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PubMed1990

Statistical interim monitoring of the Cardiac Arrhythmia Suppression Trial.

The Cardiac Arrythmia Suppression Trial was stopped much earlier than planned. Statistical considerations played a very important role in the decision. Flexible group sequential testing was developed for the trial by implementing a Lan and DeMets procedure with use of the permutation test. We compute P-values from the joint permutation distribution of the test statistics, so we do not need to estimate the sampling distribution which in general is rather difficult to do without strict assumptions. The method also gives an exact test for small samples and allows us to use more complicated or non-Gaussian statistics. We also utilized stochastic curtailment ideas to evaluate various scenarios that might occur during the course of the trial, which assisted the Data and Safety Monitoring Board in making appropriate decisions.

Anti-Arrhythmia Agents↗
PubMed2003

Environmental exposure to mercury and its toxicopathologic implications for public health.

Mercury is a toxic and hazardous metal that occurs naturally in the earth's crust. Natural phenomena such as erosion and volcanic eruptions, and anthropogenic activities like metal smelting and industrial production and use may lead to substantial contamination of the environment with mercury. Through consumption of mercury in food, the populations of many areas, particularly in the developing world, have been confronted with catastrophic outbreaks of mercury-induced diseases and mortality. Countries such as Japan, Iraq, Ghana, the Seychelles, and the Faroe Islands have faced such epidemics, which have unraveled the insidious and debilitating nature of mercury poisoning. Its creeping neurotoxicity is highly devastating, particularly in the central and peripheral nervous systems of children. Central nervous system defects and erethism as well as arrythmias, cardiomyopathies, and kidney damage have been associated with mercury exposure. Necrotizing bronchitis and pneumonitis arising from inhalation of mercury vapor can result in respiratory failure. Mercury is also considered a potent immunostimulant and -suppressant, depending on exposure dose and individual susceptibility, producing a number of pathologic sequelae including lymphoproliferation, hypergammaglobulinemia, and total systemic hyper- and hyporeactivities. In this review we discuss the sources of mercury and the potential for human exposure; its biogeochemical cycling in the environment; its systemic, immunotoxic, genotoxic/carcinogenic, and teratogenic health effects; and the dietary influences on its toxicity; as well as the important considerations in risk assessment and management of mercury poisoning.

Environmental Exposure↗
PubMed1996

Controlling the dynamical behavior of a circle map model of the human heart.

One-dimensional circle maps are good models for describing the nonlinear dynamical behavior of two interacting oscillators. They have been employed to characterize the interaction between a periodic external forcing stimulus and an in vitro preparation of chick embryonic cardiac cells. They have also been used to model some human cardiac arrythmias such as modulated ventricular parasystole. In this paper, we describe several techniques involving engineering feedback control theory applied to a circle map model of human heart parasystole. Through simulations of the mathematical model, we demonstrate that a desired target phase relationship between the normal sinus rhythm and an abnormal ectopic pacemaker can be achieved rapidly with low-level external stimulation applied to the system. Specifically, we elucidate the linear, self-tuning, and nonlinear feedback approaches to control. The nonlinear methods are the fastest and most accurate, yet the most complex and computationally expensive to implement of the three types. The linear approach is the easiest to implement but may not be accurate enough in real applications, and the self-tuning methods are a compromise between the other two. The latter was successful in tracking a variety of period-1, period-2, and period-3 target phase trajectories of the heart model.

Biological Clocks↗
PubMed1989

Pressure support ventilation (PSV) reverses hyperinflation induced isorhythmic A-V dissociation.

We report a case of hyperinflation induced isorythmic atrio-ventricular dissociation with circulatory failure in a patient with chronic obstructive pulmonary disease. The arrythmia was successfully treated by applying "pressure support ventilation" (PSV: 20 cmH2O) which, by decreasing the respiratory rate and increasing the expiratory time reduced the level of auto-PEEP. In order to explain this result the Authors recorded, in the same patient, the level of auto-PEEP and delta FRC obtained with Intermittent Positive Pressure Ventilation (IPPV), Intermittent Mandatory Ventilation (IMV) and PSV at the same gas exchange values. PSV showed a dramatic reduction of both these parameters. (Auto-PEEP: IPPV 12 cmH2O, IMV 17 cmH2O, PSV 7 cmH2O).

