Hans Henrik Odland

Antioxidant activity in the newborn brain: a luciferase mouse model.

Introduction: Oxidative stress in the newborn period may cause cell injury and inflammation if the antioxidant capacity is insufficient. To monitor antioxidant and inflammatory activity we examined by in vivo imaging various strains of luciferase reporter mice whose light-emitting properties were regulated by response elements or complete promoters related to oxidative stress and/or inflammation. The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life. Methods: One mouse strain reports the activity of nuclear factor-ĸB (NF-ĸB) activity, a transcription factor essential for modulating inflammation, apoptosis, differentiation and cell growth. A second mouse strain reports on superoxide dismutase 1-promoter activity. A third strain reports the promoter activity of γ-glutamylcysteine synthetase, the rate limiting enzyme in glutathione production, and the last strain reports on antioxidant responsive element (ARE)/electrophil responsive element. Wild-type female mice mated with NF-ĸB mice were imaged through pregnancy to monitor intrauterine NF-ĸB activation. Results: Intrauterine NF-ĸB activity increased dramatically from day 17 towards labor. During the first 4 days of life luminescence measured was intense in all mice with distinct strain differences. All strains had high luminescence levels at day 1 and a considerably lower level at day 10. Conclusion: This model allows investigation of the transcriptional regulation of key proteins related to oxidative stress and inflammation in pregnancy and the first days of life. With very little stress to the newborn animals genetic activity can be monitored day by day.

Atrioventricular Valve Annulus Velocity and Acceleration during Global Hypoxia in Newborn Pigs – Assessment of Myocardial Function

Background: Global hypoxia may affect regions of the neonatal heart during systole and diastole differently. Objective: In the first study, the aim was to assess longitudinal myocardial function in newborn pigs during global hypoxia and recovery. In the second study, invasive hemodynamic data were evaluated and compared with tissue velocities and acceleration. Methods: Myocardial Doppler measurements of velocity and acceleration in the atrioventricular valve annuli during global hypoxia were made. Results: In the first experiment, systolic velocity (S), early diastolic velocity (E’) and peak systolic acceleration (pSac) decreased during hypoxia. S, pSac and E’mva (mitral valve annulus) recovered after reoxygenation, while E’septal and E’tva (tricuspid valve annulus) did not. Isovolumic acceleration (IVA) did not reflect systolic dysfunction. In the second experiment, Smva and pSacmva declined during hypoxia similarly to maximum dP/dT. E’mva and E’tva were correlated with τ and both changed parallel to minimum dP/dT. In the TVA maximum dP/dT and pSactva did not change, while Stva declined. By correcting for heart rate the pattern of alteration in S and pSac became comparable to the changes in E’. Conclusion: Tissue Doppler velocity in systole, diastole and acceleration during rapid ejection reflect hemodynamic changes in the neonatal myocardium during global hypoxia and recovery. S and pSac reflect systolic function, while E’ correlates with τ and mirrors diastolic function.

Heart failure therapy in children

The most common reason for heart failure in children is volume overload secondary to a left-to-right shunt. Therefore, an accurate diagnosis with identification of possible surgical or interventional reactions should be the first priority. Medical therapy is mainly based on diuretics, angiotensin-converting enzyme inhibitors, cardiac glycosides and β-blockers. There are few prospective trials in pediatric cardiology, but the available data reach a similar conclusion to that of adults with heart failure. Diuretics are an important tool in patients with fluid retention, and angiotensin-converting enzyme inhibitors are helpful in patients with volume overload of the ventricles. Cardiac glycosides are still in use, but there is a trend toward primary use of diuretics. Angiotensin-converting enzyme inhibitors and β-blockers have been used successfully in the treatment of heart failure in children, but there are limited data on its efficacy.

High-resolution data assimilation of cardiac mechanics applied to a dyssynchronous ventricle

Computational models of cardiac mechanics, personalized to a patient, offer access to mechanical information above and beyond direct medical imaging. Additionally, such models can be used to optimize and plan therapies in-silico, thereby reducing risks and improving patient outcome. Model personalization has traditionally been achieved by data assimilation, which is the tuning or optimization of model parameters to match patient observations. Current data assimilation procedures for cardiac mechanics are limited in their ability to efficiently handle high-dimensional parameters. This restricts parameter spatial resolution, and thereby the ability of a personalized model to account for heterogeneities that are often present in a diseased or injured heart. In this paper, we address this limitation by proposing an adjoint gradient-based data assimilation method that can efficiently handle high-dimensional parameters. We test this procedure on a synthetic data set and provide a clinical example with a dyssynchronous left ventricle with highly irregular motion. Our results show that the method efficiently handles a high-dimensional optimization parameter and produces an excellent agreement for personalized models to both synthetic and clinical data.

