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Cardiovascular and metabolic alterations in mice lacking beta1- and beta2-adrenergic receptors.

Targeted disruption of murine beta-adrenergic receptor (beta-AR) genes has helped to clarify the role of specific beta-AR subtypes in regulating cardiovascular development and function. In the mouse, the beta1-AR is primarily responsible for sympathetic regulation of both cardiac chronotropy and inotropy. In contrast, all three beta-ARs play a role in regulating peripheral vascular tone. The impact of ablation of both beta1- and beta2-ARs on cardiac development and on resting cardiovascular and metabolic parameters is remarkably minimal. However, exercise stress reveals additional important contributions of beta1- and beta2-ARs to cardiovascular performance.

Animals↗

Dietary fats and oils in cardiac arrhythmia in rats.

The effect of long-term feeding of various dietary fats and oils on cardiac arrhythmia was studied in an animal model of sudden cardiac death. After confirmation that a dietary supplement of saturated animal fat (SF) increased the animals' susceptibility to develop cardiac arrhythmia under ischemic stress whereas the polyunsaturated fatty acids of sunflower seed oil (SSO) reduced this susceptibility, we found that diets supplemented with either chemically refined palm oil (PO-I) or physically refined palm oil (PO-II) gave results that were generally intermediate in value between the SF and the SSO groups. However, during reperfusion of a previously ischemic heart, both PO-I- and PO-II-supplemented diets appeared to be as effective as SSO in reducing ventricular premature beats. In addition, the incidence of animals displaying severe ventricular fibrillation was much less after palm-oil feeding than it was after SF feeding. These preliminary results warrant further investigation of the potential antiarrhythmic effects of commercial palm oil.

Animals↗

Cardiac atrial natriuretic peptide concentrations in experimental obese mice.

Obesity is usually associated with expansion of blood volume. Therefore, we studied whether obesity affects cardiac and plasma atrial natriuretic peptide (ANP) levels in experimental animal model. Mice made obese with gold thioglucose developed cardiac hypertrophy associated with increases in ANP in atrial tissue and plasma. There were significant (p less than 0.01) correlations between the cardiac ANP concentration and body weight or cardiac weight. These data suggest that enhanced synthesis of atrial ANP in obese mice can be mainly ascribed to increased blood volume associated with cardiac hypertrophy.

Animals↗

Sinus node dysfunction associated with lithium therapy in a child.

Lithium salts have been used extensively in both adults and children during the last 30 years, for the treatment of a variety of psychiatric conditions, including bipolar disorder The cardiac side effects of lithium in adult patients have been well described. However, to the best of our knowledge, there are no reports of lithium-induced cardiac side effects in pediatric patients. We describe the case of a 9-year-old boy who developed cardiac toxicity while receiving long-term lithium therapy.

Child↗

[Cardiac rhabdomyoma surgically treated with success. Review of literature].

The primary cardiac tumors are inusual, the incidence varies in all the ages between 0.005 to 0.05%. In pediatrics patients the incidence is 0.27%. The more frequent tumors during the childhood are the cardiac rhabdomyomas. These tumors are considered benigns. The clinical expression is wide, in the most the cases, the patients are asymptomatic and are detected by murmurs. In the prenatal age are manifested by arrhythmias or hydrops fetalis. The neonates and children may be show cardiac arrhythmias, low cardiac index and sudden cardiac death. The association with tuberous sclerosis had been reported in 81%. We present a neonate with cardiac rhabdomyoma diagnosed in the newborn period when he was asymptomatic, however in the follow-up he developed cardiac failure by obstruction in the out flow tract of the right ventricle. He underwent open cardiac surgery to resect the obstruction. Five months after surgery, the patient remain asymptomatic.

Heart Neoplasms↗

Secundum atrial septal defect repair: long-term surgical outcome and the problem of late mitral regurgitation.