Aged↗
PubMed1991

Comparison of the effects of xamoterol, atenolol and propranolol on breathlessness, fatigue and plasma electrolytes during exercise in healthy volunteers.

The influence of clinical doses of drugs that affect beta-adrenoceptors has been examined on heart rate, blood pressure, duration of exercise, and on electrolyte concentrations (Na, K, Ca and Mg) during recovery from exercise in healthy volunteers. The drugs used were a beta 1-adrenoceptor antagonist atenolol, a nonselective beta-adrenoceptor antagonist propranolol, and a cardioselective, partial beta 1-adrenoceptor agonist with 43% ISA activity, xamoterol. The duration of exercise was smaller on propranolol. Maximum exercise heart rate and blood pressure were reduced significantly by propranolol and atenolol. Xamoterol reduced maximum exercise heart rate and had no effect on blood pressure. The degree of breathlessness and fatigue revealed no differences between treatments. Recent evidence has suggested an association between hyperkalaemia and hypomagnesaemia with an increase in the occurrence of arrythmias following acute myocardial infarction. Exercise-induced hyperkalaemia has been suggested as a factor in sudden death. The results confirmed a rise in serum potassium during exercise and attenuation of the fall during recovery under beta-adrenoceptor blockade. Xamoterol was no different from placebo in these respects. Exercise also produced a rise in magnesium levels and during recovery the level fell below baseline. Both these effects were attenuated by propranolol. Calcium levels were not affected by any of the treatments.

Adrenergic beta-Agonists↗
PubMed1980

Comparison of two different loading doses of digoxin in severe renal impairment.

The correct loading dose of digoxin in patients with advanced renal failure is still a matter of discussion. The effects has been studied of loading doses of digoxin 0.625 mg or 1.25 mg given over 48 h according to randomized crossover design to healthy volunteers and to two different groups of patients with renal impairment and the same mean endogenous creatinine clearance of about 15 ml/min. The subsequent maintenance dose for 4 days was digoxin 0.25 mg in the volunteers and 0.125 mg in both groups of patients. The minimum plasma digoxin concentrations before each dose was measured by radioimmunoassay and the plasma levels in the different groups have been compared. In the healthy volunteers no significant difference was found during the study, despite wide variation in the plasma digoxin concentration. In contrast, in patients with renal failure, the group with the higher loading dose showed significantly higher plasma concentrations 24, 36 and 48 h after drug administration, reaching the highest mean value of 2.2 ng/ml at 48 h. However, after 120 h of maintenance therapy a mean digoxin concentration of 1.3 ng/ml was found in both groups. Thus, despite different loading doses identical plasma concentrations were reached during administration of the same maintenance therapy. The higher plasma digoxin concentration obtained during administration of a higher loading dose might be the cause of arrythmias in individual patients.

Adult↗
PubMed1995

Extradural haematomas: how many deaths can be avoided? Protocol for early detection of haematoma in minor head injuries.

Since 1988 in the referral area of the Neurosurgical Unit of Cesena, Italy, a protocol for prevention of deterioration in minor head injury was adopted. Adult patients admitted to any hospital with a GCS score of 15 and 14 (transient) without neurological deficit are submitted to skull x-ray: if a fracture is present the patient is sent for CT to the nearest regional Center. In children skull x-ray is not routinely performed and the patients are admitted for observation to the nearest regional hospital. To assess the effects of such a protocol on morbidity and mortality of extradural haematoma (EDH), from June 1989 to September 1991 a consecutive series of 95 patients harbouring a significant acute EDH was collected. Mean age was 31 years; in 70% trauma was caused by a road traffic accident. The patients were divided into 3 categories: a) Clinical deterioration: mean GCS at surgery was 7.7; out of 27 patients, 12 had anysocoria and 3 bilaterally fixed pupils; the outcome showed only two deaths, one related to the EDH and the other to cardiac arrythmia. Most of the patients deteriorated either during transport after being recognized as at risk or already in Neurosurgery allowing rapid surgical treatment. b) Impaired consciousness (18 cases) and c) Minor head injury (50 cases) are groups of patients treated without morbidity and mortality. If we compare these results with those of a previous study of our group done in 1980-86, there is a statistically significant difference concerning both mortality and morbidity. Our protocol proved therefore to be adequate in preventing most deaths that occurred following clinical deterioration in an apparently low risk patient.

