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PubMedDate not supplied

[Management of congenital cardiopathies: state of the art].

Pediatric cardiology has shown an important development in the last 50 years, the first era was the knowledge of the anatomy of congenital heart defects, then it came the understanding of pathophysiology, the third era is therapeutic and is surgical, the first years with high mortality, but after successful cardiac management in infancy it is less than 10% in complex cardiac defects. Catheterization was useful as a diagnostic tool, nowadays it's used therapeutically, and with good results and in some cases surgery and interventional catheterization are used together in the benefit of patients. All the advances in this field resulted form multidisciplinary progresses, among which one may distinguish the better knowledge of pathology, improvement in pre, trans and post operative assessment and management and progress in operative management. Finally, the understanding of the heart of a child, based in a number of investigative methods to clarify cardiac development, and the molecular biology that will help us to understand the syndromatic associations.

Heart Diseases↗
PubMed1978

Serum digoxin and empiric methods in identification of digitoxicity.

A prospective study of consecutive patients admitted to a medical service was undertaken to evaluate the prevalence of cardiac digitalis toxicity and the relative diagnostic values of serum digoxin versus an empiric method, based on calculations of digoxin dose in relation to kidney function and body weight. Of 711 patients admitted, 109 were treated with digitalis on admission. Sixteen of the patients developed cardiac arrhythmias consistent with digitalis intoxication. Five of these, none with serum digoxin above 1.6 ng/ml, were not toxic. The remaining eleven patients, all with serum digoxin levels above 1.6 ng/ml, were either definitely or possibly toxic. A similar borderline between intoxicated and nonintoxicated patients could not be established on the basis of calculations based on body weight and renal function. In all cases in which suspicion of digitalis intoxication was raised, serum digoxin measurements could discriminate between the toxic and the nontoxic patients.

Aged↗
PubMed1998

Cardiac arrest as a possible sequela of critical airway management and intubation.

Immediate cardiac arrest may occur as a result of the physiological consequences of critical airway management, which may include one or all of the following: (1) sedation and/or paralysis, (2) tracheal intubation, and (3) positive pressure ventilation. Two patients are reported, both with myocarditis, who developed cardiac arrest within minutes of simple intubations. Their arrests were not related to technical difficulties of critical airway management. Any disease process that creates a preload-dependent cardiovascular system also creates a situation wherein critical airway management may cause cardiac decompensation. All medications administered to sedate patients and facilitate intubation, as well as mechanical ventilation itself, can cause a decrease in preload. This may be a significant mechanism through which immediate decompensation occurs. Potential conditions that cause preload-dependent cardiovascular systems, as well as alternate therapeutic considerations, are outlined. In these patients intubations should not be delayed, but should be done with extreme caution in anticipation of possible cardiac arrest.

Adolescent↗
PubMed1993

Pathophysiology and clinical aspects of hypertensive hypertrophy.

Individuals with hypertension and electrocardiographic (ECG) evidence of left ventricular hypertrophy (LVH) have a 10-fold greater risk of developing cardiac failure than hypertensives without ECG evidence of LVH. LVH in hypertension is characterized by myocardial fibrosis and structural changes to the small intramural arteries. Hypertensives with or without LVH have reduced coronary vasodilator reserve due to hypertensive disease of small coronary arteries. Prognosis of arterial hypertension is largely determined by cardiac complications. The aim of treatment of hypertensive heart disease is to reverse myocardial hypertrophy in order to prevent progression to hypertensive heart failure, as well as reversal of the hypertensive disease of small coronary arteries in order to improve coronary reserve. On the development of hypertensive heart failure, administration of digitalis, diuretics and angiotensin converting enzyme (ACE) inhibitors should be initiated. Although regression of LVH can be induced by dihydropyridine calcium channel blockers, ACE inhibitors and sympatholytic substances, clinical evidence of the reversal of hypertensive disease of small coronary arteries has still to be established.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Air embolism death of a pregnant woman secondary to orogenital sex.