This study examines the clinical and surgical outcome of a group of 55 patients (mean age 33 years) with secundum atrial septal defect who underwent surgical repair of this defect between 1981 and 1990. A group of 25 of these patients underwent late echocardiographic follow-up. Fifty-two patients underwent repair by direct suturing and three by patch closure. Surgical mortality was nil. There was one late death of a 58 year old who died from cardiac failure 4 years after surgery. Late postoperative morbidity consisted of two patients; one, age 63 at the time of surgery, required mitral and tricuspid valve replacement 6 years later and one, age 77 at surgery, developed cardiac failure 3 years later. Atrial fibrillation persisted in the six patients who had the rhythm before surgery and developed postoperatively in two patients aged 54 and 58. Two patients aged 49 and 57 developed immediate postoperative sinus node dysfunction requiring permanent pacing. The mean age at surgery of those six patients who suffered cardiac morbidity was 60 years. The patients with preoperative angiographic evidence of mitral valve prolapse were significantly older (P < 0.001) and had higher mean pulmonary artery pressures (P < 0.001) than patients with normal valves. There was no significant relationship between shunt size and mitral valve prolapse. Echocardiographic follow-up showed persistent mitral valve prolapse in all nine patients who developed the condition preoperatively. Five patients developed mitral valve prolapse with mitral regurgitation postoperatively, one of whom needed subsequent mitral and tricuspid valve replacement. These five patient were on average older (mean age 54) but the group was too small to prove significance. The follow-up data illustrate the current low mortality and morbidity associated with surgical closure of atrial septal defects. Late postoperative echocardiography had revealed not only that mitral valve prolapse persists in those patients who developed the condition pre-operatively but that new cases of mitral valve prolapse with mitral regurgitation can occur after atrial septal defect closure.

Adult↗

Changes in distinct species of 1,2-diacylglycerol in cardiac hypertrophy due to energy metabolic disorder.

OBJECTIVE: The juvenile visceral steatosis (JVS) mouse, a genetic model of systemic carnitine deficiency resulting from carnitine transport mutation, develops cardiac hypertrophy. We determined two putative lipid messengers, 1,2-diacylglycerol (DAG) and ceramide, in JVS and carnitine palmitoyltransferase-I (CPT-I) inhibitor etomoxir-treated mice because these lipids function as co-messengers in the myocardium via modification of protein kinase C activity. METHODS: JVS mice were evaluated at 4 and 8 weeks of age. The effect of long-term etomoxir treatment (45 mg/day) (ET) on mice was investigated in control mice from 4 to 8 weeks of age. As a model of inhibited cardiac hypertrophy, carnitine-treated JVS (CT) mice were produced. Myocardial DAG and ceramide levels and their fatty acid composition were measured. RESULTS: The heart/body weight ratio increased by 100% in JVS mice compared with that in controls, while that of CT mice was normalized in comparison with controls at 8 weeks of age. DAG markedly increased in both JVS and ET mice compared with that in controls (1,677+/-84, 1,258+/-49, and 585+/-58 ng/dry wt, respectively; P<0.01 for controls versus JVS or ET mice), whereas it was decreased significantly in CT mice compared with that in JVS mice (1,066+/-54 ng/dry wt, P<0.01). Furthermore, the fatty acid composition of DAG was similar in JVS and ET mice; in particular, 18:1 and 18:2 were significantly elevated in the myocardium (P<0.01 versus controls). On the other hand, that of DAG in CT mice was similar to that of the control group. In contrast, no difference was observed in myocardial ceramide levels among the groups. CONCLUSIONS: Pharmacological intervention with etomoxir mimics changes in the lipid second messenger characteristic of genetic JVS mice. The results suggest that the increases in distinct DAG species might be involved in the pathogenesis of cardiac hypertrophy as a result of disorder of fatty acid transport.

Animals↗

A novel role for cardiac neural crest in heart development.

