD (P > .05). CONCLUSIONS: As compared with CABG, PICD and cerebral lesions appear to be substantially milder after coronary catheter intervention, but not negligible.

A rat model for cerebral air microembolisation.

Subtle cerebral air microembolisation (CAM) is a typical complication of various medical interventions such as open heart surgery or angiography and can cause transient or permanent neurological and neuropsychological deficits. Evaluation of the underlying pathophysiology requires animal models that allow embolisation of air bubbles of defined diameter and number. Herein we present a method for the production of gas bubbles of defined diameter and their injection into the carotid artery of rats. The number of gas microemboli injected is quantified digitally using a high speed optical image capturing system and a custom-made software. In a first pilot study, 0, 50, 100, 400 and 800 gas bubbles of 160 microm in diameter were injected into the carotid artery of rats. Offline evaluation revealed a high constancy of the bubble diameters (mean 159.95+/-9.25 microm, range 144-188 microm) and the number of bubbles injected. First preliminary data indicate that with increasing number of bubbles embolised, more animals revealed neurological deficits and (particularly with higher bubble counts) brain infarctions on TTC-staining. Interestingly, also animals without overt infarcts on TTC-staining displayed neurological deficits in an apparently dose dependent fashion, indicating subtle brain damage by air embolism. In conclusion, the method presented allows injecting air bubbles of defined number and diameter into cerebral arteries of rats. This technique facilitates animal research in the field of air embolisation.

Edema formation in the hyperacute phase of ischemic stroke. Laboratory investigation.

OBJECT: Brain edema formation is a serious complication of ischemic stroke and can lead to mechanical compression of adjacent brain structures, cerebral herniation, and death. Furthermore, the space-occupying effect of edema impairs regional cerebral blood flow (rCBF), which is particularly important in the penumbra phase of stroke. In the present study, the authors evaluated the natural course of edema formation in the hyperacute phase of focal cerebral ischemia. METHODS: Middle cerebral artery occlusion (MCAO) or a sham procedure was performed in rats within an MR imaging unit (in-bore occlusion). Both pre- and postischemic images could be compared on a pixel-by-pixel basis. The T2 relaxation time (T2RT), a marker for brain water content, was measured in regions of interest. RESULTS: A significant increase in the T2RT was detectable as early as 20-45 minutes after MCAO. At this early time point the midline shift (MLS) amounted to 0.214 +/- 0.092 cm in the MCAO group and 0.061 +/- 0.063 cm in the sham group (p < 0.007). The T2RT and MLS increased linearly thereafter. Evans blue dye was intravenously injected in additional animals 20 and 155 minutes after MCAO. Extravasation of the dye was visible in all animals, indicating increased permeability of the blood-brain barrier. CONCLUSIONS: Vasogenic brain edema occurs much earlier than expected following permanent MCAO and leads to MLS and mechanical compression of adjacent brain structures. Since compression effects can impair rCBF, early edema formation can significantly contribute to infarct formation and thus represents a promising target for neuroprotection.