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PubMed1996

The structure of the mouse heart in late fetal stages.

Because of the opportunities for genetic manipulation, the mouse has become the major species for models of human disease. Recently, targeted and insertional mutations have induced many novel models of developmental abnormality, including several of congenital heart defects. Interpretation and use of such models requires a precise understanding of the similarities and differences between mouse and human in terms of cardiac development and structure. To this end, we have characterised the late fetal mouse heart using scanning electron microscopy and serial histological sections. Right atrial anatomy is dominated by the venous valves, which separate the orifices of the caval veins from the musculature of the primary atrium. Their structure and location suggest that the pulmonary vein is unlikely to develop from the venous sinus. The pectinated wall of the appendage serves to distinguish the morphologically right atrium, in that it runs around the atrioventricular junction, from the left atrium in which this vestibular region is smooth-walled. The persistence of the left superior caval vein draining to the right atrium, along with a solitary opening for the pulmonary vein in the left atrium, distinguishes the atrial anatomy of the mouse from that of the human. The flap valve of the oval foramen is extensive and represents the embryonic primary atrial septum. The superior rim of the foramen is an infolding of the atrial roof, as has been described in the human, showing that, contrary to orthodox opinion, there is no extensive formation of a secondary atrial septum. The region of the membranous septum seen in the human heart is a relatively thick structure in the late fetal mouse, and is located exclusively in an atrioventricular position. Unlike the human, there is little distinction between the apical trabeculations of the left and right ventricles of the mouse heart.

Animals↗
PubMed1989

Atrial natriuretic peptide binding sites in the mammalian heart: localization to endomural vessels.

The distribution of binding sites for atrial natriuretic peptide in cardiac ventricles of several mammalian species, including rat and human, was determined by in vitro autoradiography. The results revealed a unique anatomic localization of atrial natriuretic peptide binding sites to endomural vessels (Thebesian vessels), which communicate directly with the ventricular chambers. Digital image analysis indicated that these vascular channels possessed binding site densities comparable to those of the renal glomeruli, a major target site for circulating atrial natriuretic peptide. In contrast, no specific labeling of branches of the coronary arteries and veins was detected. The discrete localization of atrial natriuretic peptide binding sites to this "primitive" cardiac circulatory system allows speculation as to the role of this hormone in the regulation of endocardial circulation during cardiac development, normal ventricular function, and in coronary insufficiency.

Adult↗
PubMedDate not supplied

Structural and biochemical remodelling in catecholamine-induced cardiomyopathy: comparative and ontogenetic aspects.

Excessive release or administration of beta-mimetic catecholamines may induce cardiomegaly, necrotic lesions and accumulation of connective tissue in the heart of adult homoiotherms. It was examined here whether similar changes can also be observed at different stages of evolution of the cardiovascular system, i.e. in poikilotherms and in homoiotherms during embryonic life. Sensitivity of the poikilothermic hearts (carp, frog, turtle) to isoproterenol (IPRO) was significantly lower than in the homoiotherms. Necrotic lesions, if present, were localized in the inner spongious musculature which has no vascular supply but which exhibits higher activities of enzymes connected with aerobic oxidation. Moreover, the IPRO-induced decrease of the phospholipid content was also significantly more expressed in the spongious layer. IPRO treatment did not influence the total weight of the fish heart but the proportion of the outer compact layer was significantly higher. These changes were accompanied by an increase of collagen, higher water content and an increase of isomyosin with a lower ATPase activity. The response of the poikilothermic heart to IPRO-induced overload thus differs significantly from that in the homoiotherms. The administration of IPRO during embryonic life of homoiotherms (chick) induces serious cardiovascular disturbances, including cardiomegaly and cellular oedema. Necroses of myofibrils, characteristic of IPRO-induced lesions of adults, were, however, rather exceptional. IPRO did not elevate the concentration of 85Sr (as a calcium homologue) in the immature myocardium; it seems, therefore, that IPRO-induced changes of the embryonic heart are not necessarily due to an intracellular calcium overload. It may be concluded that the character of catecholamine-induced cardiomyopathy is not uniform and depends strictly on the stage of cardiac development.

Adrenergic beta-Agonists↗
PubMed1995

Molecular remodelling in hypertrophied hearts from polyomavirus large T-antigen transgenic mice.

