Moderate Ventricular Dilatation Research Articles

Mathematical model of the dependence between cerebral ventricular size and capillary pressure in laboratory animals

Aim: To adapt a mathematical model describing the interaction between fluid media and brain matter for the purpose of definition of the dependence between brain ventricle size and capillary pressure in laboratory animals of two genotypes, BALB/c and C57BL/6. Material and methods. The study included 4 male mice of each inbred strain C57BL/6 and BALB/c at the age of 12 weeks. The brain and cerebrospinal fluid system images were obtained using an 11.7 T horizontal MR scanner (Bruker, BioSpec 117/16 USR, Germany). An axial section at the level of -0.5 mm from bregma was chosen as the geometry for mathematical modelling. To describe the data obtained, the mathematical model was adapted by selecting a scale factor based on the known values of the cerebrospinal fluid formation rate for humans and mice. Results and discussion. The same qualitative pattern of relationship between capillary pressure and mean ventricular wall displacement was observed for all animals considered. Although the selected genetic strains of BALB/c and C57Bl mice differ significantly in terms of cerebral ventricle size, these differences in animal genotype did not affect the nature of this relationship. Changing the parameters of the fluid media interaction in the area of compression or moderate ventricular dilation almost does not lead to an exit from the physiologically acceptable capillary pressure value. In this case, the size of the ventricles changes significantly. In the area of large ventricular dilation, in contrast, there is little change in ventricular size, and this is accompanied by a dramatic increase in capillary pressure far beyond physiologic limits. Thus, the change in ventricular size is an adaptive process associated with pressure fluctuations caused by changes in intracranial fluid flow. The mere fact that some of the values reach the zone of physiologically unacceptable pressures associated, in fact, with death, provided that there is practically no change in ventricular size indicates that such a situation is rarely realized and is possible in case of violation of intracranial fluid media flows associated with the fact that the increase in ventricular size limits adaptive capabilities. Conclusions. The presented animal model will further increase the understanding of the pattern we have established and allow us to move on to attempts at prediction.

P127 – 2762: Micro duplication in OPHN1: Novel possibilty of X-LID cerebellar hypoplasia syndrome (OPHN1 syndrome)

Oligophrenin-1 (OPHN1) encodes a Rho GTPase-activating protein (RhoGAP) whose loss of function is associated with a rare X-linked intellectual disability (X-LID), with specific features and cerebellar hypoplasia involving the vermis. Mutations in OPHN1, located in Xq12, is the most likely to be found, but deletions were also described. We report 2 male siblings with intellectual disability issued from a family with history of X-LID. Morphology recalled the one in OPHN1 syndrome affected patients, with deep-set eyes, marked infra orbital creases, long face and prominent chin. Brain MRI showed slight vermis hypoplasia and moderate asymmetric ventricular dilatation. Sequencing of OPHN1 was performed but no mutation was found. Array comparative genomic hybridization revealed a micro duplication of 172 Kb, mapped on Xq12, inherited from the mother. The proximal breakpoint due to this micro duplication disrupts OPHN1 and probably disturbs the function of RhoGAP. Functional analysis is ongoing.

Biventricular Badness: Rare Images of Ebstein Anomaly of the Tricuspid Valve in a Patient with Hypoplastic Left Heart Syndrome.

We report a rare case of hypoplastic left heart syndrome coexisting in a patient with Ebstein anomaly of the tricuspid valve, which has previously been described only in pathological studies. A fetal echocardiogram at 27-weeks gestation showed severe aortic stenosis with evolving hypoplastic left heart syndrome, significant endocardial fibroelastosis, a dysplastic tricuspid valve with moderate regurgitation, right atrial and ventricular dilation, and signs of fetal congestive heart failure. Due to inadequate left heart size, the patient was not a candidate for fetal intervention for critical aortic stenosis, and repeat studies showed progression of the lesion through the pregnancy. The infant was delivered at 36-weeks gestation with signs of hydrops, and a postnatal echocardiogram confirmed hypoplastic left heart syndrome as well as severe Ebstein anomaly of the tricuspid valve. The infant did not survive to intervention.