Adolescent↗
PubMed1978

The management of arrhythmias following an acute myocardial infarction.

Arrhythmias are extremely common early after AMI. An arrhythmia is defined by exclusion, either because the sequence of myocardial depolarisation is other than normal or because certain arbitrary limits are exceeded. It follows that the term "arrhythmia" encompasses a complex heterogenous group. Although arrhythmias are defined in electrical terms they are only important because of their immediate, delayed or potential haemodynamic consequences. These occur because of changes in heart rate, loss of atrial transport function, increased myocardial oxygen consumption, decreased myocardial blood flow or loss os synchronicity of ventricular contraction. The sensible and effective management of arrhythmias following acute myocardial infarction requires an appraisal of the haemodynamic consequences, if any, which follow the initiation of the arrythmia. The indications for treating an arrhythmia must be the immediate, delayed or potential haemodynamic loss rather than the mere presence of a rhythm which falls outside the limits of normal. This distinction is perhaps most clearly seen in the case of atrio-ventricular conduction disturbances.

Arrhythmia, Sinus↗
PubMed1981

The "glucose effect" in acute hepatic porphyrias and in experimental porphyria.

The "glucose effect" was investigated in human acute hepatic porphyrias (acute intermittent porphyria, variegate porphyria, coproporphyria and porphobilinogen synthase defect porphyria) and in avian liver cells. 8 patients (7 women) with acute abdominal-neurological porphyria syndrome and 3 patients (2 women) in the remission phase were treated with high carbohydrate intake (approximately 500 g/24 h), mainly in form of intravenous glucose infusions. The biochemical response with a decrease of metabolites of porphyrin biosynthesis was highly significant, accompanied by clinical improvement in 10 courses of 9 patients. Two patients with delayed detection of the disease under the condition of Landry paralysis died after temporary clinical improvement due to ventricular arrythmias in one case and septicemia in the other. The importance of early diagnosis and therapy, and omission of drugs and alcohol cannot be overemphasized. Complementary studies show the "glucose effect" in drug -mediated induction of porphyrin synthesis in liver cells grown in culture: delta-Aminolevulinic acid synthase and protoporphyrin synthesis are repressed.

Acute Disease↗
PubMed2003

What is new in pediatric cardiology.

Enormous advances in the diagnosis and management of heart disease in pediatric patient have taken place during the last-four decades. In this review the authors will concentrate on the developments within the last five to ten years. It will deal with what may be called medical advances. Recent advances in molecular genetics and defining the familial patterns have led to finding that certain genetic and molecular factors are linked to congenital heart disease and arrythmia, thus providing opportunity for improved genetic counseling and future gene therapy. Medical treatment of congenital heart disease targets not only the augmentation of ventricular contractility (positive inotropy) but also addresses the neuro-humoral derangement associated with it. The ultrasound technology for the evaluation of the heart has come a long way from the early A-mode and M-mode capabilities to color Doppler, 2-dimentional and 3-dimentional capabilities.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

The congenital long QT syndrome.

OBJECTIVE: The long QT syndrome (LQTS) is a disorder of the electrical system of the heart, due to dysfunction of the ion channels and involving the repolarisation process. The inherited form occurs when there is a mutation in one of the genes which encode the making of a channel. Prolongation of the QT interval renders the patient vulnerable to an arrythmia called torsade de pointes, resulting in syncope and sudden death. METHODS: Three children with the congenital long QT syndrome presented to the pediatric department, one of them also having a 2:1 atrio-ventricular block. The parents and siblings of these children were screened for the long QT syndrome with an electrocardiogram. 2D echocardiography was done to rule out structural abnormalities and audiometry for deafness. RESULTS: Four family members were identified on screening to have LQTS. Propranolol was started on all children with LQTS. The child with heart block also received a pacemaker. LQTS must be considered in all patients presenting with syncope especially if associated with deafness and/or a family history of sudden deaths in infancy or childhood. CONCLUSION: The corrected QT interval must be determined in all children with heart block since the two conditions are often associated.

