Severe Ventricular Dilatation Research Articles

Elevated CA 125 and ascites: not always malignancy

We present two clinical cases from a single institution where a final diagnosis of cardiac failure was made following the initial finding of ascites and an elevated CA 125 level. In both cases gynaecological malignancy was initially suspected. Following negative confirmatory tests for gynaecological malignancy, echocardiography was undertaken. Patient 1 had severe right ventricular dilatation and dysfunction. Patient 2 had biventricular dysfunction with pulmonary hypertension. Both patients responded to standard therapy for heart failure, including loop diuretics.

No Additive Effect of Passive Containment Surgery in Patients With Aortic Regurgitation and Left Ventricular Dilation

After valve replacement in patients with aortic regurgitation short-term and long-term improvement of left ventricular function are related to early reduction of left ventricular dilatation. This case-control study was conducted to investigate the potential beneficial effects by concomitant application of the Acorn Cor Cap Cardiac Support Device (Acorn Cardiovascular Inc, St. Paul, MN) on reduction of ventricular dilatation in patients with aortic regurgitation and advanced ventricular dilatation undergoing aortic valve replacement. Of ten patients with longstanding aortic regurgitation and ventricular dilatation subjected to aortic valve replacement using mechanical valve prostheses, five were in addition subjected to application of the Cardiac Support Device (Acorn). Cardiac function and dimensions were measured by echocardiography preoperatively and 3 and 12 months postoperatively. After aortic valve replacement, there was a rapid and sustained decrease in end-diastolic and end-systolic diameters (before operation 72 +/- 4 and 54 +/- 8 mm, to 54 +/- 10 and 40 + 11 mm at 3 months; and 53 +/- 9 and 35 +/- 6 mm, 12 months after operation). This did not differ after Cardiac Support Device (Acorn) application (before operation 74 +/- 1 and 56 +/- 5 mm; 52 +/- 8 and 39 +/- 9 mm, 3 months after operation; and 54 +/- 6 and 39 +/- 8 mm, at 12 months). The left ventricular ejection fraction remained unchanged in both groups. Application of the Acorn Cor Cap Cardiac Support Device in patients with aortic regurgitation and severe ventricular dilatation does not influence reverse remodeling or cardiac function compared with aortic valve replacement alone.

Diffusion-weighted imaging evaluation of subtle cerebral microstructural changes in intrauterine fetal hydrocephalus

Hydrocephalus is an important etiological factor in neurological decline. With the advent of fetal ultrasound, fetal hydrocephalus is now more frequently detected than in the past. Ultrasonography (USG) provides information on general morphology, but microstructural changes that may play a prognostic role are beyond the resolution of that technique. These changes may theoretically be revealed by diffusion-weighted magnetic resonance imaging (DW-MRI). In this study, our preliminary findings of DW-MRI on the hydrocephalic fetuses are presented. Twelve fetuses with fetal USG diagnosis of hydrocephalus were investigated using a 1.5-T MR scanner. In addition to conventional techniques, DWI was performed. It was obtained using a single-shot echo-planar imaging sequence (TR/TE: 4393/81 ms; slice thickness: 5 mm; interslice gap: 1 mm; FOV: 230 mm; matrix size: 128x256; b values: 0 and 1000 s/mm2). Apparent diffusion coefficient (ADC) values were measured in the white matter of the periventricular frontal and occipital lobes, basal ganglia, thalamus, centrum semiovale and cerebrospinal fluid in the lateral ventricle. These values were compared with the normal prenatal ADC values from a radiological study published in the literature. All fetuses had moderate or severe bilateral supratentorial ventricular dilatation that was compatible with hydrocephalus. On conventional T1- and T2-weighted imaging, cerebral parenchyma had normal signal pattern and ADC values were significantly lower than those reported for fetuses with normal brain. These values were lower in hydrocephalic fetuses with statistical significance (P<.05-.01). DWI is a sensitive technique to investigate cerebral microstructure. The reduction in cerebral blood flow and alterations in cerebral energy metabolism in cases with hydrocephalus have been shown before. Changes in cerebral blood flow and energy metabolism, as a consequence of cerebral compression, may occur in hydrocephalus. Elevated ventricular pressure may cause cerebral ischemia. The anaerobic glycolysis seen in the hydrocephalic brain tissue by increasing the lactate concentration and intracellular fluid flux may be the reason for the reduced ADC values in hydrocephalic fetuses. However, long-term prospective trials on the correlation of ADC values and neurological outcome are necessary to exploit the full benefit of that novel technique.