Catheter-Based Closure of an Atrial Septal Defect in Scimitar Syndrome

We report a patient with abnormal systemic blood supply to the right lung and right-sided anomalous pulmonary venous drainage to the inferior vena cava (scimitar syndrome or pulmonary venolobar syndrome). In addition, she had an atrial septal defect, underdeveloped right pulmonary artery, an aberrant right bronchus, and tracheobronchomalacia. She improved markedly after palliative interventional closure of her atrial septal defect.

Fourteen-year-old boy with severe hypertension and monosymptomatic nocturnal enuresis (Discussion and Diagnosis)

DISCUSSION Most cases of confirmed childhood hypertension are secondary to other diseases and are renal in origin (1). Renovascular disease causes 5–10% of all childhood hypertension, with stenosis due to fibromuscular dysplasia being the most common cause (2). All children with hypertension who need more than one drug should be investigated for a renovascular cause (3). While renal artery stenosis in adults is usually located at the ostium, in children it can be located more peripherally, even in the segmental arteries, and easily missed during ultrasound examination (4). Surprisingly, the selective angiography in our patient revealed a small network of tortuous arteries in the lower part of the left kidney (Fig. 1). There was no sign of significant arteriovenous shunting or formation of aneurysms, but the findings were believed to represent a small, congenital, arteriovenous malformation (AVM). Arteriovenous malformations, arteriovenous fistulas, aneurysms or aberrant vessels all represent a heterogenous group of diseases and aetiologies. Congenital AVMs of the kidney are rare, with a prevalence of less than 1% among the general population. AVMs are direct communications between the renal arteries and veins, via enlarged, tortuous vascular spaces, and can sometimes be seen using Doppler sonography (5). Most AVMs remain asymptomatic, but haematuria, renin-induced hypertension, abdominal pain, affected kidney function, polyuria and electrolyte abnormalities have been described (6). The diagnosis can be difficult, as ultrasound, computed tomography and magnetic resonance imaging often are normal. Selective angiography remains the gold standard for diagnosis. There is one case report in the literature that describes the association between AVMs and polyuria. That patient had severe hypertension, polyuria and underwent nephrectomy (7). In our patient, a multidisciplinary team decision was made to perform an endovascular embolisation. After coiling of the small, tortuous arteries seen during diagnostic angiography, further arteries supplying the pathological network appeared (Fig. 2). Therefore, we performed more extensive coil embolisation than anticipated, resulting in devascularisation of approximately 50% of the left kidney. Our patient had earlier consulted doctors because of nocturnal enuresis, probably indicating polyuria, and he was still symptomatic when he presented with hypertension. His nocturnal enuresis ceased the day after embolisation and has, so far, not recurred. Studies in adults have shown that hypertension is related to nocturnal polyuria and has a prevalence of 50–70% (8,9). The mechanisms are unclear. Some studies have reported a positive relationship between the sodium renal excretion and blood pressure levels, thus ‘resetting’ the pressurenatriuresis curve (10). In addition, a diurnal variation in arginine vasopressin secretion has been shown to be positively correlated with hypertension (11). Several case reports describe malignant hypertension and polyuria in connection with renal artery stenosis (6,12,13). In our case, a small vessel malformation affecting a lower segment of the kidney was enough to cause symptomatic hypertension. The goal of embolisation is permanent occlusion of all feeders and the nidus of the AVM. Takabayashi et al. successfully embolised 30 cases of congenital AVM (14). At least 59% of patients with congenital AVM and hypertension responded to embolisation. It may take 2–3 months

Fourteen‐year‐old boy with severe hypertension and monosymptomatic nocturnal enuresis (Case Presentation)