Ablation of premigratory cardiac neural crest results in defective development of the cardiac outflow tract. The purpose of the present study was to correlate the earliest functional and morphological changes in heart development after cardiac neural crest ablation. Within 24 hours after neural crest ablation, the external morphology of the hearts showed straight outflow limbs, tighter heart loops, and variable dilations. Incorporation of bromodeoxyuridine in myocytes, an indication of proliferation, was doubled after cardiac neural crest ablation. The myocardial calcium transients, which are a measure of excitation-contraction coupling, were depressed by 50% in both the inflow and outflow portions of the looped heart tube. The myocardial transients could be rescued by replacing the cardiac neural crest. The cardiac jelly produced by the myocardium was distributed in an uneven, rather than uniform, pattern. An extreme variability in external morphology could be attributed to the uneven distribution of cardiac jelly. In the absence of cardiac neural crest, the myocardium was characterized by somewhat disorganized myofibrils that may be a result of abnormally elevated proliferation. In contrast, endocardial development appeared normal, as evidenced by normal expression of fibrillin-2 protein (JB3 antigen) and normal formation of cushion mesenchyme and trabeculae. The signs of abnormal myocardial development coincident with normal endocardium suggest that the presence of cardiac neural crest cells is necessary for normal differentiation and function of the myocardium during early heart development. These results indicate a novel role for neural crest cells in myocardial maturation.

Animals↗

Prospective development of a cardiac surgical registry.

Interest has recently been expressed in developing an Australian adult cardiac surgical registry. Complete national registries of adult cardiac surgery have already been established in many European countries, the USA, Canada and elsewhere. Participating centres contributing to a national registry benefit by being able to benchmark themselves against norms for their particular country. A risk-adjusted database can help surgeons advise their patients of the chances of a good operative outcome. For a surgeon or a surgical unit, the only way to obtain a relevant risk model is to use their own data, and data from units in their particular country. It is also useful to have comparative data from other national registries to compare one's own country with international benchmarks. Since 1996, the European Cardiac Surgical Registry (ECSUR) has put considerable effort into producing unified datasets, harmonised with each other for worldwide use. In 1997, ECSUR launched a minimum cardiac surgical dataset. The worldwide launch of the full international adult cardiac surgical dataset is scheduled for July/August 2000. This dataset would be highly useful for application in Australia. The ECSUR organisation has the capability to analyse data from other countries and could perform this for Australia if requested. However, a better approach would be a national centre in Australia. Funding for national registries around the world has been obtained from Ministries of Health, participating surgical centres, and surgical software vendors. If an Australian national registry is indeed established it will find a ready-made, highly appropriate international cardiac surgical dataset sponsored by ECSUR and the Society of Thoracic Surgeons waiting for adoption by Australia.

Journal Article↗

Cardiac operations in patients with functioning renal allografts.

The Transplant Service at the University of Minnesota Hospitals has performed over 2,000 kidney transplants. Fourteen of these patients have developed cardiac conditions necessitating surgical intervention at intervals of 9 to 144 months (mean 67 months) following their transplantation. These individuals had a mean age of 42 years, and five (36%) were diabetic. All patients had functioning renal allografts with preoperative serum creatinine levels ranging from 1.0 to 1.8 mg/100 ml (mean 1.4 mg/100 ml). Ten patients underwent aorta-coronary saphenous vein bypass grafting. One patient underwent bypass grafting and concomitant left ventricular aneurysmectomy. Native valvular endocarditis developed in two patients. One had tricuspid valve debridement for fungal endocarditis and the other had aortic valve replacement for bacterial endocarditis. The final patient had calcific aortic stenosis and coronary artery disease necessitating aortic valve replacement and coronary bypass. Two patients (14%) died perioperatively. One was a young woman with juvenile-onset diabetes and preinfarction angina who died suddenly several days after the operation; at autopsy, she was found to have an occluded graft to the right coronary artery and extensive infarction. The other was a 54-year-old woman with calcific aortic stenosis, coronary artery disease, and unstable angina who died perioperatively of uncontrollable arrhythmias. Autopsy suggested that she may have had an unsuspected infarction 1 to 2 days before the operation. The remaining 12 patients had uneventful postoperative courses and returned to Class I functional status from a cardiac standpoint. There has been one late death (7%), 45 months after successful coronary artery bypass grafting, as a result of complications attendant to a perforated gastric ulcer. The remaining 11 patients are alive and well at intervals of 8 to 93 months (mean 31 months) after operation. Postoperative serum creatinine levels at hospital discharge averaged 1.6 mg/100 ml, not significantly changed from preoperative levels. Cardiac operations can be performed safely in patients with functioning renal allografts. Patient survival is acceptable and preservation of renal function has been uniformly successful in surviving patients.