Predictors of Nocturnal Oxygen Desaturation in Pulmonary Arterial Hypertension

Background:Sleep may be associated with significant respiratory compromise in patients with lung disease and can result in hypoxia. In patients with pulmonary arterial hypertension (PAH), nocturnal desaturation may not be reflected in daytime evaluations of oxygenation and can lead to worsening pulmonary hemodynamics. The study was conducted to determine the prevalence and significance of nocturnal oxygen desaturation in patients with PAH.Methods:A cross-sectional study conducted at the Cleveland Clinic. Patients were followed up at our institution except for the overnight oximetry study done at home. Data regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary function, and functional capacity were collected.Results:Forty-three patients (mean age, 47.9 ± 13.5 years [± SD]; 36 women and 7 men) underwent nocturnal oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated with connective tissue diseases (12%). The majority of patients were New York Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%) spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%. Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002). Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular resistance. On echocardiography, desaturators were more likely to have moderate or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only one patient had significant sleep apnea.Conclusions:Nocturnal hypoxemia is common in PAH patients and correlates with advanced pulmonary hypertension and right ventricular dysfunction. Approximately 60% patients without exertional hypoxia had nocturnal desaturation. Overnight oximetry should be considered in the routine workup of PAH patients who do not demonstrate exertional desaturation.

Interstitial remodeling in β1-adrenergic receptor transgenic mice

BackgroundInhibition of proteolytic MMP activity could be a therapeutic approach to prevent ventricular dilatation by diminishing collagen matrix turnover and interstitial fibrosis. We investigated the time-course of MMP/TIMP activity during transition from hypertrophy to ventricular dilatation in transgenic mice with myocyte overexpression of the human β1-adrenergic receptor (β1TG). These β1TG mice were studied at 3 (normal function), 5 (hypertrophy) and 12 (ventricular dilatation) months of age compared to age-matched controls (WT).MethodsPicro Sirius red staining and real-time PCR were performed for total collagen and for collagen type I and III quantification, respectively. MMP-activity assays (zymography), immunoblotting and real-time PCR experiments were done for gelatinase- (MMP-2, -9), collagenase- (MMP-1, -13), membrane-type MMP- (MT1- MMP; MMP-14) and TIMP expression measurements. To investigate β1-integrin activity, integrin-linked kinase (ILK) expression was measured by immunoblotting.ResultsCompared to WT with normal cardiac function, interstitial collagen type I and III mRNA and protein expression increased 3.6-fold in β1TG at 5 months of age with moderate fibrosis and cardiomyocyte hypertrophy and 17-fold in β1TG at 12 months of age with severe fibrosis and ventricular dilatation. Protein expression of the collagenases MMP-1 and -13 as well as the gelatinase proMMP-2 increased in the β1TG group with cardiac hypertrophy. Maximal activity of the gelatinase MMP-2 (3.5-fold vs.WT) was measured in β1TG at 12 months of age with severe fibrosis and ventricular dilatation, accompanied by coexpression of MT1- MMP (3.8-fold vs.WT) colocalized to the cell membranes.ConclusionThese data provide evidence that sympathetic overactivation can trigger interstitial matrix remodeling and fibrosis by induction of MMP/TIMP activity. In particular gelatinolytic MMP-2 activity accompanies ventricular dilatation and the development of heart failure.