Air embolism produced by vaginal insufflation is an unusual but potentially lethal consequence of sexual activity, especially in the pregnant patient. Reported here is the case of a young pregnant woman who presented to the ED in full cardiac arrest, with little history to explain her condition. Despite aggressive resuscitative measures, the patient died, but her infant son was delivered via perimortem cesarean section and survived. A high level of suspicion for air embolism should be maintained for young women who unexpectedly develop cardiac arrest, particularly during sexual activity. Air embolism patients may require vigorous medical resuscitation, hyperbaric oxygen therapy, or surgical intervention to survive. The emergency physician should be familiar with the indications for perimortem cesarean delivery in the third-trimester patient presenting to the ED with cardiac arrest.

Adult↗
PubMed1993

A dominant-negative receptor for type beta transforming growth factors created by deletion of the kinase domain.

To prove the postulated role of type beta transforming growth factors (TGF beta) in cardiac development and other events, specific inhibitors of TGF beta signal transduction are needed. We truncated the type II TGF beta receptor cDNA (delta kT beta RII), to delete the predicted serine/threonine kinase cytoplasmic domain. delta kT beta RII was co-transfected into neonatal cardiac myocytes, together with reporter constructs for two cardiac-restricted genes that are regulated antithetically by TGF beta. delta kT beta RII impaired activation of the skeletal alpha-actin promoter by TGF beta 1, -2, and -3 and, conversely, impaired TGF beta inhibition of alpha-myosin heavy chain transcription. Thus, a kinase-defective T beta RII blocks signaling by all three mammalian TGF beta isoforms, and can disrupt both positive and negative control of transcription by TGF beta.

Animals↗
PubMed1998

Ca2+ regulates the kinetics of tension development in intact cardiac muscle.

The goal of this study was to determine whether Ca2+ plays a role in regulating tension development kinetics in intact cardiac muscle. In cardiac muscle, this fundamental issue of Ca2+ regulation has been controversial. The approach was to induce steady-state tetanic contractions of intact right ventricular trabeculae from rat hearts at varying external Ca2+ concentrations ([Ca2+]) at 22 degreesC. During tetani, cross bridges were mechanically disrupted and the kinetics of tension redevelopment were assessed from the rate constant of exponential tension redevelopment (ktr). There was a relationship between ktr and external [Ca2+] that was similar in form to the relationship between tension and [Ca2+]. Thus a close relationship also existed between ktr and tension (r = 0.88; P < 0. 001); whereas at maximal tetanic tension (saturating cytosolic [Ca2+]), ktr was 16.4 +/- 2.2 s-1 (mean +/- SE, n = 7), at zero tension (low cytosolic [Ca2+]), ktr extrapolated to 20% of maximum (3.3 +/- 0.7 s-1). Qualitatively similar results were obtained using different mechanical protocols to disrupt cross bridges. These data demonstrate that tension redevelopment kinetics in intact cardiac muscle are influenced by the level of Ca2+ activation. These findings contrast with the findings of one previous study of intact cardiac muscle. Activation dependence of tension development kinetics may play an important role in determining the rate and extent of myocardial tension rise during the cardiac cycle in vivo.

Animals↗
PubMed2002

Cardiac septation: a late contribution of the embryonic primary myocardium to heart morphogenesis.

Heart morphogenesis comprises 2 major consecutive steps, viz. chamber formation followed by septation. Septation is the remodeling of the heart from a single-channel peristaltic pump to a dual-channel, synchronously contracting device with 1-way valves. In the human heart, septation occurs between 4 and 7 weeks of development. Cardiac looping and chamber formation bring the contributing structures into position to engage in septation. Cardiomyocytes that participate in chamber formation do not materially contribute to septation. The (re)discovery of the role of extracardiac mesenchymal tissue in atrioventricular septation, the appreciation that the formation of the right atrioventricular connection is more than a mere rightward expansion of the atrioventricular canal, the awareness that myocardium originating from the so-called anterior heart field regresses after its function as outflow-tract sphincter ceases, and the recent finding that the myocardialized proximal portion of the outflow-tract septum becomes the supraventricular crest have all significantly enhanced our understanding of the morphogenetic processes that contribute to septation. The bifurcation of the ventricular conduction system is the landmark that separates the contribution of the atrioventricular cushions and the outflow-tract ridges to septation and that divides the muscular ventricular septum in inlet, trabecular, and outlet portions.

Animals↗
PubMed2002

Csx/Nkx2-5 is required for homeostasis and survival of cardiac myocytes in the adult heart.