Adult↗

Hyperkalemic cardiac arrest following succinylcholine administration: The use of extracorporeal membrane oxygenation in an emergency situation.

We report an 11-year-old male with undiagnosed myopathy, who developed cardiac arrest secondary to severe rhabdomyolysis and hyperkalemia following succinylcholine administration. The patient required extracorporeal membrane oxygenation support from which he was eventually weaned successfully. He died eleven days after the cardiac arrest as a result of apparent ischemic brain injury.

Brain Ischemia↗

Cardiac manifestations of Weber-Christian disease: report and review of the literature.

A patient with chronic systemic Weber-Christian disease who was treated with hydroxychloroquine developed cardiac dilatation with congestive heart failure. Endomyocardial biopsy demonstrated myocyte degeneration and interstitial fibrosis, but no typical features of chloroquine induced cardiomyopathy. Clinical symptoms of congestive heart failure also were recognized in 7 of the 11 reported autopsy cases of Weber-Christian disease having cardiac involvement. This involvement can affect the pericardium and the myocardium.

Adult↗

[A case of cardiac metastasis from non-Hodgkin's lymphoma demonstrating interesting findings through radionuclide studies].

We have presented a quite rare case of non-Hodgkin's lymphoma developing cardiac metastasis which was demonstrated and confirmed by radionuclide studies and autopsy. A 57-year-old male with SVC syndrome underwent radionuclide angiography using 99mTc-HSA prior to 67Ga-citrate and 201Tl-chloride studies for suspected right atrial metastasis from non-Hodgkin's lymphoma. The radionuclide angiography revealed a filling defect in the right atrium. 67Ga and 201Tl studies showed increased accumulations of both nuclides in the right atrium, in congruence with the region showing a filling defect through the radionuclide angiography. These results suggest that combined radionuclide studies, such as radionuclide angiography, 67Ga and 201Tl studies, might be useful in detecting metastatic tumor in the heart.

Citrates↗

Adult T-cell leukemia/lymphoma revealed by a surgically cured cardiac valve lymphomatous involvement in an Iranian woman: clinical, immunopathological and viromolecular studies.

A 60-year-old woman from the town of Mashhad in northeastern Iran developed cardiac failure due to aortic and mitral regurgitations which needed cardiac valve replacement. Histopathological study of the valves revealed a T-cell non-Hodgkin's lymphoma. Blood examination showed leukemic features with 32% of abnormal white blood cells. Human T-cell leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and the specific env HTLV-I sequences were detected in the DNA extracted from the valves and peripheral blood mononuclear cells (PBMC) using polymerase chain reaction technique. Clonal integration of two HTLV-I copies was found in both the valves and PBMC DNA, thus the diagnosis of adult T-cell leukemia/lymphoma (ATL) was established. In contrast to the acute life-threatening cardiac localization, our case met the diagnostic criteria of chronic ATL, this was confirmed by favorable evolution without chemotherapy during the 24 months after diagnosis. According to our knowledge, this is the first report of an isolated lymphomatous cardiac valve involvement, without other cardiac abnormalities. It seems important to underline that the patient originated from Iran where endemicity of HTLV-I has only recently been discovered.

Aortic Valve↗

Identification and management of fetuses at risk for, or affected by, congenital heart block associated with autoantibodies to SSA (Ro), SSB (La), or an HsEg5-like autoantigen.