PERIPHERAL PULMONARY ARTERY STENOSIS IN A FOUR‐MONTH‐OLD WEST HIGHLAND WHITE TERRIER

A 4-month-old West Highland White Terrier was evaluated for dyspnea. Severe cardiac silhouette enlargement was present radiographically. Severe right ventricular hypertrophy and dilation with a dilated pulmonary trunk and a stenosis of the right pulmonary artery were diagnosed via echocardiography. Additional areas of peripheral pulmonary artery stenosis were diagnosed with nonselective computed tomography (CT) angiography and selective fluoroscopic angiography. Balloon dilation therapy was unsuccessful and the imaging findings were confirmed at necropsy.

Right ventricular restoration during pulmonary valve implantation in adults with congenital heart disease☆

Pulmonary regurgitation may cause progressive right ventricular dilatation and dysfunction in adult patients previously repaired for right ventricular outflow tract obstruction (RVOTO), and who require subsequent valve implantation for relief of these symptoms. Right ventricular recovery after pulmonary valve implantation (PVI) may be closely linked to the functional importance of the structural presence of an aneurysm or akinetic segment in the RVOT area. To test this concept, the impact of the right ventricular restoration with a new surgical ventriculoplasty technique is evaluated following pulmonary valve implantation in patients with severe pulmonary regurgitation and right ventricular dilatation. Sixteen patients with severe pulmonary valve regurgitation (PVR) and right ventricular dilatation with RVOT aneurysm underwent right ventricular remodelling since January 2002. Each underwent preoperative evaluation by Doppler echocardiography, magnetic resonance imaging (MRI), and right ventricular myocardial acceleration during isovolumic contraction (IVC). The surgical procedure included pulmonary valve implantation and RVOT restoration achieved by removal of the aneurysm tissue, coupled with a ventriculoplasty to reduce volume, accomplished by creating a satisfactory RVOT dimension by placing with 2-0 Gortex suture to allow acceptance of a 26 Hegar dilator to avoid restriction. Thirteen associate surgical procedures were added in nine patients. All patients survived the operative procedure and underwent a 16-month follow-up interval. A reduction of cardio thoracic index and a clinical improvement occurred in each patient. Significant reduction of RVEDV and RVESV and increased right ventricular ejection fraction was observed, and IVC changed from 0.7+/-0.5 m/s2 to 1.3+/-0.6 m/s2 in the 13 patients that underwent MRI and IVC during the preoperative control interval and 6 months after the procedure. This preliminary database implies that the right ventricular restoration is a simple and effective procedure, and introduces a structural component that should be added during pulmonary valve implantation in patients with severe right ventricular dilatation and underlying aneurysm or akinesia of the right ventricular outflow tract.

Neonatal antecedents for cerebral palsy in extremely preterm babies and interaction with maternal factors

Background Preterm delivery is associated with an increased risk of cerebral palsy (CP). The greatest risk is for infants born <28 weeks' gestation. Aims To identify significant neonatal risk factors for CP and explore the interactions between antenatal and neonatal risk factors, among extremely preterm infants of 27 weeks' gestation or less. Study Design Nested case control design. Methods Infants born between 1989 and 1996, at 24–27 weeks' gestation, were evaluated: 30 with CP at 2 years corrected age and 120 control infants matched for gestation age. Neonatal variables were compared using matched analyses with the interaction between antenatal and neonatal factors being examined using logistic regression analyses. Results Risk factors for CP on matched analyses included patent ductus arteriosus requiring surgical ligation, peri-intraventricular haemorrhage, moderate to severe ventricular dilatation, periventricular leukomalacia (PVL) and need for home oxygen. Independent neonatal predictors were ventricular dilatation (OR 7.3; 95% CI 1.6, 32.3), PVL (OR 29.8; 95% CI 5.6, 159.1) and home oxygen use (OR 3.4; 95% CI 1.2, 9.4). No interaction terms in the logistic models were significant between the previously identified pregnancy risk factors of absence of antenatal steroids and intrauterine growth restriction and the neonatal risk factors. Conclusions PVL is the most powerful independent predictor of CP in extremely preterm infants of 27 weeks' gestation or less and appears to be uninfluenced by antenatal factors.

