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.

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.

Decreasing postoperative cognitive deficits after heart surgery: protocol for a randomized controlled trial on cognitive training.

BACKGROUND: The occurrence of postoperative cognitive deficits, especially after heart surgery, has been demonstrated in several studies. These deficits can clearly be noticed by the patients and by their close relatives in daily life. Furthermore, postoperative cognitive deficits can decrease quality of life in social functioning and earning capacity. The aim of this study is to investigate whether early postoperative cognitive training can reduce subjective and objective postoperative cognitive deficits. METHODS: The proposed study is a multicenter, two-arm, randomized controlled trial involving 144 elderly patients undergoing elective heart-valve surgery with extracorporeal circulation. Patients will be assigned to either a training group or a control group. The intervention involves paper-and-pencil-based cognitive training, which is conducted for 36 min over a period of 18 days. The training starts about 1 week after surgery and is carried out during the hospitalized rehabilitation phase. The control group will not receive cognitive training or a placebo intervention. A detailed assessment of psychological functions and health-related quality of life prior to surgery at discharge from rehabilitation and 3 and 12 months after discharge will be performed. The primary outcome of this trial is the training effect on objective cognitive functions at discharge from rehabilitation. Secondary outcomes are the training effect on objective and subjective cognitive functions (3 and 12 months after discharge), depression, health-related quality of life, and the impact of perioperative cerebral ischemia on the training effect. Perioperative cerebral ischemia will be measured with postoperative magnetic resonance imaging including diffusion-weighted sequences. DISCUSSION: Should it be shown that our cognitive training can improve postoperative cognitive deficits and quality of life, one possibility could be to integrate this intervention into early rehabilitation. Furthermore, we hope that the investigation of perioperative ischemia by diffusion-weighted magnetic resonance imaging will improve our understanding of neurobiological factors influencing the course of postoperative cognitive plasticity. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00015512. Retrospectively registered on 21 September 2018.

Biomarkers of Hand Osteoarthritis Are Detectable after Mechanical Exercise.

BACKGROUND: Hand osteoarthritis (OA) is one of the most common joint diseases, but studies on biomarkers are rare. The aim of this explorative study was (a) to evaluate potential biomarkers of hand OA, (b) to identify an optimal time point to sample venous blood, and (c) to correlate biomarker levels with radiological and clinical scores. METHODS: Four female cohorts were investigated. One with a more Heberden-accentuated OA and one with a more Bouchard-accentuated hand OA, and two symptom-free control groups aged 20-30 or 50-75 years. The venous blood was sampled before and at eight time points after mechanical exercise of the OA hand. X-rays of OA hands were assessed using the Kellgren and Lawrence as well as Kallman scores. Participants were evaluated clinically using the AUSCAN™ Index, visual analog scale (VAS), and Health Assessment Questionnaire (HAQ). Serum levels of seven biomarkers were measured by ELISA. RESULTS: The concentrations of CPII, COMP, IL-15, sVCAM-1, NGAL, and PIIANP were significantly increased within 15 min after exercise. PIIANP was markedly elevated in the Heberden-accentuated OA group as compared to both control groups, but did not correlate with any radiological or clinical score. Analysis of the probabilistic index further revealed that CPII can distinguish between Bouchard's OA and premenopausal controls whereas COMP can discriminate between Bouchard's and Heberden's OA. CONCLUSIONS: This study demonstrates that even previously undetectable biomarkers can be quantified in serum after mechanical exercise. Future larger studies are needed to determine specificity and sensitivity of these markers and their ability to diagnose even pre-radiological OA.

Aquaporin-4 autoantibodies increase vasogenic edema formation and infarct size in a rat stroke model.