Csx/Nkx2-5, which is essential for cardiac development of the embryo, is abundantly expressed in the adult heart. We here examined the role of Csx/Nkx2-5 in the adult heart using two kinds of transgenic mice. Transgenic mice that overexpress a dominant negative mutant of Csx/Nkx2-5 (DN-TG mice) showed degeneration of cardiac myocytes and impairment of cardiac function. Doxorubicin induced more marked cardiac dysfunction in DN-TG mice and less in transgenic mice that overexpress wild type Csx/Nkx2-5 (WT-TG mice) compared with non-transgenic mice. Doxorubicin induced cardiomyocyte apoptosis, and the number of apoptotic cardiomyocytes was high in the order of DN-TG mice, non-transgenic mice, and WT-TG mice. Overexpression of the dominant negative mutant of Csx/Nkx2-5 induced apoptosis in cultured cardiomyocytes, while expression of wild type Csx/Nkx2-5 protected cardiomyocytes from doxorubicin-induced apoptotic death. These results suggest that Csx/Nkx2-5 plays a critical role in maintaining highly differentiated cardiac phenotype and in protecting the heart from stresses including doxorubicin.

Animals↗
PubMed2000

[Endothelins and chronic cardiac insufficiency].

Endothelins (ET) comprise a group of substances which are produced and have regulatory functions in different systems of the organism. The main cardiovascular ET is ET-1 which is so far the most potent vasoconstrictor substance. In the pathophysiology of cardiac insufficiency ET-1 promotes cardiac hypertrophy, is involved in vasoconstriction, delayed relaxation and reduced left ventricular contractility. The ET-1 level correlates with pulmonary vascular hypertension. By vasoconstriction of renal arteries ET leads to volume retention. Big-ET is a very efficient neurohumoral marker in the diagnosis of developed cardiac failure which can lead to more accurate prognostic stratification. ET-1 is probably important for assessment of the diagnosis of cardiac insufficiency only in severe cardiac failure. The favourable effect of ET block in cardiac insufficiency was proved for the non-selective ETA/ETB blocker and selective ETA blocker. The selective ETB blocker has an adverse haemodynamic effect in treatment of heart failure but by suppression of aldosterone it can prevent fluid retention. In the treatment of cardiac failure blockers of endothelin converting enzyme seem perspective as they reduce adversely activated neurohumoral factors.

Endothelins↗
PubMed2006

Ryk: a novel Wnt receptor regulating axon pathfinding.

Members of the Wnt family and their receptors, the Frizzleds, are key regulators of pivotal developmental processes including embryonic patterning, specification of cell fate, and determination of cell polarity. The versatility and complexity of Wnt signaling has been further highlighted by the emergence of a novel family of Wnt receptors, the Ryk family. In mammals and flies, Ryk is a key chemorepulsive axon guidance receptor responsible for the establishment of important axon tracts during nervous system development. Although the function of Ryk is currently best understood with respect to this role, its widespread expression, both in developing tissues and in the adult, suggests that Ryk may regulate many essential biological processes. This hypothesis is supported by the multiple developmental phenotypes apparent in Ryk loss-of-function mice. These mice display a variety of embryonic abnormalities, including disruption of skeletal, craniofacial and cardiac development. Here we review Ryk structure and function focusing on its activity as an axon guidance receptor.

Animals↗
PubMed2003

Cardia bifida, defective heart development and abnormal neural crest migration in embryos lacking hypoxia-inducible factor-1alpha.

OBJECTIVES: Previous studies have revealed the essential role of hypoxia-inducible factor-1alpha (HIF-1alpha), a basic helix-loop-helix transcription factor, in cardiovascular development. We attempted to further characterize the underlying mechanisms resulting in abnormal cardiogenesis and defective angiogenesis in mice deficient for HIF-1alpha (HIF-1alpha(-/-)). METHODS: We analyzed cardiovascular development in HIF-1alpha(-/-) embryos at both the macroscopic and microscopic level. Gene expression was determined by RT-PCR, in situ hybridization and immunohistochemistry. Embryonic survival was studied using whole embryo culture. RESULTS: HIF-1alpha deficiency caused cardia bifida in some embryos, while cardiac looping was disturbed in others. These defects did not result from abnormal cardiomyocyte commitment or differentiation, but may relate to defective ventricle formation caused by reduced expression of myocyte enhancer factor 2C (MEF2C) and eHAND. In addition, remodeling of the aortic outflow tract and cephalic blood vessels was abnormal in HIF-1alpha(-/-) embryos. These malformations, together with the hypoplastic pharyngeal arches, are presumably induced by defective neural crest cell (NCC) migration. Impaired migration might be related to insufficient levels of semaphorin-3A (Sema3A). Hyperoxia prolonged survival but only partially rescued the developmental program of cultured HIF-1alpha(-/-) embryos. CONCLUSION: HIF-1alpha is essential for proper cardiac development by modulating both neural crest migration and ventricle formation.

