Serum palmitoleate acts as a lipokine in subjects at high cardiometabolic risk.

BACKGROUND AND AIM: Clinical data on the role as a lipokine of de novo lipogenesis-derived palmitoleic acid (C16:1n-7cis) in serum non-esterified fatty acids (palmitoleate) are scarce. We aimed to assess whether palmitoleate relates to cardiometabolic risk. METHODS AND RESULTS: In this cross-sectional study we included 358 individuals aged 30-65-years at high cardiovascular risk. We tested the association of palmitoleate (determined by gas chromatography) with metabolic syndrome (MS) and its components (defined by ATPIII criteria), fatty liver index (a surrogate of non-alcoholic fatty liver disease [NAFLD]), and subclinical atherosclerosis (determined as ultrasound-measured carotid intima-media thickness and arterial stiffness). Palmitoleate concentration was higher in women compared with men (median ± range interquartile, 1.36 ± 0.96 vs. 0.97 ± 0.77 µmol/L respectively, P < 0.001). In both genders palmitoleate concentration was associated with a higher prevalence of MS: men, odds ratio [OR: 1.12 (95%CI: 1.03; 1.23, P = 0.010)]; women [OR: 1.07 (95%CI: 1.03; 1.13, P = 0.005)], and all of its components except low HDL-cholesterol and hypertriglyceridemia. Palmitoleate was also associated with increased risk of NAFLD in both men [OR: 1.12 (95%CI: 1.03; 1.29, P = 0.031)] and women [OR: 1.11 (95%CI: 1.05; 1.19, P = 0.001)]. No associations with subclinical atherosclerosis were detected. CONCLUSIONS: Our observational data supports a relationship between de novo lipogenesis-derived circulating palmitoleic acid (palmitoleate) and increased cardiometabolic risk.

FABP4 plasma concentrations are determined by acquired metabolic derangements rather than genetic determinants.

BACKGROUND AND AIMS: Circulating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 plasma levels and subclinical arteriosclerosis in patients with obesity, metabolic syndrome (MS) or type 2 diabetes (T2DM). METHODS AND RESULTS: We studied 440 individuals with obesity, MS, T2DM or other cardiovascular risk conditions who attended the vascular medicine and metabolism unit of our hospital. Anamnesis, physical examination and anthropometry data were recorded. Standard biochemical parameters were determined. Plasma FABP4 concentrations were measured. Carotid intima-media thickness (cIMT) was assessed using ultrasonography. The following FABP4 gene single-nucleotide polymorphisms (SNPs) were analyzed: rs3834363, rs16909233, rs1054135, rs77878271, rs10808846 and rs8192688. None of the studied gene allele variants were hyper-represented in patients grouped according the presence of metabolic alterations nor were they associated with the FABP4 concentration. The FABP4 gene variants did not determine cIMT differences between the groups. In a multivariate analysis, gender and BMI, but not gene variants, significantly determined plasma FABP4 concentrations. CONCLUSIONS: In clinical settings, the circulating FABP4 levels are determined by the acquired metabolic derangements and not genetic variation.

APOA5 gene expression in the human intestinal tissue and its response to in vitro exposure to fatty acid and fibrate.

BACKGROUND AND AIMS: APOA5, a key gene regulating triglyceride (TG) levels, is reported to be expressed exclusively in the liver where it may regulate TG-rich particle synthesis and secretion. Since the same lipoprotein processing occurs in the intestine, we have postulated that this organ would also express APOA5. METHODS AND RESULTS: We have detected the APOA5 gene expression in C57BL/6J mouse and in human small intestine samples. In humans, it is expressed mainly in the duodenum and colon, with messenger RNA (mRNA) levels four orders of magnitude lower than in the liver, and the protein product being one-sixth of the liver equivalent. Subsequently, we carried out in vitro experiments in TC-7/CaCo(2) human intestinal cells to analyse the expression of APOA5, APOC3, APOB and MTP genes after the incubation with long- and short-chain fatty acids, and a peroxisome proliferator-activated receptor alpha (PPARα) agonist (Wy 14643, a fibrate therapeutic agent). In the TC-7 cell line, APOA5 expression was significantly upregulated by saturated fatty acids. The short-chain fatty acid butyrate increased APOA5 expression almost fourfold while APOB was downregulated by increasing butyrate concentrations. When TC-7 cells were incubated with PPARα agonist, the APOA5 expression was increased by 60%, while the expression of APOB, MTP and APOC3 was decreased by 50%, 30% and 45%, respectively. CONCLUSION: Our results demonstrate that APOA5 is expressed in the intestine, albeit at a much lower concentration than in the liver. While it remains to be determined whether intestinal apo A-V is functional, our in vitro experiments show that its expression is modifiable by dietary and pharmacological stimuli.