BACKGROUND: Neuromyelitis optica (NMO) is an autoimmune disorder of the central nervous system, which is characterized by autoantibodies directed against the water channel aquaporin-4 (AQP4). As one of the main water regulators in the central nervous system, APQ4 is supposed to be involved in the dynamics of brain edema. Cerebral edema seriously affects clinical outcome after ischemic stroke; we therefore aimed to investigate whether NMO-antibodies may exert the same functional effects as an AQP4-inhibitor in-vivo in acute ischemic stroke. METHODS: Sixteen male Wistar rats were randomized into two groups twice receiving either purified NMO-IgG or immune globulin from healthy controls, 24 hours and 30 minutes before middle cerebral artery occlusion (MCAO) was performed. T2-weighted MRI was carried out 24 hours after MCAO. RESULTS: MRI-examination showed a significant increase of infarct size in relation to the cerebral hemisphere volume with NMO-IgG treated animals (27.1% ± 11.1% vs. 14.3% ± 7.2%; p < 0.05) when corrected for the space-occupying effect of vasogenic edema formation and similar results without edema correction (34.4% ± 16.4% vs. 17.5% ± 9.3%; p < 0.05). Furthermore, T2-RT revealed a significant increase in cortical brain water content of the treatment group (19.5 ms ± 9.7 ms vs. 9.2 ms ± 5.2 ms; p < 0.05). CONCLUSIONS: These results support the functional impact of NMO-antibodies and also offer an in-vivo-applicable animal model to investigate the properties of AQP4 in ischemic stroke.

Detection of myocardial injury by CMR after transcatheter aortic valve replacement.

BACKGROUND: Myocardial injury after transcatheter aortic valve replacement (TAVR) is common, but its cause and relationship to the extent of myocardial tissue loss remain unclear. OBJECTIVES: This study sought to examine the incidence and degree of ischemic myocardial damage using cardiac magnetic resonance imaging and myocardial biomarkers in patients undergoing TAVR. METHODS: Patients with severe aortic stenosis (n = 61) underwent cardiac magnetic resonance imaging before and after TAVR for the assessment of new myocardial injury. High-sensitivity cardiac troponin T and creatine kinase-myocardial band were measured before and at 24, 48, and 72 h after TAVR. RESULTS: After TAVR, new myocardial late enhancement (LE) with an ischemic pattern occurred in 11 patients (18%), with a mean mass of 3.7 g (interquartile range: 1.2 to 6 g) or 1.8% (interquartile range: 1.3% to 4.1%) of the left ventricular mass. Patients with new LE had a decreased left ventricular function (ejection fraction: pre, 55.5 ± 14.1% vs. post, 45.3 ± 14.9%; p = 0.001). In patients without new LE, no differences were observed (ejection fraction: pre, 53.9 ± 17.3% vs. post, 54.6 ± 16.3%; p = NS) after TAVR. CONCLUSIONS: New ischemic-type myocardial LE after TAVR can be observed in a notable proportion of patients and is assumed to be of embolic origin. Patients with new LE feature a significant decrease in left ventricular function at discharge.

Cortisol awakening and stress response, personality and psychiatric profiles in patients with takotsubo cardiomyopathy.

OBJECTIVE: Alterations in cortisol awakening and stress responses (CAR, CSR) are sensitive markers for the basal activity and responsiveness of the hypothalamus-pituitary-adrenal axis (HPAA) in psychopathological conditions. We investigated whether patients with takotsubo cardiomyopathy (TTC) differ in these markers when compared with non-ST-segment elevation myocardial infarction (NSTEMI) patients and healthy controls. METHODS: 19 female TTC patients were compared with 20 female NSTEMI patients and with 20 healthy women, matched by age and index event date. Salivary sampling indicated cortisol release, questionnaires assessed personality, life events, chronic stress and psychiatric symptoms. RESULTS: The groups did not differ relevantly in their basal HPAA activity, psychiatric or personality profiles. Despite increased heart rates in response to stress (median difference (MDdiff)=3.5, p=0.002) and higher nervousness scores (MDdiff=-3.0, p=0.024), TTC patients revealed a blunted CSR with a medium effect compared to the controls (MDdiff=-3.2 nmol/L, p=0.022, r=0.36); even when controlled for prestress cortisol differences (p=0.044, r=0.33). In comparison with NSTEMI patients, no significant differences in CSR (MDdiff=-1.9 nmol/L, p=0.127, r=0.25) or nervousness (MDdiff=2.0, p=0.107) can be observed. Stressful life events, for example, traumatic experiences, occurred more often in TTC (42%) than in NSTEMI patients and controls (both 10%, p=0.031). CONCLUSIONS: In this small exploratory trial, a trend for a blunted CSR and high incidences of stressful life events were observed in TTC patients. If these results can be confirmed in larger studies, chronic stress and the inhibitory influence of cortisol on catecholamine release might be significant for the pathogenesis of TTC.

