Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"Autoresuscitation" (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.
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PMID:Failure of autoresuscitation in weanling mice: significance of cardiac glycogen and heart rate regulation. 1040 76

The inherited long QT syndrome (LQTS) is a familial disease characterized by QT interval changes that often are labile, syncope, and sudden death due to arrhythmias, predominantly in young people. Multiple mutations in five genes encoding structural subunits of cardiac ion channels now have been identified in families with LQTS. Correlations are being described between genotype and specific clinical features in LQTS. However, increasing screening of affected families and sporadic cases has identified incomplete penetrance with highly variable clinical manifestations, even among individuals carrying the same mutations. The identification of LQTS disease genes represents a crucial first step in developing an understanding of the molecular basis for normal cardiac repolarization. This information will be important not only for identifying new therapies in LQTS, but also in further understanding arrhythmias, and their potential therapies, in situations such as heart failure, cardiac hypertrophy, myocardial infarction, or sudden infant death syndrome, where abnormal repolarization has been linked to sudden death. LQTS thus presents a new paradigm to cardiac electrophysiology, in which new molecular information is being brought to bear both on clinical management of patients and on development of a new framework to study the fundamental causes of arrhythmias and new approaches to therapy.
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PMID:Inherited long QT syndromes: a paradigm for understanding arrhythmogenesis. 1063 97

The blood hemoglobin F (HbF) concentration increases in response to chronic arterial hypoxemia and is abnormally elevated in sudden infant death syndrome (SIDS) post-mortem indicating a need for greater oxygen affinity of hemoglobin (Hb) or diminished oxygen usage by tissues or both. Modifying Hb oxygen affinity in rats revealed that increased, rather than decreased, hemoglobin-oxygen affinity permitted survival at greatly reduced environmental oxygen pressures equivalent to high altitude. Decreased Hb-oxygen affinity resulted in bradycardia 5-10 minutes before death. Cardiorespiratory recordings from infants dying suddenly and unexpectedly at home demonstrated cardiovascular failure with hypotension and bradycardia, rather than a cessation of breathing.A fall in blood pressure and acidosis due to hypoxemia in combination with reduced arterial oxygen saturation leads to circulatory failure, heart failure and death. It is speculated that the final mechanism of SIDS mimics failure to survive at high altitudes and very low environmental oxygen pressures when low arterial oxygen pressures combine with decreased Hb-oxygen affinity lead to severe hypoxemia and death.
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PMID:Sudden infant death syndrome: a preconditioning approach to acute arterial hypoxemia. 1086 52

Apparent life-threatening event (ALTE) is a term used to define an event of unknown cause after an infant is found limp, cyanotic, bradycardic, and/or requires resuscitation. Eight to 15% of children with ALTE die of sudden infant death syndrome. Obstructive sleep apnea, bradycardia, gastroesophageal reflux, and laryngotracheal abnormalities are frequently associated with ALTE. Wide QT dispersion is associated with sudden death in heart failure and increased risk of ventricular fibrillation in acute myocardial infarction. Here, we assess QT dispersion in infants with ALTE and its correlation to clinical and electrocardiographic indices. The study included eighty nine infants (age 2.14 +/- 1.8 months, 46 males and 43 females) referred with ALTE to the pediatric emergency room and 18 controls (age 2.77 +/- 2.2 months) who underwent electrocardiogram assessment of QTmin, QTmax, QT dispersion (QT-D), and as well as QTmin, QTmax, and QT-D corrected for heart rate (QTcmin, QTcmax, QTC-D, respectively). All infants were referred at the usual diagnostic tests-the gastroesophageal reflux test, apnea monitoring, Holter ECG monitoring, electroencephalogram, and Doppler echocardiography. QT-D, QTc-D, and QTc-min were significantly greater in the ALTE group (p < 0.01). Greater QTc-D was found in males compared to females (p < 0.001). QT-D and QTc-D showed little or no correlation with age of infant or positivity of diagnostic tests. QTc has been found by multiple regression analysis to be the independent variable with the greatest impact on QTc-D (beta = -0.68, p < 0.001).
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PMID:QT dispersion in infants with apparent life-threatening events syndrome. 1253 Apr 92

Sudden infant death syndrome is the leading cause of death in infancy, but its pathophysiological mechanism has been elusive. Sudden death in adults is a common phenomenon, but the etiology in many cases remains unknown at autopsy. We hypothesize that maladaptive sympathetic bias is the explanatory mechanism that links many cases of sudden demise among adults and infants as companion syndromes. Normally, sympathetic response occurs as an adaptation to physiologic demands of the body through various autonomic reflex arcs such as chemoreceptors. Sympathetic response can become chronic and maladaptive when the normal sympathetic response fails to correct the precipitating physiologic trigger, leading to chronic activation of autonomic reflex arcs. In conditions such as infant sleep apnea or adult heart failure, a pernicious cycle of sympathetic bias may result. Chronic sympathetic bias increases susceptibility to sudden fatal arrhythmias, QT-related and otherwise, in the setting of an exaggerated adrenergic challenge. Examples of such adrenergic stressors include trauma, hypoxia, hypercapnia, acidosis, sleep arousal, illness, medical procedures, and physical activity, all of which have associations with sudden death. Our hypothesis may not only help explain the survival benefits of drugs such as beta-blockers and devices such as synchronization therapy, but also portend new application of similar therapies for many conditions of sympathetic bias.
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PMID:Sudden death among infants and adults: companion disorders of maladaptive sympathetic bias. 1514 36