Polyomavirus large T-antigen transgenic mice develop cardiac hypertrophy characterized by an increase in atrial natriuretic factor and beta-myosin heavy chain isoform expression. The aim of this study was to examine changes in proto-oncogene expression in hypertrophied hearts from the transgenic mice. Expression of early growth response-1 (Egr-1) mRNA was detected in hearts from all 15 transgenic mice, but was not detectable in 13 control mice. Reverse transcriptase-polymerase chain reaction experiments using Egr-1-specific primers confirmed the increase in Egr-1 mRNA in enlarged hearts from the transgenic mice. Expression of c-jun, junD and Ha-ras mRNAs was increased in the transgenic hearts 3, 17 and 2.8-fold respectively. Western blots showed an increase in c-myc, c-jun and ras protein in hypertrophied transgenic hearts. Immunofluorescence analyses confirmed an increase in Egr-1 and c-jun protein in transgenic cardiomyocytes. Proliferating cell nuclear antigen, Ki-ras and HSP 90 mRNAs were decreased 22, 2.7 and 3-fold, respectively in the transgenic hearts. Not altered in most hypertrophied hearts was expression of c-fos, junB, p53, c-neu, c-myc, HSP70, HSP27, TGF-beta or IGF 1 mRNAs. Proto-oncogene and growth factor gene expression in hypertrophy induced by PVLT expression is modulated with some proto-oncogenes increased and others decreased in expression.

Animals↗
PubMed1991

Developmental changes in regulation of embryonic chick heart gap junctions.

Embryonic chick myocyte pairs were isolated from ventricular tissue of 4-day, 14-day, and 18-day heart for the purpose of examining the relationship between macroscopic junctional conductance and transjunctional voltage during cardiac development. The double whole-cell patch-clamp technique was employed to directly measure junctional conductance over a transjunctional voltage range of +/- 100 mV. At all ages, the instantaneous junctional current (or conductance = current/voltage) varied linearly with respect to transjunctional voltage. This initial response was followed by a time- and voltage-dependent decline in junctional current to new steady-state values. For every experiment, the steady-state junctional conductance was normalized to the instantaneous value obtained at each potential and the data was pooled according to developmental age. The mean steady-state junctional conductance-voltage relationship for each age group was fit using a two-state Boltzmann distribution described previously for other voltage-dependent gap junctions. From this model, it was revealed that half-inactivation voltage for the transjunctional voltage-sensitive conductance shifted towards larger potentials by 10 mV, the equivalent gating charge increased by approximately 1 electron, and the minimal voltage-insensitive conductance exactly doubled (increased from 18 to 36%) between 4 and 18 days of development. Decay time constants were similar at all ages examined as rate increased with increasing transjunctional potential. This data provides the first direct experimental evidence for developmental changes in the regulation of intercellular communication within a given tissue. This information is consistent with the hypothesis that developmental expression of multiple gap junction proteins (connexins) may confer different regulatory mechanisms on intercellular communication pathways within a given cell or tissue.

Animals↗
PubMed1988

Primary pulmonary artery sarcoma in two children.

The clinical and pathological features of primary pulmonary artery sarcoma in two children are reported. The first patient presented with right ventricular outflow obstruction and underwent successful surgical resection of his tumor. The second patient developed cardiac arrest following a relatively short period of symptoms of right heart failure and could not be revived. The pathological diagnosis in both patients was hemangiopericytoma. To the best of our knowledge, primary pulmonary artery sarcoma in children has not been previously reported.

Adolescent↗
PubMed1999

Treatment of life-threatening huge atrial myxoma: report of two cases.

We herein report two patients with left atrial myxoma who needed an emergency operation. Case 1 was a 48-year-old woman who was injured in a traffic accident and underwent an operation for a right leg fracture. Just after the operation she developed cardiac and respiratory arrest with complaints of chest pain. She was successfully resuscitated and diagnosed to have a left atrial myxoma by echocardiography. Emergency surgery was performed and a giant left atrial myxoma was thus removed from the atrial septum. Case 2 was a 54-year-old housewife who was transferred to our department under the diagnosis of a left atrial myxoma by echocardiography. She complained of dyspnea and chest discomfort. By angiography, the tumor was seen to be partially incarcerated at the diastolic phase. A huge myxoma was removed from the atrial septum which was secured by a patch closure. Cardiac echocardiography can help rule out left atrial myxoma if it is highly suspected. As early surgical mortality is low and the long-term results are good, we strongly believe that patients with cardiac myxoma should be operated on as early as possible, once a diagnosis is made.

Echocardiography↗
PubMed1975

Central nervous system effects of bupivacaine.

The central nervous system and concurrent cardiovascular effects of bupivacaine infusion were studied in cats. It was possible to block cortical E.E.G. desynchronization resulting from a sensory stimulus with bupivacaine. The earliest subcortical change that occurred was rhythmic activity in the amygdala and later in the hippocampus. Occasionally, this activity appeared simultaneously in both these sites. Diazepam pretreatment raised the seizure threshold of bupivacaine. Diazepam was also effective in terminating established seizure activity resulting from bupivacaine. All animals pretreated with diazepam (Valium) or diazepam solvent developed cardiac dysrhythmias durind bupivacaine infusion. The possible clinical significance of the interaction of bupivacaine and diazepam solvent is considered.