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.

MR, CT, and PET imaging in pericardial disease.

Although echocardiography remains the standard diagnostic tool for identifying pericardial diseases, procedures with better delineation of morphology and heart function are often required. The pericardium consists of an inner visceral (epicardium) and outer parietal layer (pericardium), which constitute for the pericardial cavity. Pericardial effusion can occur as transudate, exudate, pyopneumopericardium, or hemopericardium. Potential causes are inflammatory processes, that is, pericarditis due to autoimmune or infective reasons, neoplasms, irradiation, or systemic disorders, chronic renal failure, endocrine, or metabolic diseases. Pericardial fat can mimic pericardial effusion. Using various image-acquisition sequences, MRI allows identifying and separating fluid and solid structures. Fast spin-echo T1-weighted sequences with black-blood preparation are favourably used for morphological evaluation. Fast spin-echo T2-weighted sequences, particularly with fat saturation, and short-tau inversion-recovery sequences are useful to visualize oedema and inflammation. For further tissue characterization, delayed inversion-recovery imaging is used. Therefore, image acquisition is performed at 5-20 min subsequent to contrast agent administration, the so-called technique of late gadolinium enhancement. Ventricular volumes and myocardial mass can be assessed accurately by steady-state free-precession sequences, which is required to measure cardiac function and ventricular wall stress. Constrictive pericarditis usually results from chronic inflammatory processes leading to increased stiffness, which impedes the slippage of both pericardial layers and thereby the normal cardiac filling. CT imaging can favourably assess pericardial calcification. Thus, MR and CT imaging allow a comprehensive delineation of the pericardium. Superior to echocardiography, both methods provide a larger field of view and depiction of the complete chest including abnormalities of the surrounding mediastinum and lungs. PET provides unique information on the in vivo metabolism of 18-fluorodeoxyglucose that can be superimposed on CT findings and is useful for identifying inflammatory processes or masses, for example neoplasms. These imaging techniques provide advanced information of anatomy and cardiac function to optimize the pericardial access, for example by the AttachLifter system, for diagnosis and treatment.

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.

MEDAFI-Trial (Micro-embolization during ablation of atrial fibrillation): comparison of pulmonary vein isolation using cryoballoon technique vs. radiofrequency energy.

AIMS: Cerebral embolism is a possible serious complication during catheter ablation of atrial fibrillation (AF). The purpose of this prospective pilot study was to analyse the incidence and possible impact of cryo ablation on cerebral lesions and possible differences to radiofrequency (RF) ablation during pulmonary vein isolation (PVI). METHODS AND RESULTS: Pulmonary vein isolation was performed in 89 patients, either with the cryoballoon technique (n = 45) or with RF ablation (n = 44). Phenprocoumon was stopped 3 days before intervention and replaced by subcutaneous low-molecular-weight heparin. During the catheter procedure, an infusion of unfractionated heparin was maintained to achieve an activated clotting time (ACT) of > 300 s. Cerebral magnetic resonance imaging scans were performed 1 day before and after PVI, and at 3-month follow-up. Chronic lesions were observed in 11 patients (12.3%) before PVI without statistically significant difference between the two groups. None of the patients had neurological symptoms during or following the procedure. Seven patients (7.9%) developed acute lesions 1 day after PVI, without statistically significant difference between the group treated by cryoenergy (8.9%) and RF ablation (6.8%). Patients with acute lesions were significantly older compared with those without acute cerebral lesions. No additional cerebral lesions during follow-up were observed. CONCLUSION: A considerable portion of patients with AF but without any neurological symptoms had chronic cerebral lesions before PVI. Additional acute lesions could be added after the procedure. Both ablation techniques showed additional cerebral acute lesions with no neurological symptoms after PVI.

Neuropsychological decline after catheter ablation of atrial fibrillation.