Novel troponin T mutation in familial dilated cardiomyopathy with gender-dependant severity

Mutations in sarcomeric proteins can lead to either hypertrophic or dilated cardiomyopathy depending on their effects on the structural and functional properties of the contractile unit of the heart. Mutations in cardiac troponin T, which binds the calcium-responsive troponin complex to α-tropomyosin, have been shown to result in cardiac hypertrophy or cardiac dilatation and heart failure, depending on the nature of the specific mutation. In this study, we report the identification of a novel cardiac troponin T mutation (A171S) leading to dilated cardiomyopathy and sudden cardiac death. In contrast to prior described mutations, the A171S mutation results in a significant gender difference in the severity of the observed phenotype with adult males (over 20 years of age) demonstrating more severe ventricular dilatation [left ventricular end diastolic dimension (LVEDD) 7.1 vs. 5.1 cm; P=0.01, t test] and left ventricular dysfunction [left ventricular shortening fraction (LVSF) 21 vs. 34%; P=0.04, t test] than adult females. The described mutation substitutes a hydrophilic amino acid for a hydrophobic one in a highly conserved domain involved in the interaction between troponin T and α-tropomyosin. Interestingly, four previously described mutations within 12 amino acids of A171 lead to a hypertrophic phenotype, suggesting that further characterization of the functional consequences of the A171S mutation may lead to a better understanding of the pathophysiology of DCM and of the functional differences between HCM- and DCM-causing mutations in cardiac troponin T.

Implantable Cardioverter-Defibrillators in patients with arrhythmogenic right ventricular Dysplasia/Cardiomyopathy

ObjectivesThe aim of this study was to assess the outcome of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients treated with an implantable cardioverter-defibrillator (ICD). BackgroundArrhythmogenic right ventricular dysplasia/cardiomyopathy is associated with tachyarrhythmia and an increased risk of sudden death. MethodsThis study included 42 ARVD/C patients with ICDs (52% male, age 6 to 69 years, median 37 years) followed at our center. ResultsMean follow-up was 42 ± 26 months (range 4 to 135 months). Complications associated with ICD implantation included need for lead repositioning (n = 3) and system infection (n = 2). During follow-up, one patient died of a brain malignancy and one had heart transplantation. Lead replacement was required in six patients as a result of lead fracture and insulation damage (n = 4) or change in thresholds (n = 2). During this period, 33 of 42 (78%) patients received a median of 4 (range 1 to 75) appropriate ICD interventions. The median period between ICD implantation and the first firing was 9 months (range 0.1 to 66 months). The ICD firing storms were observed in five patients. Inappropriate interventions were seen in 10 patients. Predictors of appropriate firing were induction of ventricular tachycardia (VT) during electrophysiologic study (EPS) (84% vs. 44%, p = 0.024), detection of spontaneous VT (70% vs. 15%, p = 0.001), male versus female gender (91% vs. 65%, p = 0.04), and severe right ventricular dilation (39% vs. 0%, p = 0.013). Using multivariate analysis, VT induction during EPS was associated with increased risk for firing in ARVD/C patients; odds ratio 11.2 (95% confidence interval 1.23 to 101.24, p = 0.031). ConclusionsPatients with ARVD/C have a high arrhythmia rate requiring appropriate ICD interventions. The ICD therapy appears to be well tolerated and important in the management of patients with ARVD/C.

Fetal open spina bifida: a natural history of disease progression in utero.