Postural medicine studies the effects of gravity on human body functions and the ability to influence various diseases by changing the body's position. Orthostasis requires numerous cardiovascular and neurohumoral adaptations to prevent hypotension and a resulting decrease in cerebral perfusion. Sitting upright or in a semi-sitting position reduces venous return in patients with heart failure, intracranial pressure in patients with intracranial hypertension, intraocular pressure in glaucoma patients and may decrease gastro-oesophageal reflux. A left recumbent posture also decreases reflux. A right lateral position results in a lower sympathetic tone than lying on the left side and is beneficial in patients with heart failure or after an infarction without bradycardia. A 40 to 70% decreased prevalence of the sudden infant death syndrome has been observed since the recommendation to avoid laying infants to sleep in a prone position. Sleeping in a supine posture increases the severity of sleep apnoea compared to a lateral position. In patients with acute respiratory distress syndrome, a prone position can rapidly improve blood oxygenation. Idiopathic oedema, orthostatic proteinuria, intradiscal pressure and venous circulation in legs are improved in the decubitus position, whereas arterial flow is reduced. Health risks due to microgravity and prolonged bed rest, such as osteoporosis, venous thrombosis or pressure sores, are discussed.
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PMID:The role of body position and gravity in the symptoms and treatment of various medical diseases. 1555 Nov 57

The immature and mature heart differ from each other in terms of excitability, action potential properties, contractility, and relaxation. This includes upregulation of repolarizing K(+) currents, an enhanced inward rectifier K(+) (Kir) current, and changes in Ca(2+), Na(+), and Cl(-) currents. At the molecular level, the developmental regulation of ion channels is scantily described. Using a large-scale real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assay, we performed a comprehensive analysis of ion channel transcript expression during perinatal development in the embryonic (embryonic day 17.5), neonatal (postnatal days 1-2), and adult Swiss-Webster mouse hearts. These data are compared with publicly available microarray data sets (Cardiogenomics project). Developmental mRNA expression for several transcripts was consistent with the published literature. For example, transcripts such as Kir2.1, Kir3.1, Nav1.5, Cav1.2, etc. were upregulated after birth, whereas others [e.g., Ca(2+)-activated K(+) (KCa)2.3 and minK] were downregulated. Cl(-) channel transcripts were expressed at higher levels in immature heart, particularly those that are activated by intracellular Ca(2+). Defining alterations in the ion channel transcriptome during perinatal development will lead to a much improved understanding of the electrophysiological alterations occurring in the heart after birth. Our study may have important repercussions in understanding the mechanisms and consequences of electrophysiological alterations in infants and may pave the way for better understanding of clinically relevant events such as congenital abnormalities, cardiomyopathies, heart failure, arrhythmias, cardiac drug therapy, and the sudden infant death syndrome.
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PMID:Large-scale analysis of ion channel gene expression in the mouse heart during perinatal development. 1698 3

The SCN5A-encoded cardiac sodium channel underlies excitability in the heart, and dysfunction of sodium current (I(Na)) can cause fatal ventricular arrhythmia in maladies such as long QT syndrome, Brugada syndrome (BrS), and sudden infant death syndrome (SIDS). The gene GPD1L encodes the glycerol phosphate dehydrogenase 1-like protein with homology to glycerol phosphate dehydrogenase (GPD1), but the function for this enzyme is unknown. Mutations in GPD1L have been associated with BrS and SIDS and decrease I(Na) through an unknown mechanism. Using a heterologous expression system, we show that GPD1L associated with SCN5A and that the BrS- and SIDS-related mutations in GPD1L caused a loss of enzymatic function resulting in glycerol-3-phosphate PKC-dependent phosphorylation of SCN5A at serine 1503 (S1503) through a GPD1L-dependent pathway. The direct phosphorylation of S1503 markedly decreased I(Na). These results show a function for GPD1L in cell physiology and a mechanism linking mutations in GPD1L to sudden cardiac arrest. Because the enzymatic step catalyzed by GPD1L depends upon nicotinamide adenine dinucleotide, this GPD1L pathway links the metabolic state of the cell to I(Na) and excitability and may be important more generally in cardiac ischemia and heart failure.
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PMID:GPD1L links redox state to cardiac excitability by PKC-dependent phosphorylation of the sodium channel SCN5A. 1966 41

The classification of an unexpected infant death as sudden infant death syndrome (SIDS) depends upon a complete autopsy, death scene investigation, and review of medical history to exclude known causes of death. Death from occult neoplastic disease in infancy is extremely rare but is within the broad differential diagnosis of SIDS. We report the sudden and unexpected death of a 1-month-old infant from a hepatic (infantile) hemangioendothelioma. The physiologic mechanism of death was likely cardiac failure induced by the circulatory demands of this large vascular tumor and respiratory compromise from diaphragmatic thoracic incursion. The clinical progression and pathology of these relatively common tumors of infant livers are extremely variable. This case dramatically illustrates the potential for fatal outcome of this tumor, as well as the need for autopsy to determine the cause of sudden and unexpected death in an infant.
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PMID:Hepatic hemangioendothelioma presenting as sudden unexpected death in infancy: a case report. 2046 26

Left ventricular noncompaction/hypertrabeculation is a condition which is characterized by a highly trabeculated, "spongy" myocardium.It can present at any age with heart failure, arrhythmia and/or thromboembolic events.A wide variety of mutations have been found to be a cause of hypertrabeculation and it is possible that there is a continuum of hypertrophic cardiomyopathy, dilated cardiomyopathy and hypertrabeculation/noncompaction.We present a case of left ventricular hypertrabeculation which presented as sudden infant death syndrome and we propose that this entity may be a hidden cause of arrhythmic death in some infants presenting as sudden infant death syndrome.
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PMID:Sudden infant death syndrome and left ventricular hypertrabeculation-hidden arrhythmogenic entity? 2098 Nov 30


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