The congenital heart block (CHB), diagnosed in structurally normal hearts, is strongly associated with, if not caused by, maternal SSA/SSB antibodies (Abs). It develops between 16 and 24 weeks' gestation, coincidentally with the increased transplacental IgG passage, and a window of unique cardiac vulnerability. Less is known about rare CHB cases in which neither cardiac malformations nor SSA/SSB Abs are detectable. We report on four pregnant women: patient 1 at high CHB risk (owing to Sjögren's syndrome (SS) and recurrent pregnancy losses), and patients 2-4 with already established CHB (aggravated by hydrops in patient 2). Abs were found directed to SSA/SSB (patients 1-3) or to an HsEg5-like autoantigen instead (patient 4). During preventive immunoadsorption (IA) from week 19 throughout (patient 1), or therapeutic IA (plus dexamethasone), commenced at week 25 (patient 2), SSA Ab levels decreased per session by 47+/-7 or 80+/-16%, respectively, and hydropic changes resolved. Patient 1 delivered a healthy boy, while patients 2-4 gave birth to CHB-affected children at need for permanent pacing. The irreversibility of complete CHB may justify (a) early ANA screening in all pregnancies (thereby also considering specificities as anti-HsEg5), and (b) preventive immmunoadsorption in high-risk pregnancies (before/during the critical cardiac development phase). This implies controversy, because factors converting risk to disease (in only approximately 2%) are unknown, and prospective randomized treatment studies are not available, given the rarity of CHB.

Autoantibodies↗

[Combination of nitroglycerin and vascular loading in abdominal aorta surgery].

Haemodynamic investigations were performed in nine patients during aortic surgery for Leriche's syndrome. Most of these patients had ischaemic heart disease without cardiac failure. Fluid loading was carried out before and during aortic clamping. It was controlled according to the optimal wedge pulmonary pressure determined the day before surgery. Only six of the nine patients receive nitroglycerin (NTG : 0.2 micrograms X kg-1 X min-1) throughout the operation. Before clamping, cardiac index was improved in patients treated with NTG. During clamping, the patients not treated with NTG showed a drop in cardiac index, an increase in peripheral resistance and in left cardiac work. After declamping, there were no haemodynamic differences between the two groups. Two patients not treated with NTG developed azotaemia postoperatively; one patient developed cardiac failure requiring a dopamine perfusion during surgery. In this series, the association of optimal volume loading with a peroperative perfusion of 0.2 micrograms X kg-1 X min-1 NTG gave a good haemodynamic stability.

Adult↗

Reptilian echocardiography: insights into ontogeny and phylogeny?

We describe the echocardiographic findings in a large reptile-the carpet python. If ontogeny recapitulates phylogeny, the study of reptilian hearts may provide insights into human cardiac development. In addition, the reptilian heart has unique structural and physiological adaptations that may broaden our perspective on evolutionary cardiac adaptation.

Adaptation, Physiological↗

Distinct roles of HF-1b/Sp4 in ventricular and neural crest cells lineages affect cardiac conduction system development.

The heterogeneous cell types of the cardiac conduction system are responsible for coordinating and maintaining rhythmic contractions of the heart. While it has been shown that the cells of the conduction system are derived from myocytes, additional cell types, including neural crest cells, may play a role in the development and maturation of these specialized cell lineages. Previous work has shown that the expression of the hf-1b gene is required for specification of the cardiac conduction system. Using Cre-Lox technology, we conditionally mutated the hf-1b gene in the ventricular and the neural crest cell lineages. Cx40 immunohistochemistry on HF-1b tissue-restricted knockouts revealed a requirement for HF-1b in the cardiomyogenic lineage. Electrophysiological studies identified a second requirement for HF-1b in the neural crest-derived cells. Absence of HF-1b in the neural crest led to atrial and atrioventricular dysfunction resulting from deficiencies in the neurotrophin receptor trkC. Therefore, in this study, we document that a single transcription factor, HF-1b, acts through two separate cell types to direct distinct functions of the cardiac conduction system.

Animals↗