BACKGROUND: Cerebral embolic events represent recognized side effects after catheter ablation in the treatment of recurrent atrial fibrillation (AF). OBJECTIVE: The study was performed to analyze the neuropsychological outcome and to detect new embolic ischemic brain lesions after therapeutic left atrial catheter ablation of AF. METHODS: We enrolled 23 patients with recurrent AF who underwent elective circumferential pulmonary vein isolation. The primary endpoint was the neuropsychological outcome 3 months after intervention in contrast to the results of non-AF controls (n = 23) without ablation and in covariance of baseline performance. Cerebral diffusion-weighted magnetic resonance imaging (DWI) was performed in 21 AF patients at baseline, 2-4 days, and 3 months after intervention. RESULTS: In 3/21 patients (14.3%), new ischemic lesions were detected on DWI shortly after intervention. In one patient, a territorial middle cerebral artery infarct occurred with severe clinical symptoms. The other two patients represented clinically silent small lesions. In contrast to the control group and in covariance of baseline performance, the ablation group showed worse neuropsychological outcome in verbal memory (one of five cognitive domains) with an effect size of d = 0.93[t (.05; 42) = -3.53; P < .001; false discovery rate (FDR)(crit) ≤ .01]. CONCLUSION: Adverse neuropsychological changes after left atrial catheter ablation are verifiable in verbal memory and, conjoined with ischemic brain lesions on DWI, might represent cerebral side effects of this procedure.

Evaluation of the middle cerebral artery occlusion techniques in the rat by in-vitro 3-dimensional micro- and nano computed tomography.

BACKGROUND: Animal models of focal cerebral ischemia are widely used in stroke research. The purpose of our study was to evaluate and compare the cerebral macro- and microvascular architecture of rats in two different models of permanent middle cerebral artery occlusion using an innovative quantitative micro- and nano-CT imaging technique. METHODS: 4h of middle cerebral artery occlusion was performed in rats using the macrosphere method or the suture technique. After contrast perfusion, brains were isolated and scanned en-bloc using micro-CT (8 mum)3 or nano-CT at 500 nm3 voxel size to generate 3D images of the cerebral vasculature. The arterial vascular volume fraction and gray scale attenuation was determined and the significance of differences in measurements was tested with analysis of variance [ANOVA]. RESULTS: Micro-CT provided quantitative information on vascular morphology. Micro- and nano-CT proved to visualize and differentiate vascular occlusion territories performed in both models of cerebral ischemia. The suture technique leads to a remarkable decrease in the intravascular volume fraction of the middle cerebral artery perfusion territory. Blocking the medial cerebral artery with macrospheres, the vascular volume fraction of the involved hemisphere decreased significantly (p < 0.001), independently of the number of macrospheres, and was comparable to the suture method. We established gray scale measurements by which focal cerebral ischemia could be radiographically categorized (p < 0.001). Nano-CT imaging demonstrates collateral perfusion related to different occluded vessel territories after macrosphere perfusion. CONCLUSION: Micro- and Nano-CT imaging is feasible for analysis and differentiation of different models of focal cerebral ischemia in rats.

Combined contrast-enhanced ultrasound and rt-PA treatment is safe and improves impaired microcirculation after reperfusion of middle cerebral artery occlusion.

In monitoring of recanalization and in sonothrombolysis, contrast-enhanced ultrasound (CEUS) is applied in extended time protocols. As extended use may increase the probability of unwanted effects, careful safety evaluation is required. We investigated the safety profile and beneficial effects of CEUS in a reperfusion model. Wistar rats were subjected to filament occlusion of the right middle cerebral artery (MCA). Reperfusion was established after 90 minutes, followed by recombinant tissue-type plasminogen activator (rt-PA) treatment and randomization to additional CEUS (contrast agent: SonoVue; 60 minutes). Blinded outcome evaluation consisted of magnetic resonance imaging (MRI), neurologic assessment, and histology and, in separate experiments, quantitative 3D nano-computed tomography (CT) angiography (900 nm(3) voxel size). Nano-CT revealed severely compromised microcirculation in untreated animals after MCA reperfusion. The rt-PA partially improved hemispheric perfusion. Impairment was completely reversed in animals receiving rt-PA and CEUS. This combination was more effective than treatment with either CEUS without rt-PA or rt-PA and ultrasound or ultrasound alone. In MRI experiments, CEUS and rt-PA treatment resulted in a significantly reduced ischemic lesion volume and edema formation. No unwanted effects were detected on MRI, histology, and intracranial temperature assessment. This study shows that CEUS and rt-PA is safe in the situation of reperfusion and displays beneficial effects on the level of the microvasculature.