Amygdala↗
PubMed2004

Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice.

Mitogen-activated protein (MAP) kinase cascades play a central role in mediating extracellular stimuli-induced intracellular signaling during cell activation. The fourth and least studied mammalian MAP kinase pathway, big MAP kinase 1 (BMK1), also known as extracellular signal regulated kinase 5 (ERK5), is activated in response to growth factors and stress. Activation of this signaling pathway has been implicated not only in physiological functions such as cell survival, proliferation and differentiation but also in pathological processes such as carcinogenesis, cardiac hypertrophy and atherosclerosis. In recent years a series of gene-targeted mice lacking components within the BMK1 cascade have been generated, which have enabled us to investigate the role of the BMK1 pathway within different tissues. Analyses of these knockout mice have led to major discoveries in the role of BMK1 signaling in angiogenesis and in cardiac development. Moreover, studies using conditional BMK1 knockout mice, which circumvent the early embryonic lethality of BMK1 knockouts, have unveiled the importance of BMK1 in endothelial survival and maintenance of vascular integrity during adulthood. Here we summarize current understanding of the function of BMK1, as well as include new data generated from a series of tissue-specific BMK1 knockout mice in an attempt to dissect the role of the BMK1 pathway in various cell types in animals.

Animals↗
PubMed1999

Successful treatment of severe myocardial failure after postpartum haemorrhage with the use of an intra-aortic balloon pump.

We report a 29-year-old primigravid who developed cardiac failure following postpartum haemorrhage unresponsive to volume resuscitation and therapy with catecholamines and phosphodiesterase-inhibitors. Transoesophageal echocardiography (TEE) demonstrated left atrial and ventricular dilatation and global left ventricular hypokinesis. No elevation of serum MB-isoenzyme fraction was detected and other organ functions remained stable. Although emergency cardiac transplantation was considered in the presented patient, the institution of intra-aortic counterpulsation was decided on as a first treatment option. Intra-aortic balloon counter-pulsation rapidly improved cardiac function and led to weaning from pharmacological cardiac support within a few days. Mechanical circulatory assist devices can be life-saving in postpartum-haemorrhage-associated cardiac failure.

Adult↗
PubMed2001

Isolated noncompaction of ventricular myocardium associated with fatal ventricular fibrillation.

A female infant with isolated noncompaction of ventricular myocardium who developed ventricular tachyarrhythmia is described. Wolff-Parkinson-White syndrome was shown by electrocardiography. At 9 months of age, the patient suddenly developed cardiac arrest. Electrocardiography following resuscitation with DC cardioversion demonstrated sinus rhythm without delta wave. The QT interval was normal. Frequent premature ventricular captures caused ventricular fibrillation. DC cardioversion was necessary to terminate frequent attacks of ventricular fibrillation until the introduction of beta blockers and lidocaine. Two-dimensional echocardiogram confirmed the diagnosis of isolated non-compaction of ventricular myocardium. Three months later, the patient died of ventricular fibrillation during respiratory syncytial viral infection.

Cardiomyopathies↗
PubMedDate not supplied

Left ventricular diastolic filling patterns associated with progressive anthracycline-induced myocardial damage: A prospective study.

The objective of this study was to examine changes in diastolic function associated with progressive myocardial damage and their implications. We used prospective sequential Doppler echocardiographic studies of left ventricular (LV) function. The study included 125 consecutive children (median age 6.3 years) receiving anthracyclines to cumulative doses between 45 and 1150 mg/m2 (median 270 mg/m2). We measured peak early (E) and atrial (A) phase filling velocities, EA ratio, deceleration and isovolumic relaxation times (EDecT and IVRT), heart rate, and fractional shortening (SF). Results were compared serially and with individually paired control data matched for body surface area. Progressive myocardial damage was evidenced by a mean SF decrease of 1 absolute %/100 mg/m2 of anthracycline. Six patients developed cardiac failure. After 1-100 mg/m2 of anthracyclines, the EA ratio decreased (mean 1.54-1.40, p = 0.02) and IVRT became prolonged (54 vs 52 msec in controls, p = 0.03). EA ratio increased again with the next dose, usually normalizing thereafter. Twelve patients ended treatment with an EA ratio <1 (1 cardiac death) and 17 with EA ratio >2 (2 cardiac deaths). Diastolic abnormalities were not strongly predictive of reduced SF. Modest changes in left ventricular diastolic filling patterns occur during anthracycline treatment of childhood malignancies. Although 20% of patients have significant abnormalities of diastolic filling by the end of treatment, considerable individual variability renders the pathophysiological and clinical implications of the early changes uncertain.