Neuroendoscopic options in the treatment of mesencephalic expanding cysts: Report of four cases and review of the literature

ObjectiveMesencephalic expanding cysts, also called lacunae, are rare intraparenchymal, multilobulated cavities of variable diameter mostly localized in the thalamo-mesencephalic region. In symptomatic cases, usually presenting with hydrocephalus or midbrain syndrome, surgical treatment is required and, considering their position, a minimally invasive approach should be preferred. MethodsFour cases of expanding mesencephalic cysts endoscopically treated in three different Italian centers are described. Other possible causes of intracerebral cyst were excluded in all cases by complete neuroimaging and laboratory screening. All patients presented with signs and symptoms of midbrain compression and a slight to moderate ventricular dilation was present in three cases. ResultsAll patients underwent endoscopic cyst fenestration into the ventricle, associated with endoscopic third-ventriculostomy (ETV) in two cases and with cyst wall biopsy in one case. One patient suffered from transient worsening of her hemiparesis due to intraoperative bleeding. All patients showed clinical improvement and a reduction in cyst size on follow-up magnetic resonance images (MRI). ConclusionNeuroendoscopy appears to be an effective, probably definitive surgical option in the treatment of symptomatic mesencephalic expanding cysts. Associating ETV with cyst fenestration seems to offer more complete treatment. Deep intracystic navigation and cyst wall biopsy should be avoided.

A rare cause of neonatal hydrocephalus

AbstractA term male infant was delivered by normal vaginal delivery following an uneventful pregnancy. He presented at 3 days of age with jaundice, weight loss, and poor feeding. He rapidly deteriorated with hypotonia, seizures, a tense fontanelle, and depressed conscious level. A cranial ultrasound scan showed moderate lateral and third ventricular dilatation, with no visible fourth ventricle. Doppler measurements showed absent diastolic flow, confirming markedly raised intracranial pressure. Cerebrospinal fluid pressure was markedly elevated and coagulation profile showed a specific prolongation of the activated partial thromboplastin time. Factor VIII assay confirmed haemophilia and a computed tomography scan showed a posterior fossa haemorrhage that was effacing the fourth ventricle and causing an acute hydrocephalus. He was managed with cerebrospinal fluid drainage and recombinant factor VIII concentrate. Posterior fossa haemorrhage is an unusual cause of acute high pressure hydrocephalus in the term neonate. Haemophilia should be considered as a cause of unusual intracranial haemorrhage in term neonates.

Cerebral salt wasting syndrome: postoperative complication in tumours of the cerebellopontine angle

Cerebral salt wasting (CSW) is a rare complication in posterior fossa tumour surgery. We present two patients with cerebellopontine angle (CPA) tumours who developed cerebral salt wasting postoperatively. Both patients deteriorated in spite of intensive fluid and salt replacement. On CT scan the patients presented mild to moderate ventricular dilation, which was treated with an external ventricular drainage. After the resolution of hydrocephalus, fluid balance rapidly returned to normal in both patients and the clinical status improved. Identification and treatment of secondary obstructive hydrocephalus may contribute to the management of CSW associated to posterior fossa tumour surgery.

Pediatric outcome of children with the prenatal diagnosis of isolated septal agenesis

Isolated Septal Agenesis (SA) is a rare disease with clinical outcomes (especially neurological outcomes) that are unknown. The purpose of this study was to evaluate the clinical outcome of these children. We conducted a retrospective multicenter study of 17 children with an isolated SA or SA combined with a moderate ventricular dilatation (VD) that was diagnosed antenatally and confirmed by a magnetic resonance imaging (MRI) performed in the antenatal period. Of the 17 children, 14 had normal neurological examinations, 2 had language development delay and visuo-spatial dyspraxia, and 3 of the 17 children had behavioral problems. Eight children had neuropsychological evaluations, and the results were normal in six cases. There were 3 cases of septo-optic dysplasia (SOD) diagnosed postnatally, which highlighted the difficulties in assessing the optic tract and hypothalamic-pituitary region in antenatal imaging. Language delay and behavioral disorders were the main abnormalities at follow-up. The discovery of an isolated SA reveals the difficulties of prenatal diagnosis to correlate the neurological and functional prognosis to morphological findings. The prognosis seemed to be good. It appears necessary to improve the diagnostic performance of fetal brain imaging and to follow-up these children prospectively to assess their long-term cognitive-behavioral outcomes.

