Cardiac Function in Brain Death, Usage of Advanced Hemodynamic Monitoring

Background: This study used advanced hemodynamic monitoring along with simultaneous echocardiography to assess donated heart function of brain death patients using advanced hemodynamic monitoring and its efficacy in organ donation. Methods: Forty-eight brain death patients who were candidates of heart donation on the basis of primary standard investigations were selected with purposive and convenient sampling methods. They were investigated with advanced hemodynamic monitoring after echocardiography and primary assessments and the gleaned data were recorded. Results: Echocardiography showed that LVS (left ventricle size) and LVF (left ventricle function) were normal in %100 and %87.5 of patients, respectively. LVEF (left ventricle ejection fraction) was <%50 in %12.5 and >%50 in %87.5 of patients. SVR was smaller than 1200 at the beginning of the study that reached %54.4 at the end of the study. CI (cardiac index) was < 2.4 in %16.7 of the patients at the onset of the study that reached %25 at the end. Reduction of CI and SVR in patients with EF <%50 was significantly higher than that in patients with EF>%50. Conclusion: Given the extensive pathological changes in the cardiovascular system exerted by brain death, advanced hemodynamic monitoring, if performed continually, can greatly aid in managing inotropic drugs in these patients, decision-making for managing intravascular volume, creating hemodynamic stability, and finally, preventing deterioration of function of the donated heart and loss of a donated organ.

Impact of ventricle size on neuropsychological outcomes in treated pediatric hydrocephalus: an HCRN prospective cohort study

OBJECTIVE In pediatric hydrocephalus, shunts tend to result in smaller postoperative ventricles compared with those following an endoscopic third ventriculostomy (ETV). The impact of the final treated ventricle size on neuropsychological and quality-of-life outcomes is currently undetermined. Therefore, the authors sought to ascertain whether treated ventricle size is associated with neurocognitive and academic outcomes postoperatively. METHODS This prospective cohort study included children aged 5 years and older at the first diagnosis of hydrocephalus at 8 Hydrocephalus Clinical Research Network sites from 2011 to 2015. The treated ventricle size, as measured by the frontal and occipital horn ratio (FOR), was compared with 25 neuropsychological tests 6 months postoperatively after adjusting for age, hydrocephalus etiology, and treatment type (ETV vs shunt). Pre- and posttreatment grade point average (GPA), quality-of-life measures (Hydrocephalus Outcome Questionnaire [HOQ]), and a truncated preoperative neuropsychological battery were also compared with the FOR. RESULTS Overall, 60 children were included with a mean age of 10.8 years; 17% had ≥ 1 comorbidity. Etiologies for hydrocephalus were midbrain lesions (37%), aqueductal stenosis (22%), posterior fossa tumors (13%), and supratentorial tumors (12%). ETV (78%) was more commonly used than shunting (22%). Of the 25 neuropsychological tests, including full-scale IQ (q = 0.77), 23 tests showed no univariable association with postoperative ventricle size. Verbal learning delayed recall (p = 0.006, q = 0.118) and visual spatial judgment (p = 0.006, q = 0.118) were negatively associated with larger ventricles and remained significant after multivariate adjustment for age, etiology, and procedure type. However, neither delayed verbal learning (p = 0.40) nor visual spatial judgment (p = 0.22) was associated with ventricle size change with surgery. No associations were found between postoperative ventricle size and either GPA or the HOQ. CONCLUSIONS Minimal associations were found between the treated ventricle size and neuropsychological, academic, or quality-of-life outcomes for pediatric patients in this comprehensive, multicenter study that encompassed heterogeneous hydrocephalus etiologies.

A Descriptive Study of Histopathological of Chronic Brain Ischemia of Rat Tissue

Worldwide, cerebrovascular accidents (stroke) are the second leading cause of death and the third leading cause of disability. However, not many the histopathological study of progression in chronic stroke has been published so far. This study gives the detail explanation of mechanism of recovery and might give the idea of new timeline when to set up the treatment to regenerate restoration of damaged cells. Fourteen male Wistar rats (15–20 weeks, weighing 250-400 g) were used in this study. Prior to 7 days of adaptation to the laboratory environment, rats were divided into four groups. Sham group (n=2), rats that sacrificied 4th week (n=2), 8th week (n=5), 12th week(n=5). 90 minutes temporary MCAO procedures were performed using the Indonesian modified technique. CD31 and Doublecortin markers were used to evaluate angiogenesis and neurogenesis. The results showed that ventricle size of ipsilateral brain was not so affected as in week 12th compared to 8th week. Gliosis as a response to damage to the central nervous system was more dense in week 12th as oppose to week 4th. Regarding angiogenesis and neurogenesis, there is significant improvement of angiogenesis and neurogenesis within weeks, however 4th week post MCAO shows prominent recovery. We summarized that rat’s brain shows spontanenous improvement in chronic phase of stroke ischemia and angiogenesis and neurogenesis still happends until week 12th.