Adolescent↗
PubMed2000

[Imaging of orbital metastasis of small-intestine carcinoid by octreotide scintigraphy. A critical evaluation of the methodology].

BACKGROUND: An orbital carcinoid metastasis can be specifically imaged by octreotide scintigraphy. Orbital metastases of carcinoid tumors are rare. In the current literature only 27 cases have been published. CASE REPORT: We report on a 59 year-old woman who presented with diplopia 6 years after resection of a carcinoid tumor of the ileum. She also complained about flush and diarrhea. The diplopia was caused by limited extensibility of the right inferior muscle. Computed tomography with contrast revealed an enhancing tumor in the area of the right inferior rectus muscle, which appeared in the MRT as an isointense structure in the T1-weighted image. On staging, we found a contrast-enhancing nodular hepatic lesion. In octreotide scintigraphy, enhancement of the liver, thoracic and abdominal para-aortic lymph nodes and of the right inferior orbit was found. CONCLUSION: The survival times of patients with orbital metastasis of carcinoid tumors range between 7 months and 11 years. No specific treatment is available. Surgical excision is indicated for a symptomatic solitary metastasis. Octreotide is helpful in two ways: (1) as a radiolabeled tracer to detect extra-abdominal and extrahepatic secondary tumors; (2) as a treatment modality for flush and diarrhea, which is successful in over 60% of patients (life expectancy uninfluenced). Our patient is presently being treated with 200 micrograms of octreotide three times a day subcutaneously. Flush episodes and diarrhea have been reduced, but her ophthalmologic symptoms remain unchanged, and she has recently developed cardiac insufficiency.

Antidiarrheals↗
PubMed2005

Lethal gastric rupture caused by acute gastric ulcer in a 6-year-old girl.

Gastric rupture is extremely rare in childhood beyond the neonatal period. We describe a previously healthy 6-year-old girl with a large laceration along the greater curvature on the posterior wall of the stomach. The patient was admitted to a neighboring hospital because of vertigo with 1-day history of intractable vomiting and epigastric pain. Although abdominal distension was noticed during the physical examination, muscular rigidity was not detected on palpation. Laboratory data showed severe hypotonic dehydration and moderate metabolic acidosis with hyperkalemia. She suddenly developed cardiac arrest within an hour after admission. After resuscitation, surgical consultation was obtained. Abdominal X-ray and ultrasound revealed abdominal free air and massive cloudy ascites. At laparotomy, there was a large laceration on the greater curvature of the stomach. Pathology of the gastric wall showed mucosal necrosis while the musculature remained intact consistent with an acute gastric ulcer. Since clinical condition of gastric rupture deteriorates rapidly, early diagnosis and appropriate treatment is essential for good prognosis. One should consider that ulcer formation might cause gastric rupture in childhood.

Acute Disease↗
PubMed2004

Acute and long-term outcome after coronary artery perforation during percutaneous coronary interventions.

BACKGROUND: Coronary artery perforation is a rare but serious complication of percutaneous coronary interventions (PCI). METHODS: We reviewed our database for cases of overt coronary perforation during PCI procedures. Hospital charts, procedural reports, and coronary angiograms of these patients were reviewed, with particular emphasis on mechanisms of perforation, management of the complication, and clinical outcome. RESULTS: Between 01/1998 and 12/2003, a total of 19 cases (mean age: 66+/-8 years, 13 male) of coronary perforation occurred during 6433 PCI procedures performed within this period (incidence: 0.3%). In 12/19 (63%) cases, perforation occurred during recanalisation procedures of chronic total occlusions of coronary arteries. In all but one patient, non-surgical management was attempted: 2 out of 19 (11%) patients were treated conservatively by reversal of heparin anticoagulation. Prolonged balloon inflation at the perforation site was applied in 10/19 (53%) patients. Six (32%) patients received stents (5 of them received covered stentgrafts), 3 (16%) patients developed cardiac tamponade requiring percardiocentesis, and only 2 (11%) patients underwent bailout surgical repair. There were 2 (11%) deaths early after the procedure. CONCLUSION: Coronary perforation during PCI is a rare complication, but is associated with significant morbidity and mortality. In the majority of patients, non-surgical management is both feasible and associated with a high success-rate.

Aged↗
PubMed2007

Evidence in favor of linkage to human chromosomal regions 18q, 5q and 13q for bicuspid aortic valve and associated cardiovascular malformations.