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.

Evaluation of methods to predict early long-term neurobehavioral outcome after coronary artery bypass grafting.

Postoperative cognitive decrease (POCD) represents the most frequent complication in modern cardiac surgery. The application of easily assessable surrogate parameters that predict long-term POCD at early time points is tempting. The aim of the present study was to analyze the predictive value of cerebral biomarkers, diffusion-weighted magnetic resonance imaging (DWI), and cognitive bedside testing after coronary artery bypass grafting (CABG). From 106 patients who underwent elective CABG, blood samples were drawn for the measurement of protein S100B and neuron-specific enolase release at baseline, at the end of surgery, and 48 hours afterward. Cerebral DWI was carried out before and 2 to 4 days after surgery. Cognitive functioning was assessed before, 2 to 4 days (bedside testing) after, and 3 months after CABG. On DWI, lesions were detected in 15.1% of patients. Biomarker levels and the presence of acute ischemic lesions on DWI were not associated with long-term POCD. Early POCD was correlated with 3-month POCD (r = 0.46, p <0.001). Ninety-one percent of patients who had shown moderate to severe POCD (<-1.5 z scores) in the early phase still had decreased memory functioning at 3 months compared to baseline (likelihood ratio 5.23). Early POCD was asserted as the only predictor for long-term POCD in a stepwise multiple linear regression model (R(2) = 0.20, p <0.001), excluding age, length of surgery, aortic clamping and cardiopulmonary bypass duration, the number of anastomoses, and postoperative neuron-specific enolase and S100B levels. In conclusion, the results show that in contrast to biomarkers, DWI, age, or intraoperative variables, early neuropsychological bedside testing predicts long-term POCD after CABG with acceptable accuracy.

Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study.

Cartilage defects occur in approximately 12% of the population and can result in significant function impairment and reduction in quality of life. Evidence for the variety of surgical treatments available is inconclusive. This study aimed to compare the clinical outcomes of patients with symptomatic cartilage defects treated with matrix-induced autologous chondrocyte implantation (MACI or microfracture (MF). Included patients were >or= 18 and

Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial.

AIMS: The purpose of the study was to investigate whether intra-operative filter devices protect the brain during coronary artery bypass grafting (CABG) and to determine the impact of solid and gaseous micro-emboli on neuropsychological functioning. METHODS AND RESULTS: Patients undergoing CABG received either an intra-aortic filter (Embol-X) (n = 43), designed to reduce solid micro-emboli, a dynamic bubble trap (DBT) (n = 50), designed to reduce gaseous micro-emboli, or no additional device (control group) (n = 50). Cognitive functioning was assessed before and 3 months after CABG. Micro-emboli signals (MES) were detected during surgery using transcranial Doppler (TCD) sonography. Cerebral magnetic resonance imaging (MRI) was carried out before and after surgery. Primary endpoint was the cognitive outcome of the filter groups compared with the controls. Analysis of covariance was performed using the post-operative cognitive test scores as continuous variables in covariance of the corresponding pre-operative scores. Secondary endpoints were the MES rates and the number of acute ischaemic lesions after CABG. Compared with the controls, cognitive functioning of the DBT group was better in executive functioning (t = 2.525, P = 0.0065) and verbal short-term memory (t = 2.420, P = 0.009). The Embol-X group did not perform better in any test. The total number of MES was lower in the DBT group (median 99, P = 0.0019), but not in the Embol-X group (median 162.5, P > 0.05), both compared with controls (median 164.5). After surgery, 17 patients displayed small ischaemic brain lesions on MRI with equal distribution between the groups. CONCLUSION: Gaseous micro-embolization contributes to neuropsychological decline, which is measurable 3 months post-operatively. No filter device could protect the brain during CABG completely. However, the use of the DBT tends to improve the cognitive outcome after CABG. Gas filters are recommendable for neuroprotection during cardiac surgery.