Clinical Significance of Cerebrospinal Fluid Tap Test and Magnetic Resonance Imaging/Computed Tomography Findings of Tight High Convexity in Patients With Possible Idiopathic Normal Pressure Hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable syndrome with a classical triad of symptoms. The Japanese iNPH guidelines indicate that the cerebrospinal fluid (CSF) tap test and tight high-convexity on magnetic resonance (MR) imaging are important for the diagnosis. The relationships between the effectiveness of CSF shunt surgery in possible iNPH patients, the tap test result, and the MR imaging/computed tomography (CT) findings of tight high-convexity were evaluated in 88 possible iNPH patients (mean age 75 years) with one or more of the classical triad of symptoms, and mild to moderate ventricular dilation. All patients underwent the tap test in the outpatient clinic, and patients and caregivers assessed the clinical changes during one week. The tap test was positive in 47 patients and negative in 41 patients. Surgery was performed in 19 patients with positive tap test, and was effective in 17 patients. Although the findings were inconsistent in some patients, the result of the tap test was found to be highly correlated with the MR imaging/CT finding of tight high-convexity (p < 0.0001), confirming that both these diagnostic tests are promising predictors of shunt effectiveness.

Anesthesia for urgent sequential ventriculoperitoneal shunt revision and cesarean delivery

Many women with cerebrospinal shunts are now reaching the childbearing age and may face risks from shunt malfunction during pregnancy. We report on a case of a 35-year-old primigravida at 36 weeks of gestation who was admitted to our hospital because of headache and cognitive and visual disturbances. At 13 years of age the patient had had a ventriculoperitoneal shunt for hydrocephalus related to an aqueduct stenosis. A computerized tomography scan of the brain showed moderate ventricular dilatation likely resulting from a malfunctioning shunt. On the second day after admission her level of consciousness and neurologic condition suddenly worsened and a second brain scan showed further enlargement of the ventricular system. After multidisciplinary consultation, it was decided to proceed with urgent sequential shunt revision and cesarean delivery. Anesthetic considerations included the risk of difficult airway, rising intracranial pressure and conflicting demands between neurological and obstetrical procedures (such as deep versus low-dose anesthesia). General anesthesia was provided with an oxygen/air mixture (50/50%), i.v. fentanyl (5 μg/kg total dose) and i.v. propofol infusion (4-6 mg·kg −1h −1). Surgical procedures were carried out without complications and both mother and infant were doing well at a 6-month follow-up. An interdisciplinary approach allowed two urgent sequential operations to be performed with a unique anesthetic regimen and excellent maternal and fetal outcome.

Reducing CSF shunt placement in patients with spinal myelomeningocele.

Object:The incidence of hydrocephalus requiring shunts in children with myelomeningocele (MMC) is reported to be very high. Shunt-related complications are a significant cause of morbidity and mortality in this population. In order to minimize shunt placements, we used very rigid clinical selection criteria and followed them in all patients who had myelomeningocele and enlarged ventricles. The follow-up outcome of this retrospective study is reported.Methods:From 2000 to 2007, 23 patients with myelomeningocele and variable degree of hydrocephalus were treated at our institute with primary surgical closure of their myelomeningoceles without a CSF diversion procedure. Patients with severe hydrocephalus who required immediate shunt insertion, and those with no significant associated hydrocephalus were not included in this study. Data regarding the surgical results and complications, postoperative management, and the outcome at follow-up were obtained from their hospital records.Results:Initially increased size of the ventricular system was found to have decreased or stabilized in 17 (81%) patients postoperatively. However, ventriculomegaly continued to progress further in 4 (19%) out of 21 patients. Of 11 patients who presented with enlarged head, eight (73%) patients showed reduction or stabilization in their head circumference. Three (27%) children continued to have progressive head enlargement in the postoperative period and required shunt placement. Signs of raised intracranial pressure observed in six patients on admission, improved in two (33%) and persisted or worsened in four (67%) patients who eventually improved after the insertion of a shunt. Eight (35%) patients experienced wound-related complications following closure of the MMC, including CSF leak in four, wound infection in three, wound breakdown in three, and pseudomeningocele in two patients. Shunt placement was required in the postoperative period in 13 (56.5%) patients to treat raised intracranial pressure in 11 and CSF leak from the wound in two patients.Conclusions:Our experience suggests that the placement of shunts can be reduced by adopting a policy with strict clinical and radiographic criteria. Shunt insertion should be reserved for only those patients who have severe hydrocephalus with clinical features of elevated intracranial pressure. Mild to moderate ventricular dilatation, persistent ventriculomagaly, and some increase in ventricular size after myelomeningocele repair can be treated successfully without a shunt.

Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

BackgroundWorldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences.MethodsTo better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied.ResultsTwelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus, CD4+ and CD8+ T cells, and activated microglia in perivascular areas and brain parenchyma. Genetically resistant, chronically infected mice had substantially less inflammation.ConclusionIn outbred mice, chronic, adult acquired T. gondii infection causes neurologic and behavioral abnormalities secondary to inflammation and loss of brain parenchyma. Perivascular inflammation is prominent particularly contiguous to the aqueduct of Sylvius and hippocampus. Even resistant mice have perivascular inflammation. This mouse model of chronic T. gondii infection raises questions of whether persistence of this parasite in brain can cause inflammation or neurodegeneration in genetically susceptible hosts.

Toward reducing shunt placement rates in patients with myelomeningocele

The prevalence of shunt-dependent hydrocephalus in patients with myelomeningocele has been reported to be in the region of 85%, and shunt-related complications are a significant cause of morbidity and mortality in these patients. Since 1997 the authors have adopted a stringent policy with respect to shunt placement in patients with myelomeningocele, reserving this treatment for those with symptomatic hydrocephalus, severe ventricular dilation at the time of presentation, and/or unequivocal progressive ventriculomegaly after primary closure. They report their experience. The authors reviewed all cases of myelomeningocele involving patients who presented to their institution over a 10-year period. They excluded cases in which the primary closure was carried out at another institution or in which there was not at least 12 months of clinical and imaging follow-up. Data regarding shunt insertion shunt-related complications, and clinical outcome were obtained from a review of the clinical records and analyzed. Fifty-four cases satisfied the inclusion criteria for this study. Shunt insertion was performed in 28 of these cases (51.9%). Applying more stringent guidelines for shunt placement, permitting moderate ventricular dilation, and accepting some mild increase in ventricular size after myelomeningocele closure has resulted in a reduced rate of shunt placement compared with previous series. The rate is comparable to that reported following in utero closure of myelomeningocele.

Thoracic lipomeningocele associated with diastematomyelia, tethered spinal cord, and hydrocephalus

Accessory human tails are uncommon malformations consisting of meningeal and neural structures and possibly occult spinal dysraphism (pseudotails). The thoracic location of a lipomeningocele constituting a pseudotail is very rare. The authors report the case of a young boy harboring a thoracic dorsal appendage consisting of a lipomeningocele and a dermoid cyst that was complicated by the presence of diastematomyelia, tethered spinal cord, syringomyelia, and mild hydrocephalus. The preoperative moderate ventricular dilation was decompressed by the surgical repair of the spinal malformation and required a specific treatment. The authors discuss the rare association of these clinical entities and conclude that complete spine and brain neuroimaging studies are necessary for the correct surgical planning of this kind of malformation.

Heterogeneous expression of hydrocephalic phenotype in the hyh mice carrying a point mutation in α-SNAP

The hyh mouse carrying a point mutation in the gene encoding for soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein alpha (alpha-SNAP) develops inherited hydrocephalus. The investigation was designed to study: (i) the clinical evolution of hyh mice; (ii) factors other than the alpha-SNAP mutation that may influence the expression of hydrocephalus; (iii) the neuropathological features underlying the different forms of clinical evolution. The study included 3017 mice, 22.4% of which were hydrocephalic. The neuropathological study was performed in 112 mice by use of light and electron microscopy. It was found that maternal- and sex-related factors are involved in the heterogeneous expression of hyh phenotype. The clinical evolution recorded throughout a 4-year period also revealed a heterogeneous expression of the hydrocephalic phenotype. Two subpopulations were distinguished: (i) 70% of mice underwent a rapidly progressive hydrocephalus and died during the first 2 months of life; they presented macrocephaly, extremely large expansion of the ventricles, equilibrium impairment and decreased motor activity. (ii) Mice with slowly progressive hydrocephalus (30%) survived for periods ranging between 2 months and 2 years. They had no or moderate macrocephaly; moderate ventricular dilatation and preserved general motor activity; they all presented spontaneous ventriculostomies communicating the ventricles with the subarachnoid space, indicating that such communications play a key role in the long survival of these mice. The hyh mutant represents an ideal animal model to investigate how do the brain "adapt" to a virtually life-lasting hydrocephalus.

Unusual pattern of calcification in congenital toxoplasmosis: the tram-track sign

A preterm boy was born by vaginal delivery at 35 weeks with a normal Apgar score and was admitted to the nursery for respiratory distress and convulsions. Serology for Toxoplasma-specific IgM antibodies was positive. A lateral skull radiograph (Fig. 1) showed a serpentine, gyriform or convoluted pattern of calcification. A CT of the brain (Fig. 2) revealed extensive bilateral gyral pattern of calcification mimicking a tram-track. There was moderate ventricular dilatation with nodular foci of calcification in the basal ganglia and the periventricular region. A pattern of diffusely scattered foci of calcification in the cerebral parenchyma is typical in congenital toxoplasmosis. Gyriform calcification found in this case is unusual and

Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation, and myocardial remodeling in rats.