CASE PRESENTATION A 14-year-old boy, with known monosymptomatic nocturnal enuresis, was presented with syncope after a head trauma while playing soccer and was found to be hypertensive. He had been playing soccer 6 days a week until admission and was in good physical condition, with normal weight and height (50th percentile). A year earlier, he had been seen at the outpatient clinic due to therapy-resistant enuresis, where they tried alarm, desmopressin, acupuncture and chiropractor treatment without success. His blood pressure had not been measured, and he had suffered from headaches and nausea for a year. On admission, his blood pressure was 154/86 (>95th percentile for height, sex and age). His hypertension was confirmed, with 24-h ambulatory blood pressure monitoring showing a mean blood pressure of 160/86 mmHg (>95th percentile for age, sex and height). Family history of hypertension, renal and cardiac disease was negative. Creatinine, electrolytes, endo-

A Centerline-Based Model Morphing Algorithm for Patient-Specific Finite Element Modeling of the Left Ventricle

Goal: Hexahedral automatic model generation is a recurrent problem in computer vision and computational biomechanics. It may even become a challenging problem when one wants to develop a patient-specific finite element (FE) model of the left ventricle (LV), particularly when only low resolution images are available. In the present study, a fast and efficient algorithm is presented and tested to address such a situation. Methods: A template FE hexahedral model was created for an LV geometry using a general electric ultrasound (US) system. A system of centerline was considered for this LV mesh. Then, the nodes located over the endocardial and epicardial surfaces are, respectively, projected from this centerline onto the actual endocardial and epicardial surfaces reconstructed from a patients US data. Finally, the position of the internal nodes is derived by finding the deformations with minimal elastic energy. This approach was applied to eight patients suffering from congestive heart disease. An FE analysis was performed to derive the stress induced in the LV tissue by diastolic blood pressure on each of them. Results: Our model morphing algorithm was applied successfully and the obtained meshes showed only marginal mismatches when compared to the corresponding US geometries. The diastolic FE analyses were successfully performed in seven patients to derive the distribution of principal stresses. Conclusion: The original model morphing algorithm is fast and robust with low computational cost. Significance: This low-cost model morphing algorithm may be highly beneficial for future patient-specific reduced-order modeling of the LV with potential application to other crucial organs.

Parametric ultrasound and fluoroscopy image fusion for guidance of left ventricle lead placement in cardiac resynchronization therapy

Abstract. Recent studies show that the response rate to cardiac resynchronization therapy (CRT) could be improved if the left ventricle (LV) is paced at the site of the latest mechanical activation, but away from the myocardial scar. A prototype system for CRT lead placement guidance that combines LV functional information from ultrasound with live x-ray fluoroscopy was developed. Two mean anatomical models, each containing LV epi-, LV endo- and right ventricle endocardial surfaces, were computed from a database of 33 heart failure patients as a substitute for a patient-specific model. The sphericity index was used to divide the observed population into two groups. The distance between the mean and the patient-specific models was determined using a signed distance field metric (reported in mm). The average error values for LV epicardium were −0.4±4.6 and for LV endocardium were −0.3±4.4. The validity of using average LV models for a CRT procedure was tested by simulating coronary vein selection in a group of 15 CRT candidates. The probability of selecting the same coronary branch, when basing the selection on the average model compared to a patient-specific model, was estimated to be 95.3±2.9%. This was found to be clinically acceptable.

Nicotine does not influence NF-κB activity in neonatal mice reoxygenated with room-air or 100% oxygen

Background: Nuclear factor kappa B (NF-κB) is considered an important mediator of inflamation, but is also important for developing organs and is constitutive active in neurons in the newborn brain. Objectives: We wanted to test the effects of preconditioning with nicotine on neonatal mice subjected to hypoxia and reoxygenated with either room-air or 100% oxygen. We hypothesized that nicotine would be neuroprotective and possibly reduce detrimental effects of 100% oxyegn on body organs. Methods: In this randomized study, we used neonatal transgenic NF-κB reporter mice that were preconditioned with nicotine or vector only prior to hypoxia, and then subjected to resuscitation with room-air or 100% oxygen. Results: We did not find any differences in NF-κB activity in whole body or in the brain of animals resuscitated with room-air or 100% oxygen. Resuscitation with 100% oxygen attenuated NF-kB activity when compared with resuscitation with room-air. However, when bioluminescence was properly corrected for body weight, the difference between room-air and 100% reoxygenation was no longer evident. Conclusions: Preconditioning with nicotine does not have any effect on NF-κB activity in body organs or in the brain of neonatal mice after hypoxia and resuscitation with either room-air or 100% oxygen. 100% oxygen did not alter NF-κB activity when compared to room-air resuscitation alone.