To determine the natural history of the prenatal development of ventriculomegaly and talipes in fetuses with open spina bifida. All fetuses with isolated open spina bifida and managed at our center between January 1996 and March 2000 were retrospectively evaluated. Ultrasonographic images and reports were reviewed from examinations performed every 3 to 4 weeks from the time of diagnosis to delivery for lesion level and type, ventriculomegaly (defined as an atrial width of > or =10 mm), and lower extremity appearance. Of the 53 pregnancies identified, 20 (38%) were electively terminated. In the 33 ongoing gestations, the lesions ranged from lower thoracic to sacral; 79% were characterized as meningomyeloceles and 21% as myeloschises. Fifty-five percent (n = 18) had ventriculomegaly at diagnosis (early onset, mean gestational age at diagnosis 22 +/- 5 weeks), 33% (n = 11) subsequently developed ventriculomegaly (late onset, mean 29 +/- 6 weeks), and 12% (n = 4) had normal ventricle size at the last sonogram before birth (mean 38 +/- 1 weeks). The ventricular size prior to delivery was significantly smaller with late-onset ventriculomegaly than with early-onset: 15 +/- 4 mm versus 28 +/- 10 mm, (p = 0.001). Only 6% (n = 2) had talipes at the initial sonogram, and 18% (n = 6) were subsequently determined to have talipes (mean 30 +/- 6 weeks). Most fetuses with open spina bifida develop ventriculomegaly, and the majority do so by 21 weeks' gestation. Fetuses that develop ventriculomegaly later in gestation have less severe ventricular dilation at birth. In contrast, a minority of fetuses have congenital talipes, and because most cases develop after 20 weeks, they are not predicted by early midtrimester sonographic evaluation.

Pediatric lung transplant: do primary pulmonary hypertension patients have worse outcome?

High mortality risk has been reported for primary pulmonary hypertension (PPH) pts undergoing lung transplantation (LTx). Do PPH children have worse outcomes after LTx than cystic fibrosis (CF) children? All pediatric PPH pts undergoing LTx at our institution were compared to CF pts undergoing LTx in the same period. Data collected: demographics, echocardiograms, ischemic times, cardiopulmonary bypass times (CPB), perioperative and 1-year survival. From 1994-2002, 10 PPH children (3M:7F; mean age at Tx 13.7 ± 3.4 years) underwent LTx. Seven were on IV prostacyclin and 3 took oral beraprost prior to Tx. There were 5 living donor double lobar lung (LDL) Txs and 5 cadaveric double LTxs. Prior to Tx, all PPH pts had severe right ventricular and right atrial dilatation with pancaking of the left ventricle. Mean tricuspid regurgitation gradient prior to Tx was 102.5 ± 18.4 mmHg (range 74-140 mm Hg). Six pts were NYHA Class III and 4 were NYHA Class IV. Mean PPH ischemic times were 148.1 ± 83.4 min (range 52.5- 294 min). Mean CPB times were 139.9 ± 40.6 min (range 85-214 min). 9 PPH pts survived the perioperative period (90%); 1 pt expired from non-specific graft failure. Of the 9 surviving pts, 1 pt is <6 months post-Tx and 8 pts have survived >1 year (100%). During the same period, 41 CF pts (22M:19F; mean age at Tx 14.9 ± 3.5 years) were transplanted. There were 34 LDL and 7 cadaveric LTxs. Mean CF ischemic times were 99.7 ± 52.6 min (range 44.5-249 min). Mean CPB times were 124.2 ± 36.2 min (range 75-260 min). Of 41 CF pts, 38 survived the perioperative period (93%). One-year CF Tx survival was 92%. There was no difference between groups in age (p = 0.33), gender distribution (p = 0.29), CPB time (p = 0.25), perioperative mortality (p = 1.0), or 1-year survival (p = 1.0). There was a significant difference in ischemic times (p = 0.02) and type of Tx surgery (p = 0.04). We conclude that pediatric PPH pts have similar perioperative and 1-year survival compared to CF pts undergoing LTx. Our findings support lung transplantation as a viable therapeutic option for pediatric PPH pts who fail to respond to medical therapy.