Endoscopic Third Ventriculostomy for an Idiopathic Disproportionately Large Communicating Fourth Ventricle: A Case Report

A disproportionately large communicating fourth ventricle (DLCFV) is a rare condition. A 34-year-old man experienced severe headaches, nausea, vomiting, and gait disturbance. Initial brain computed tomography (CT) showed markedly dilated ventricles with prepontine cistern shrinkage. Following extraventricular drain (EVD) insertion, approximately 400 mL/d of cerebrospinal fluid (CSF) was removed over 8 days. During this time, no significant changes in ventricle size were observed on CT images or the facial pain scale (FPS). We then performed an endoscopic third ventriculostomy and changed the drainage catheter. Immediately after surgery, the patient’s symptoms were relieved, and the drainage volume gradually decreased. EVD was successfully removed on the eighth postoperative day. Our experiences suggest that neurosurgeons should consider the importance of a third ventriculostomy for the diagnosis and treatment of DLCFV.

Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention

OBJECTIVE Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. METHODS Twenty-five very preterm neonates (born at ≤ 32 weeks’ gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. RESULTS The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson’s r = −0.403, p = 0.046) and improved cognitive (r = −0.554, p = 0.047), motor (r = −0.487, p = 0.048), and language (r = −0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = −0.483, p = 0.014) and improved cognitive (r = −0.711, p = 0.001), motor (r = −0.675, p = 0.003), and language (r = −0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). CONCLUSIONS In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.

A Heterozygous Mutation in Cardiac Troponin T Promotes Ca2+ Dysregulation and Adult Cardiomyopathy in Zebrafish

Cardiomyopathies are a group of heterogeneous diseases that affect the muscles of the heart, leading to early morbidity and mortality in young and adults. Genetic forms of cardiomyopathy are caused predominantly by mutations in structural components of the cardiomyocyte sarcomeres, the contractile units of the heart, which includes cardiac Troponin T (TnT). Here, we generated mutations with CRISPR/Cas9 technology in the zebrafish tnnt2a gene, encoding cardiac TnT, at a mutational “hotspot” site to establish a zebrafish model for genetic cardiomyopathies. We found that a heterozygous tnnt2a mutation deleting Arginine at position 94 and Lysine at position 95 of TnT causes progressive cardiac structural changes resulting in heart failure. The cardiac remodeling is presented by an enlarged atrium, decreased ventricle size, increased myocardial stress as well as increased fibrosis. As early as five days post fertilization, larvae carrying the TnT RK94del mutation display diastolic dysfunction and impaired calcium dynamics related to increased Ca2+ sensitivity. In conclusion, adult zebrafish with a heterozygous TnT-RK94del mutation develop cardiomyopathy as seen in patients with TnT mutations and therefore represent a promising model to study disease mechanisms and to screen for putative therapeutic compounds.

Chloroquine Decreases Cardiomyocyte Autophagy and Improves Cardiac Function in a Mouse Model of Duchenne Muscular Dystrophy

Background: Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes. Methods: In the present study, we demonstrated that autophagy was enhanced in the cardiomyocytes of mdx mice, a model of DMD, and that increased autophagy contributed to the development of cardiomyopathy in this context. Results: As assessed by GFP-mRFP-LC3 transfection, autophagosomes were more abundant in cardiomyocytes of mdx mice compared with control wild-type (WT) mice. The number of autophagosomes was significantly enhanced by isoproterenol-induced cardiac stress (4 weeks) in cardiomyocytes of mdx but not WT mice. Simultaneously, isoproterenol increased cardiomyocyte fibrosis in mdx but not WT mice. Administration of chloroquine, an autophagy inhibitor, significantly decreased cardiomyocyte autophagy and fibrosis in mdx mice, even after isoproterenol treatment. Left ventricle size and function were evaluated by echocardiography. Left ventricular contraction was decreased in mdx mice after isoproterenol treatment compared with control mice, which was alleviated by chloroquine administration.Conclusions: These findings suggested that heart failure of DMD could be associated with autophagy. Therefore, autophagy inhibitors, such as chloroquine, are a potential therapeutic modality for heart failure in DMD patients.