The objective of this study was to determine whether elevated circulating levels of endothelin (ET)-1 are capable of mediating left ventricular (LV) mast cell degranulation and thereby induce matrix metalloproteinase (MMP) activation. After the administration of 20 pg/ml ET-1 to blood-perfused isolated rat hearts, LV tissue was analyzed for signs of mast cell degranulation and MMP activation. Relative to control, ET-1 produced extensive mast cell degranulation as well as a significant increase in myocardial water content (78.8 +/- 1.5% vs. 74.2 +/- 2.2%, P <0.01), a marked 107% increase in MMP-2 activity (P <0.05), and a substantial decrease in collagen volume fraction (0.69 +/- 0.09% vs. 0.99 +/- 0.04%, P <0.001). Although the myocardial edema would be expected to increase ventricular stiffness, compliance was not altered, and moderate ventricular dilatation was observed (end-diastolic volume at end-diastolic pressure of 0 mmHg of 330.2 +/- 22.1 vs. 298.9 +/- 17.4 microl in ET-1 treated vs. control, respectively, P=0.07). Additionally, pretreatment with the mast cell stabilizer nedocromil prevented ET-1-induced changes in MMP-2 activity, myocardial water content, collagen volume fraction, and end-diastolic volume. These findings demonstrate that ET-1 is a potent cardiac mast cell secretogogue and further indicate that ET-1-mediated mast cell degranulation is a potential mechanism responsible for myocardial remodeling.

The spectrum of cranial ultrasound and magnetic resonance imaging abnormalities in congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection can lead to severe neurological sequelae and (progressive) sensorineural deafness. Neonatal imaging data is mainly based on cranial ultrasound (US) and computed tomography (CT). The additional value of magnetic resonance imaging (MRI) was assessed in congenital CMV infection. The eleven infants studied had a gestational age between 34 and 41 weeks and a birth weight between 1000 and 2780 grams. All but 2 of the infants presented with microcephaly and jaundice at birth. The diagnosis was confirmed postnatally in all infants by isolation of the virus or a polymerase chain reaction (PCR) from the urine. Cranial US was performed in all, MRI in 6 during the neonatal period and later in infancy in 2. Auditory brainstem evoked responses (ABR) were performed in all survivors. US showed periventricular calcifications and/or lenticulostriate vasculopathy associated with mild to moderate ventricular dilatation in 10 of the 11 children. Periventricular (pseudo) cysts were seen in 6 children, being occipital in 4, temporal in 3 and fronto-parietal in 1. The cerebellum appeared to be small in 4 children. MRI provided additional information in 6 of the 8 children. Polymicrogyria in the perisylvian region was seen in 4 children, hippocampal dysplasia in 3 and cerebellar hypoplasia in 4 children. Abnormal signal intensity in the white matter was seen in 4 infants. ABRs were abnormal in 7 of the 9 children. Four children died in the neonatal period, 4 developed severe neurological sequelae, associated with epilepsy and sensorineural deafness in 3. Three children were still too young to be tested, but 2 of these showed sensorineural deafness. MRI provided important additional information, especially with regard to associated polymicrogyria, hippocampal dysplasia, and cerebellar hypoplasia. Calcifications were better seen using US. A combination of US and neonatal MRI should be recommended instead of a CT which is still recommended in the literature.

Long-term assessment and serial evaluation of cardiorespiratory exercise performance and cardiac function in patients with atrial switch operation for complete transposition