Right ventricular dysfunction and pulmonary valve replacement after correction of tetralogy of fallot

Background. Correction of tetralogy of Fallot often leads to pulmonary regurgitation, sometimes warranting pulmonary valve replacement, for which indications and timing to achieve optimal results are not yet clear. This retrospective study describes follow-up and reinterventions in our tetralogy of Fallot population. Methods. Review of all consecutive patients operated on for tetralogy of Fallot between 1977 and 2000 was conducted. Included are date and type of repair, Doppler echocardiography (two-dimensional echocardiography), electrocardiographs, reoperations, and physical condition. Results. Total repair was performed in 171 patients at a mean age 1.9 ± 2.5 years, follow-up time counted 9.6 ± 7.0 years. Right ventriculotomy was used in 92%, and transatrial ventricular septal defect closure was used in 8%; 74% received a transannular outflow patch. Twenty-year survival was 91%. Last follow-up electrocardiographs showed right bundle branch block in 67% and serious arrhythmias in 11%. Two-dimensional echocardiography demonstrated severe pulmonary insufficiency and dilated right ventricle in 31% and 38%, respectively, increasing with postrepair age ( p < 0.001). Poor clinical condition (New York Heart Association class II+) and echocardiographic proof of right atrial dilatation ( p = 0.012) and arrhythmias ( p = 0.03) were significantly associated. Furthermore, the influence of residual hemodynamic lesions, such as a remaining ventricular septal defect or pulmonary stenosis, or right ventricular dilatation was important ( p = 0.04). Reintervention was necessary in 32 patients (19%; 10-year freedom, 83%), including angioplasty for residual stenosis and pulmonary valve replacement. At a mean age of 9.2 years after correction, 14 patients received a homograft, and 2 patients received a heterograft. In 7 patients the right ventricle returned to normal dimensions and symptoms disappeared. The incidence of right ventricular dilatation was considerably higher ( p = 0.020) in patients with a transannular patch; the transatrial approach showed the opposite ( p = 0.03), and patients presented with lower QRS duration ( p = 0.007), although no difference could be found between survival after both surgical techniques. Effects of early timing (correction < 6 months) on right ventricular dysfunction could not be established. Conclusions. Severe right ventricular dilatation and pulmonary regurgitation secondary to outflow tract repair in tetralogy of Fallot are frequently occurring sequelae developing slowly over time. Indications for pulmonary valve replacement remain controversial because echocardiographic findings or arrhythmias are not always accompanied by deterioration of clinical condition. However, right atrial dilatation and additional hemodynamic lesions demand increased vigilance. Transatrial repair is associated with a favorable outcome.

Modern treatment of pulmonary embolism.

Modern treatment of acute pulmonary embolism requires rapid and accurate diagnosis followed by risk stratification to devise an optimal management strategy. Patients at low risk have good outcomes simply with intensive anticoagulation treatment. Higher-risk patients may require more aggressive intervention with thrombolysis or embolectomy. Clinical risk factors for an adverse outcome include increasing age, cancer, congestive heart failure, systemic arterial hypotension, chronic obstructive pulmonary disease and right ventricular dysfunction. A promising approach is the Geneva Prognostic Score, which is based upon a rapid clinical assessment. On physical examination, signs of right ventricular failure, including distended jugular veins and a right-sided S3 gallop, should be looked for. The electrocardiogram may show evidence of right ventricular strain with a new right bundle branch block or T wave inversion in leads V1-V4. The troponin level may be elevated as a marker of cardiac injury and right ventricular microinfarction, even in the absence of coronary artery disease. The most useful imaging marker of high risk is the presence of moderate or severe right ventricular dilatation and hypokinesis on the echocardiogram, especially with progressively worsening right ventricular function despite intensive anticoagulation treatment. Patients at high risk should be considered for thrombolytic therapy or embolectomy rather than management with anticoagulation therapy alone. Special care must be taken to avoid thrombolytic therapy among patients who might be susceptible to intracranial haemorrhage. Intracranial haemorrhage reached a surprisingly high rate of 3.0% in the International Cooperative Pulmonary Embolism Registry of 2,454 prospectively evaluated acute pulmonary embolism patients at 52 hospitals in seven countries. An alternative approach to patients at high risk is a catheter-based or open surgical embolectomy. It is crucial to refer these patients as quickly as possible, rather than delaying intervention until cardiogenic shock has ensued. Fortunately the current tools for risk stratification provide an "early window" for prognostication and can help the coordination of a definitive treatment plan with optimal results.