Child↗
PubMed2000

Effects of L-THP on Ca2+ overload of cultured rat cardiomyocytes during hypoxia and reoxygenation.

The effects of L-tetrahydropalmatine (L-THP) on the cultured rat cardiomyocytes during hypoxia and reoxygenation and the mechanism of L-THP treating reperfusion-arrythmias were studied. The concentration of intracellular free calcium ([Ca2+]i) of single cultured ventricular myocyte was determined by using EPC-9 light-electricity measurement system. It was found that L-THP (100 mumol/L) could reduce the [Ca2+]i augmentation in single cultured ventricular myocyte during hypoxia and reoxygenation. Verapamil (10 mumol/L) had the similar effect. It was concluded that L-THP could inhibit the Ca2+ overload of cultured rat cardiomyocytes during hypoxia and reoxygenation.

Animals↗
PubMed1995

Hypertension and tachycardia during adrenal manipulation.

The purpose of this report is to draw attention to haemodynamic changes during intraoperative adrenal gland manipulation. Severe hypertension, ventricular tachycardia and subendocardial ischaemia occurred during the manipulation of adrenal gland in a patient who underwent live related donor nephrectomy. The patient responded well to intravenous lidocaine. Plasma norepinephrine concentration was elevated at the time of event. Further investigations after surgery excluded the possibility of phaeochromocytoma. In two years follow-up patient remains well. Suspicion for the cause of the event remains the excessive release of catecholamines with manipulation of a normal adrenal gland. The presence of halothane might have contributed to the arrythmia.

Adrenal Glands↗
PubMed1998

[Pacemaker therapy in patients with atrial fibrillation].

Pacemaker therapy in patients with atrial fibrillation means the best current pacemaker therapy for patients with bradycardias with the aim to avoid the onset of atrial fibrillation and to establish DDD pacing despite of a history of atrial tachyarrhythmias. The newer application of pacing is the suppression of atrial arrhythmias in patients with medical refractory atrial tachyarrhythmias. Patients with slow ventricular rates and permanent atrial fibrillation should receive a VVI-pacemaker, if the bradycardias causes syncope, dizziness or a decrease of their exercise tolerance. In case of chronotropic incompetence the pacemaker should provide rate responsive pacing. Patients with sick sinus syndrome should receive an atrial (AAI) or dual-chamber (DDD) pacemaker, because patients with these in contrast to VVI-pacemakers develop less often atrial fibrillation and subsequent complications such as atrial thromboembolism. A dual-chamber or VDD-pacemaker--the latter connected to a VDD-single-lead--is indicated in patients with advanced AV-block. Atrial fibrillation occurs in 3 to 6% of the patients with no history of arrythmia and is, if pacemakers have no automatic mode switch, an often reason to program the devices to the VVI-pacing mode. Nowadays, most DDD(R)-pacemakers provide an automatic mode switch: During an atrial tachycardia the pacemaker switches to a VVI/VVIR mode and restores the initial DDD(R)-pacing mode with termination of the arrhythmia. In respect to the newer applications, one approach to prevent atrial tachyarrhythmias is permanent atrial pacing. As lower pacing rates of 80 to 90 ppm are usually needed and many patients hardly tolerate these pacing rates, new algorithms are under clinical investigation. Another approach is the simultaneous depolarization of the right and left atrium. Biatrial pacing is performed with one lead in the high right atrium and another lead in the coronary sinus. Another solution is bifocal atrial pacing with leads placed in the high right atrium and in the coronary sinus ostium. One effect of the new pacing techniques is to shorten interatrial conduction times. Therefore, biatrial pacing has become a therapy to prevent atrial arrhythmias deriving from delayed interatrial conduction times. As atrial reentry circuits seem to be important in atrial fibrillation, multisite atrial pacing is also performed in patients with medical refractory paroxysmal atrial fibrillation. Preliminary results suggest a more effective prevention of atrial fibrillation; nevertheless, these techniques should be still restricted to patients enrolled in clinical studies.

Atrial Fibrillation↗
PubMed1999

Indications and operative techniques for combined aortoesophageal resection.