The aim of this study was to identify regions of the genome that harbor genes influencing inheritance of bicuspid aortic valve (BAV) and/or associated cardiovascular malformation (CVM). Aortic valve disease is an important clinical problem, which often results in valve replacement, the second most common cardiac surgery in the United States. In every age group, a majority of cases of valve disease involves a BAV. BAV is the most common CVM with a reported prevalence of 1-2%. Heritability studies indicate that BAV determination is almost entirely genetic. We used a family-based genome-wide linkage analysis with microsatellite markers. Parametric and nonparametric analyses were performed with the software GENEHUNTER and SOLAR (Sequential Oligogenic Linkage Analysis Routines). Thirty-eight families (353 subjects) with BAV and/or associated CVM were assessed. Each participant underwent a standardized echocardiographic examination. The highest LOD score, 3.8, occurred on chromosome 18q between markers D18S68 and D18S1161. Two other chromosomal regions, 5q15-21 (between D5S644 and D5S2027) and 13q33-qter (between D13S1265 and 13qter), exhibited suggestive evidence of linkage (LOD > 2.0). Further, two previously reported linkage peaks on 9q34 and 17q24 were replicated in family specific analyses. No significant X chromosome linkage peaks were identified. In this genome-wide scan we demonstrate for the first time, that BAV and/or associated CVM exhibit linkage to chromosomes 18q, 5q and 13q. These regions likely contain genes whose mutation results in BAV and/or associated CVM indicating their important role in valvulogenesis and cardiac development.

Aortic Valve↗
PubMed2002

Outcome and cost implications of cardiopulmonary resuscitation in the medical intensive care unit of a comprehensive cancer center.

Intensive care unit (ICU) resources are frequently utilized in the supportive care of hospitalized patients with cancer. Patients with cancer reportedly have poor outcomes from cardiopulmonary resuscitation (CPR). The goal of this study was to evaluate the effectiveness and patient care costs of CPR applied to patients already receiving life support in an ICU. The medical records of patients who developed cardiac arrest and underwent CPR in the ICU of a comprehensive cancer center between 1993 and 2000 were reviewed. ICU charges after the first episode of CPR were analyzed. There were 5,196 admissions to the ICU during this time; 406 (8%) of the patients underwent CPR; 67% had hematologic malignancies or had undergone hematopoietic stem cell transplantation: 256 patients (63%) died at the time of the arrest, and in 150 (37%) spontaneous circulation was restored. There were 104 patients (26%) who survived more than 24 hours but ultimately died during their hospitalization; their mean time to death was 4.3 days (95% confidence interval [CI] 2.9-5.6), and mean ICU charges were $45,877 (95% CI $24,802-$66,952). Seven patients (2%) survived to be discharged. Patients who survived after CPR and were discharged from the hospital were those who had acute ventricular dysrhythmias and were resuscitated promptly. The application of CPR to cancer patients receiving life support is costly and typically does not lead to long-term survival. Cancer patients requiring admission to an ICU should receive full supportive care short of resuscitation. Providing assurances that care will remain appropriate, aggressive, and in accordance with the patient's and family's wishes can optimize compassionate care while avoiding futile life-sustaining interventions.

Adolescent↗
PubMed2005

Three-dimensional reconstruction and morphologic measurements of human embryonic hearts: a new diagnostic and quantitative method applicable to fetuses younger than 13 weeks of gestation.

Improvements in the diagnosis of congenital malformations explain the increasing early termination of pregnancies. Before 13 weeks of gestation, an accurate in vivo anatomic diagnosis cannot currently be made in all fetuses with current imaging instrumentation. Anatomopathologic examinations remain the gold standard to make accurate diagnoses, although they reach limits between 9 and 13 weeks of gestation. We present the first results of a methodology that can be applied routinely, using standard histologic section, thus enabling the reconstruction, visual estimate, and quantitative analysis of 13-week human embryonic cardiac structures. The cardiac blocks were fixed, embedded in paraffin, and entirely sliced by a microtome. One of 10 slices was topographically colored and digitized on an optical microscope. Cardiac volume was recovered by semiautomatic realignment of the sections. Another semiautomatic procedure allowed extracting and labeling of cardiac structures from the volume. Structures were studied with display tools, which disclosed the internal and external cardiac components and enabled determination of size, thickness, and precise positioning of ventricles, atria, and large vessels. This pilot study confirmed that a new 3-dimensional reconstruction and visualization method enables accurate diagnoses, including in embryos younger than 13 weeks. Its implementation at earlier stages of embryogenesis will provide a clearer view of cardiac development.

Adult↗