Hidrocefalia crónica del adulto. Reto diagnóstico y terapéutico

To describe the main clinical features of the different conditions which present as chronic hydrocephaly, emphasising the diagnosis and treatment.In the study of any dementia syndrome, normotensive hydrocephaly (HN) is of particular interest since this condition may be treated and cured. However, prediction of which cases will benefit from surgery is one of the most important aspects of diagnosis. The development of paraclinical investigations of the dynamics of cerebrospinal fluid (CSF) has led to great advances in the management of these chronic forms of hydrocephaly, since they are the best parameters for prognosis when deciding whether to insert a by pass. The treatment of post traumatic hydrocephaly has also benefited from these studies, since the cases of simple atrophy may now be distinguished from those which follow a clinical course similar to HN. Recently, two types of hydrocephaly have been identified as being very different from the typical forms. These are external hydrocephaly, in which CSF accumulates in the convexity of the cerebral hemispheres, and long term ventriculomegaly, in which severe ventricular dilation is accompanied by cognitive alterations and features of acute hydrocephaly.Treatment of each of these conditions is a challenge. Therefore careful analysis of the clinical features, imaging studies and CSF dynamics is essential when deciding whether or not to use by pass treatment.

Heme Oxygenase-1 Protects the Heart

The seminal discovery of nitric oxide (NO) in the 1980s unraveled the novel concept that an endogenous production of a gaseous substance such as NO can impart diverse and critical functional effects on a wide spectrum of biological and pathological processes. Intense investigations in the chemistry and biology of NO have led to numerous fruitful discoveries, enhancing our understanding of many disease processes including cardiovascular disorders. Interestingly, though, we have known for a longer period of time that there exists another gaseous molecule, carbon monoxide (CO), which can be generated endogenously. The heme oxygenase (HO) enzyme system generates the majority of endogenous CO.1,2 Since the biochemical isolation of the HO enzyme in 1968, much of the focus of HO research has been in the study of HO in heme metabolism based on the known fact that the HO enzyme serves as the rate-limiting enzyme in the degradation of heme. However, in recent years, as a result of the emerging role of HO in a variety of biological processes, interest in HO has continued to grow beyond its role in heme metabolism and has expanded into many scientific disciplines. The recent characterization of the HO enzyme system in yeast, prokaryotic bacterial system, and plants further highlights the functional importance of a highly conserved enzyme throughout the evolution of living organisms. HO catalyzes the first and rate-limiting step in the degradation of heme to yield equimolar quantities of biliverdin IXa, CO, and iron1,2 (Figure). Biliverdin is subsequently converted to bilirubin via the action of biliverdin reductase, and free iron is promptly sequestered into ferritin. Three isoforms of HO exist; HO-1 is highly inducible whereas HO-2 and HO-3 are constitutively expressed.1,2 Heme, a major substrate of HO-1, and a variety of nonheme agents including heavy metals, cytokines, hormones, endotoxin, and …

Increase in bilirubin levels of patients with obstructive sleep apnea in the morning--a possible explanation of induced heme oxygenase-1.

In the absence of heme oxygenase-1 (HO-1), which catalyzes the oxidation of heme to generate carbon monoxide and indirect bilirubin, hypoxia induces severe right ventricular dilation and infarction. Despite severe hypoxemia during sleep, patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) rarely die during sleep. We hypothesized that apnea-related hypoxemia would induce HO-1 and increase bilirubin levels in the morning in OSAHS patients. Therefore, bilirubin levels in OSAHS patients were analyzed before and after nasal continuous positive airway pressure (nCPAP) therapy. Bilirubin levels in the afternoon before sleep and in the morning immediately after sleep were determined before and after nCPAP treatment. University Hospital in Kyoto, Japan. The subjects were 22 patients with OSAHS (mean (SEM) apnea and hypopnea index of 60 (5)) who were treated with nCPAP and 13 controls. N/A. Before nCPAP treatment, total after-sleep bilirubin level was significantly higher than the pre-sleep level (p<0.0001). The difference between the serum indirect bilirubin levels in the morning versus in the previous afternoon [D-(M-A)-IB] decreased significantly with nCPAP treatment (p<0.01). The magnitude of decrease in D-(M-A)-IB after nCPAP treatment correlated significantly with changes in the percent time spent with arterial O2 saturation below 90% (r=0.44; p=0.04) and 85% (r=0.49; p=0.02), respectively, during sleep after nCPAP treatment. The increase in bilirubin level by HO-1 might protect OSAHS patients from disorders related to hypoxemia.

Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome

To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n = 33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n = 69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function.

Anaesthetic management of caesarean section in a patient with a permanent pacemaker and severe bilateral ventricular dilatation

A 33-year-old primigravida presented at 32 weeks gestation with increasing shortness of breath related to left ventricular failure. She had severe bilateral ventricular dilatation of unknown aetiology. An urgent caesarean section was required when she failed to improve on medical therapy, and for this she requested general anaesthesia. The patient had a permanent pacemaker for congenital complete heart block and Harrington rods for kyphoscoliosis. In view of the cardiac problems we transferred the patient to our cardiac unit and performed the procedure with full invasive haemodynamic monitoring. An alfentanil based modified rapid sequence induction resulted in stable maternal haemodynamics. The 2.2 kg male neonate initially required ventilation for 12 h, but then made a good recovery along with his mother.

Indications for shunting in patients with idiopathic normal pressure hydrocephalus presenting with dementia and brain atrophy (atypical idiopathic normal pressure hydrocephalus).

The indications for shunt operation in patients with idiopathic normal pressure hydrocephalus accompanied by brain atrophy (atypical idiopathic normal pressure hydrocephalus: AINPH) were investigated in 25 patients who satisfied the diagnostic criteria and underwent ventriculoperitoneal (VP) shunting. All patients had no apparent history of intra- or extracranial disease; dementia and gait disturbance as the main complaints; moderate to severe cerebral atrophy and ventricular dilatation and at least periventricular low density around the anterior horn on computed tomography; normal cerebrospinal fluid (CSF) pressure and filling of ventricles or cortical surface space with contrast medium at 24 hours on cisternography. The 15 male and 10 female patients were aged 47-83 years (mean 60.4 years). VP shunting was effective in 12 improved patients and not effective in 13 unimproved patients according to NPH grading. Pathological pressure wave on epidural pressure monitoring was observed in eight of 12 improved patients, but none of 13 unimproved patients. CSF outflow resistance was 35.33 +/- 11.16 mmHg/ml/min in improved patients and 9.12 +/- 3.51 mmHg/ml/min in unimproved patients. Preoperative serum alpha-1-antichymotrypsin value (alpha-1-ACT) was 42.02 +/- 8.64 mg/dl in improved patients and 61.72 +/- 11.03 mg/dl in unimproved patients. Alpha-1-ACT over 55 mg/dl occurred only in unimproved patients. Cerebral arteriovenous difference of oxygen content value (c-AVDO2) before and after surgery was 6.34 +/- 0.9 ml% and 5.91 +/- 0.78 ml% in improved patients and 4.75 +/- 1.85 ml% and 4.81 +/- 1.73 ml% in unimproved patients, respectively. The two cases with preoperative c-AVDO2 value over 8.5 ml% were both unimproved. Mean cerebral blood flow value before and after surgery was 23.51 +/- 4.20 ml/100 g/min and 45.22 +/- 8.11 ml/100 g/min in improved patients and 21.77 +/- 5.12 ml/100 g/min and 24.82 +/- 4.97 ml/100 g/min in unimproved patients, respectively. Cerebral atrophy in improved patients is caused by a cerebral circulation disturbance defined as a cerebral blood flow of penumbra or more due to cerebral arteriosclerosis, etc. A flow-chart of indications of shunt surgery for AINPH was prepared based on the results of the present study.