At present, a considerable number of patients survive who underwent an atrial switch operation for correction of complete transposition. Our study aimed to assess their long-term exercise performance and the serial evolution of cardiac function. We studied 22 patients 5 to 17 years after an atrial switch operation, and followed them serially for 3.5 +/- 2 years after the first evaluation. Cardiorespiratory exercise function was assessed by analysis of gas exhange and by determination of the ventilatory anaerobic threshold. Echocardiography was performed on all evaluations. All patients were in Class I of the classification of the New York Heart Association at all assessments. Ventilatory anaerobic threshold, however, was significantly lower than normal. It averaged 77.9% +/- 13.7 of the normal mean value at the initial evaluation, and remained stable when re-evaluated later (76.2 +/- 13.7%). At the initial study, the increase in oxygen uptake during graded exercise was below the 95% confidence limit in 6 of the patients, and was below this level in 10 patients at re-assessment. The subnormal values for oxygen uptake during submaximal exercise were associated with moderate to severe haemodynamic dysfunction. At echocardiography, 15 of 17 patients studied twice had mild to moderate right ventricular dilation and tricuspidregurgiation, which remained virtually the same at reasssesment. A stable sinus rhythm was initially present in 17 patients, and persisted in 15 patients during follow-up. At medium term follow-up, cardiorespiratory exercise performance remains stable in patients after atrial switch repair. Serial exercise testing appears useful, because in individual patients in the present study, a decreasing exercise tolerance correlated with development of haemodynamic sequels.

Pacing-induced ventricular remodeling in the chick embryonic heart.

Chronic ectopic pacing in the adult heart induces myocardial hypotrophy close to the pacing site. We have recently described a similar localized decrease of compact myocardium thickness in the chick embryonic heart after 48 h of intermittent apical ventricular pacing. Here we analyze the cellular mechanisms underlying the response of the embryonic heart to pacing. Because the developing heart had been found to adjust its morphology according to functional demands by undergoing cellular hyperplasia or hypoplasia, we hypothesized that the stimulation should result in hypoplasia of the apical ventricular compartment. Morphologic analysis of hearts submitted to 18 h of effective pacing during 48 h showed a mild to moderate ventricular dilatation, a 28% decrease in the apical compact layer thickness with no changes in other ventricular locations, and atrial wall thickening. These modifications were caused by changes in the number of cell layers, whereas cell size was similar between paced and control hearts. Analysis of proliferative activity after 24 h of pacing showed a decrease of 32% in the rate of cell proliferation limited to the apical compact layer exposed to stimulation. No ultrastructural injury or increased cell death was found. These changes were accompanied by down-regulation of the myocardial growth factor fibroblast growth factor-2 but no differences were found in the expression of platelet-derived growth factor. Thus, chronic intermittent ventricular pacing induces myocardial remodeling in the chick embryonic heart, on the basis of locally regulated rates of cell proliferation.

Correlation between cardiac remodelling, function, and myocardial contractility in rat hearts 5 weeks after myocardial infarction

Early after infarction, ventricular dysfunction occurs as a result of loss of myocardial tissue. Although papillary muscle studies suggest that reduced myocardial contractility contributes to this ventricular dysfunction, in vivo studies indicate that at rest, cardiac output is normal or near normal, suggesting that contractility of the remaining viable myocardium of the ventricular wall is preserved. However, this has never been verified. To explore this further, 100 rats with various-sized myocardial infarctions had ventricular function assessed by Langendorff preparation or by isolated papillary muscle studies 5 weeks after infarction. Morphologic studies were also done. Rats with large infarctions (54%) had marked ventricular dilatation (dilatation index from 0.23 to 0.75, p < 0.01) and papillary muscle dysfunction (total tension from 6.7 to 3.2 g/mm2, p < 0.01) but only moderate left ventricular dysfunction (maximum developed tension from 206 to 151 mmHg (1 mmHg = 133.3 Pa), p < 0.01), a decrease less than one would expect with an infarct size of 54%. The contractility of the remaining viable myocardium of the ventricle was also moderately depressed (peak systolic midwall stress 91 to 60 mmHg, p < 0.01). Rats with moderate infarctions (32%) had less marked but still moderate ventricular dilatation (dilatation index 0.37, p < 0.001) and moderate papillary muscle dysfunction (total tension 4.2 g/mm2, p < 0.01). However, their decrease in ventricular function was only mild (maximum developed pressure 178 mmHg, p < 0.01) and less than one would expect with an infarct size of 32%. The remaining viable myocardium of the ventricular wall appeared to have normal contractility (peak systolic midwall stress = 86 mmHg, ns). We conclude that in this postinfarction model, in large myocardial infarctions, a loss of contractility of the remaining viable myocardium of the ventricular wall occurs as early as 5 weeks after infarction and that papillary muscle studies slightly overestimate the degree of ventricular dysfunction. In moderate infarctions, the remaining viable myocardium of the ventricular wall has preserved contractility while papillary muscle function is depressed. In this relatively early postinfarction phase, ventricular remodelling appears to help maintain left ventricular function in both moderate and large infarctions.