Effects of therapeutic lifestyle changes on peripheral artery tonometry in patients with abdominal obesity.

BACKGROUND AND AIMS: Abdominal obesity (AO) is associated with endothelial function (EF) alteration and increased global cardiovascular (CV) risk. Therapeutic lifestyle changes (TLSC) reduce CV risk, but the impact on EF assessed by peripheral artery tonometry (PAT) is unknown. In this study, we aimed to prospectively assess the effects of TLSC on EF measured by PAT in increased CV risk patients with AO. METHODS AND RESULTS: 150 patients with AO and moderate CV risk were randomized to groups receiving a one-year intervention of either conventional medical care (control group, CG) or an intensive TLSC program (intervention group, IG). Vascular studies (EF by PAT, intima-media thickness (IMT)) and lifestyle (LS) assessment were performed before and after intervention. The PAT ratio improved in the IG and worsened in the CG. The global CV risk was reduced (P = 0.017) in the IG due to a significant decrease in systolic blood pressure (P < 0.001), increase in HDL cholesterol and ApolipoproteinA1 (P = 0.013). More individuals in the IG than in the CG quit smoking (P = 0.001) and increased their physical activity (P = 0.014). The improvement in at least two LS components was associated with a PAT ratio increase (2.44 IC: 95% 0.99-6.00, P = 0.051). The PAT ratio increase determined less IMT progression (-1.1 IC: 95% 0.91-1.00, P = 0.053). CONCLUSIONS: Good adherence to a TLSC program reduces global CV risk and determines PAT ratio improvement. The PAT ratio increase is the main determinant of lower IMT progression.

The APOA5-1131 T>C variant enhances the association between RBP4 and hypertriglyceridemia in diabetes.

BACKGROUND AND AIM: Type 2 diabetic patients have an increased prevalence of hypertriglyceridemia. RBP4 has been associated with insulin resistance and hypertriglyceridemia in obesity, the metabolic syndrome and type 2 diabetes. APOA5 is proposed to be a genetic modulator of triglycerides. The aim of this study was to evaluate the relationship between RBP4 plasma levels and lipid disturbances and to determine the impact of the APOA5-1131 T>C variant on this relationship in type 2 diabetic patients. METHODS AND RESULTS: A total of 165 type 2 diabetic patients were included in the study. RBP4 plasma levels and the APOA5-1131 T>C variant were determined and the complete lipid profile was assessed by sequential ultracentrifugation. RBP4 was positively correlated with triglyceride levels in plasma and with all the components of triglyceride-rich lipoproteins. Despite the fact that a statistically significant relationship between the APOA5 genetic variant and RBP4 plasma levels was not found, the hypertriglyceridemic effect of high RBP4 levels was enhanced by the presence of the APOA5-1131 T>C genetic variant. Correlation coefficients were 2-fold higher for TC carriers compared to TT carriers with regard to RBP4 plasma levels and all the components of triglyceride-rich lipoproteins. Those type 2 diabetic patients with high RBP4 plasma concentrations and who were TC carriers showed an increased incidence of hypertriglyceridemia (OR=7.46, P=0.010). CONCLUSION: RBP4 is associated with hypertriglyceridemia in type 2 diabetic patients. The RBP4 effect is conditioned by the presence of the APOA5-1131 T>C genetic variant.