Abnormalities, Multiple↗
PubMed2005

Neuregulin-1alpha and beta isoform expression in cardiac microvascular endothelial cells and function in cardiac myocytes in vitro.

Neuregulins (NRGs) are a family of alternatively spliced growth factors that act through receptor tyrosine kinases of the epidermal growth factor (EGF) receptor family in diverse tissues. The NRG-erbB signaling axis is a critical mediator of cardiac development, and growing evidence supports a role for this system in the intricate cross-talk between the microvascular endothelium and myocytes in the adult heart. The purpose of this study was first to examine the expression of splice variants of the NRG1 gene in adult rat cardiac microvascular endothelial cells and second to compare the function of these variants in cardiac myocytes. We demonstrate that cardiac microvascular endothelial cells in rat culture express multiple Type I NRG1 gene products, including both alpha and beta variants. Comparison of the activity of recombinant NRG1alpha and NRG1beta EGF-like domain proteins in cardiac myocytes shows that the beta ligand is a more potent activator of receptor phosphorylation and intracellular signaling than the alpha ligand, and only the beta ligand stimulated glucose uptake and protein synthesis in these culture conditions. Thus, cardiac microvascular endothelial cells express multiple NRG1 isotypes, but only beta-variants are biologically active on cardiac myocytes.

Alternative Splicing↗
PubMed2001

Growth hormone and the heart.

Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF-I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood-onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF-I levels in acromegaly or after GH replacement therapy in GHD patients. Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans.

Acromegaly↗
PubMed1996

Thrombin activity and early outcome in unstable angina pectoris.

BACKGROUND: The blood coagulation system is frequently activated in the acute phase of unstable angina, but it is unknown whether the augmented function of the hemostatic mechanism may serve as a marker of increased risk for an early unfavorable outcome. METHODS AND RESULTS: Plasma concentrations and 24-hour urinary excretion of fibrinopeptide A were prospectively determined in 150 patients with unstable angina. All patients underwent 24-hour Holter monitoring, during which time urine was collected; at the end of this period, a blood sample was taken and coronary arteriography was performed. The patients were followed up for the occurrence of cardiac events (death and myocardial infarction) until they underwent coronary revascularization or until they were discharged from the hospital. Fibrinopeptide A plasma levels and 24-hour urinary excretion were found to be abnormally elevated in 50% and 45% of the study population, respectively. During hospitalization, 11 patients developed myocardial infarction and 2 patients died. Kaplan-Meier analysis demonstrated a significantly higher probability of developing cardiac events in patients with abnormal rather than normal plasma levels of fibrinopeptide A (P<.01), whereas no difference in outcome was observed between patients with normal and those with abnormal 24-hour urinary excretion. Cox regression analysis showed that the only variables independently related to an early unfavorable outcome were the presence of persistent ischemia during 24-hour Holter monitoring (P<.0001), the presence of intracoronary thrombosis at angiography (P=.016), and abnormal fibrinopeptide A plasma levels (P=.038). CONCLUSIONS: Patients with unstable angina pectoris and abnormal fibrinopeptide A plasma levels are at increased risk for an early unfavorable outcome.

Aged↗
PubMed2002

Experimental studies on the spatiotemporal expression of WT1 and RALDH2 in the embryonic avian heart: a model for the regulation of myocardial and valvuloseptal development by epicardially derived cells (EPDCs).