Combined aortoesophageal resection was performed in 8 patients, including 7 with esophageal carcinoma and 1 with aortoesophageal fistula. Aortic resection procedures included segmental resection with permanent aorto-aortic bypass (1 case), segmental resection with graft interposition (1 case), semicircumferential resection with patch aortoplasty (3 cases), wedge resection with lateral aortorrhaphy (1 case), and resection of adventitia (2 cases). Protective methods during aortic cross-clamping included one aorto-aortic permanent bypass, one subclavian-aortic bypass, and three axillo-femoral bypass. Postoperative complications include mediastinal abscess, paresis, arrythmia, and pneumonia. Five patients with esophageal carcinoma died within 6 postoperative months. In 4 of these 5 nonsurvivors, metastasis to distant organs including the liver, bone and peritoneal cavity were found at the time of death or autopsy. Those early recurrence cases were characterized by skip lesions and extensive lymph node metastasis with extranodal invasion. The clinical benefit of aortoesophageal resection will be attained by careful preoperative evaluation for case selection and a sufficient protective method for aortic cross-clamping.

Aged↗
PubMed2005

[Brugada syndrome, a rare cause of syncope].

BACKGROUND: The Brugada syndrome is an autosomal dominant disorder characterized by life-threatening ventricular tachyarrhythmias due to cardiac conductance disturbance without structural heart disease. Mutations of the SCN5A gene cause either a reduction in cardiac Na(+) channel expression or alterations in channel-gating properties, leading to a reduction in Na(+) current amplitude. CASE REPORT: A 37-year-old patient presented after a syncopal spell preceded by dizziness. 6 years ago he had experienced similar symptoms. At that time, physical and clinical examination did not lead to a convincing diagnosis. The initial ECG showed typical signs of the Brugada syndrome with descending ST elevation in leads V(1) and V(2). The ECG changes could be observed over the next 3 days. Thereafter, ECG changes reversed to normal. Ultrasound examination did not show any signs of structural heart disease. During electrophysiological testing no sustained ventricular tachyarrhythmias were inducible. Molecular genetic analysis in this young patient revealed a mutation in the SCN5A gene. According to the patient's symptoms, an automatic cardioverter defibrillator (ICD) was implanted. CONCLUSION: A history of unexplained syncope in patients with a structurally normal heart should raise the suspicion of malignant arrythmias caused by primary arrythmogenic disorders. The diagnosis of Brugada syndrome can be concluded from typical ECG changes (i. e., incomplete right bundle branch block, ST elevation in leads V(1)-V(3)) accompanied by typical symptoms and a positive family history. To date, there is no effective therapy of the gene defect or its pathophysiological correlate available. Therefore, ICD therapy is recommended in symptomatic patients to prevent sudden cardiac death.

Adult↗
PubMedDate not supplied

Cardiac arrhythmias in the human fetus.

Fetal cardiac arrhythmias have been recognized with increasing frequency during the past several years. Most fetal arrythmias are intermittent extrasystoles, often presenting as irregular pauses of rhythm. These are significant only when they occur with appropriate timing to initiate sustained tachycardia, mediated by anatomic bypass pathways. The most common important fetal arrhythmias are: 1) supraventricular tachycardias, and 2) severe bradyarrhythmias, associated with complete heart block. Symptomatic fetal tachycardias are usually supraventricular in origin, and may be associated with the developmet of hydrops fetalis. These patients may respond to antiarrhythmic drug therapy, administered via maternal ingestion or via direct fetal injection. Such therapy should be offered with careful fetal and maternal monitoring, and must be based on a logical, sequential analysis of the electrical mechanism underlying the arrhythmia, and an appreciation of the pharmacology and pharmacokinetics of the maternal, placental fetal system. Bradycardia from complete heart block may either be associated with complex congential heart malformations involving the atrioventricular junction of the heart, or may present in fetuses with normal cardiac structure, in mothers with autoimmune conditions associated with high titres of anti-SS-A or anti-SS-B antibody, which cross the placenta to cause immune-related inflammatory damage to the fetal atroventricular node. This paper reviews experience with the analysis of fetal caridac rhythm, a detailed discussion of the pathophysiology of arrhythmias and their effect on the fetal circulatory system, and offers a logical framework for the construction of treatment algorithms for fetuses at risk for circulatory compromise from fetal arrhythmias.

Algorithms↗