Epicardially derived cells (EPDCs) delaminate from the primitive epicardium through an epithelial-to-mesenchymal transformation (EMT). After this transformation, a subpopulation of cells progressively invades myocardial and valvuloseptal tissues. The first aim of the study was to determine the tissue-specific distribution of two molecules that are thought to play a crucial function in the interaction between EPDCs and other cardiac tissues, namely the Wilms' Tumor transcription factor (WT1) and retinaldehyde-dehydrogenase2 (RALDH2). This study was performed in normal avian and in quail-to-chick chimeric embryos. It was found that EPDCs that maintain the expression of WT1 and RALDH2 initially populate the subepicardial space and subsequently invade the ventricular myocardium. As EPDCs differentiate into the smooth muscle and endothelial cell lineage of the coronary vessels, the expression of WT1 and RALDH2 becomes downregulated. This process is accompanied by the upregulation of lineage-specific markers. We also observed EPDCs that continued to express WT1 (but very little RALDH2) which did not contribute to the formation of the coronary system. A subset of these cells eventually migrates into the atrioventricular (AV) cushions, at which point they no longer express WT1. The WT1/RALDH2-negative EPDCs in the AV cushions do, however, express the smooth muscle cell marker caldesmon. The second aim of this study was to determine the impact of abnormal epicardial growth on cardiac development. Experimental delay of epicardial growth distorted normal epicardial development, reduced the number of invasive WT1/RALDH2-positive EPDCs, and provoked anomalies in the coronary vessels, the ventricular myocardium, and the AV cushions. We suggest that the proper development of ventricular myocardium is dependent on the invasion of undifferentiated, WT1-positive, retinoic acid-synthesizing EPDCs. Furthermore, we propose that an interaction between EPDCs and endocardial (derived) cells is imperative for correct development of the AV cushions.

Aldehyde Oxidoreductases↗
PubMed2002

Dual effects of the homeobox transcription factor Csx/Nkx2-5 on cardiomyocytes.

A homeobox-containing transcription factor Csx/Nkx2-5 is an important regulator of cardiac development. Many different human CSX/NKX2-5 mutations have been reported to cause congenital heart disease. We here examined the effects of three representative CSX/NKX2-5 mutations on cardiomyocyte differentiation and death with the use of the P19CL6 cardiomyogenic cell lines. Stable overexpression of wild-type CSX/NKX2-5 enhanced expression of cardiac-specific genes such as MEF2C and MLC2v, the promoter activity of the atrial natriuretic peptide gene, and the terminal differentiation of P19CL6 into cardiomyocytes, while all CSX/NKX2-5 mutants attenuated them by different degrees. When exposed to H(2)O(2) or cultured without change of the medium, many differentiated P19CL6 cells overexpressing the mutants, especially the mutant which lacks the carboxyl terminal region just after the homeodomain, were dead, while most of the cells overexpressing wild-type CSX/NKX2-5 survived. Overexpression of the carboxyl terminus-deleted mutant down-regulated expression of an anti-apoptotic protein Bcl-x(L) and up-regulated that of a pro-apoptotic protein CAS, while in the cells overexpressing wild-type CSX/NKX2-5, expression of a pro-apoptotic protein RIP was reduced. Furthermore, overexpression of wild-type CSX/NKX2-5 decreased the number of H(2)O(2)-induced TUNEL-positive cultured cardiomyocytes of neonatal rats, whereas overexpression of the mutants enhanced it. These results suggest that Csx/Nkx2-5 not only regulates expression of cardiac-specific genes but protects cardiomyocytes from stresses and that cell death may be another cause for the cardiac defects induced by human CSX/NKX2-5 mutations.

Animals↗
PubMed1997

Early cardiac failure in a child with Becker muscular dystrophy is due to an abnormally low amount of dystrophin transcript lacking exon 13.

Two Japanese brothers with Becker muscular dystrophy were shown by polymerase chain reaction (PCR) and cDNA sequence analysis to produce a dystrophin gene transcript lacking a single exon: that is, number 13. Despite having the same deletion mutation, the brothers showed clearly different clinical phenotypes: the younger brother developed cardiac failure at the age of nine, while the elder brother was asymptomatic. As alternative splicing was not responsible for this clinical difference, the amount of dystrophin transcript was examined by using reverse transcription semi-nested and parallel PCR. The results showed that the amount of the dystrophin transcript in the younger brother was 20% of that of the elder brother. This finding suggested that lesser amount of dystrophin transcript in the younger brother was responsible for the early onset of cardiac failure. This would represent a novel molecular mechanism for dystrophinopathy.

Cardiac Output, Low↗