Extracellular FABP4 uptake by endothelial cells is dependent on cytokeratin 1 expression.

AIMS: The aim of this study is to determine the physical and functional interplay between fatty acid-binding protein 4 (FABP4) and its membrane receptor-like candidate protein, cytokeratin 1 (CK1), and to determine the effect of hindering CK1-mediated FABP4 cellular uptake on non-disturbed or metabolically stressed endothelial cells. METHODS: We monitored the direct interaction between FABP4 and CK1 using surface plasmon resonance, and the effects of blocking exogenous FABP4 (eFABP4) cellular uptake were determined by using specific siRNA to knock down the expression of CK1 in human umbilical vein endothelial cells (HUVECs). The expression and nuclear translocation of transcription factors involved in oxidative stress (NRF2) and inflammation (p65 subunit of NF-ĸB transcription factor) were determined by Western blotting analysis. RESULTS: Our data showed that FABP4 and CK1 bind to each other and that the putative FABP4 binding domain would be within the 151GIQEVTINQSLLQPLNVEID170 CK1 sequence. We determined that in non-disturbed or metabolically stressed endothelial cells, eFABP4 regulates the cellular response to oxidative stress. In addition, we also found that in the presence of palmitate, eFABP4 increases the pro-inflammatory effects induced by palmitate per se, probably due to an increase in the transport of palmitate inside cells, suggesting that these FABP4-mediated pro-oxidative and pro-inflammatory effects are dependent on CK1 expression. CONCLUSIONS: We demonstrated that CK1 facilitates eFABP4 cellular uptake in endothelial cells. Therefore, the CK1-targeted inhibition of exogenous FABP4 cellular uptake might be a potential therapeutic strategy to protect endothelial cells against FABP4-induced activation of inflammation and oxidative stress.

Antioxidative and antiatherosclerotic effects of human apolipoprotein A-IV in apolipoprotein E-deficient mice.

Mice expressing human apolipoprotein A-IV (apoA-IV) mainly in the intestine were obtained in an apolipoprotein E-deficient (apoE(0)) background (apoA-IV/E(0) mice). Quantification of aortic lesions and plasma lipid determination showed that compared with their control apoE(0) counterparts, the apoA-IV/E(0) mice are protected against atherosclerosis without an increase in HDL cholesterol. Because oxidized lipoproteins play an important role in atherogenesis, we tested whether the protection observed in these animals is accompanied by an in vivo reduction of the oxidation parameters. The lag time in the formation of conjugated dienes during copper-mediated oxidation, the aggregation state of LDL, and the presence of anti-oxidized LDL antibodies were measured. The presence of oxidized proteins in tissues and the presence of oxidation-specific epitopes in heart sections of atherosclerotic lesions were also analyzed. Except for lag time, the results showed that the oxidation parameters were reduced in the apoA-IV/E(0) mice compared with the apoE(0) mice. This suggests that human apoA-IV acts in vivo as an antioxidant. In addition, human apoA-IV accumulation was detected in the atherosclerotic lesions of apoA-IV/E(0) mice, suggesting that apoA-IV may inhibit oxidative damage to local tissues, thus decreasing the progression of atherosclerosis.

Physical activity below the minimum international recommendations improves oxidative stress, ADMA levels, resting heart rate and small artery endothelial function.

BACKGROUND: A moderate level of physical activity (PA), such as a daily 30-min walk, reduces cardiovascular risk. There is a lack of evidence about the cardiovascular benefits of PA below this recommendation of minimum PA level. OBJECTIVE: We aimed to study the impact of a lower level of PA on cardiovascular health. DESIGN: Sixty-four overweight/obese men and women were enrolled in a community programme consisting of 4 months of 1h, low-intensity PA two days per week. Before and after the intervention, PA level (METs/h/wk), endogenous antioxidant status (SOD and GPX concentration and activity and oxidised LDL), ADMA concentrations, endothelial function by small artery reactive hyperaemia index (saRHI), and resting heart rate (RHR) were assessed. RESULTS: After the intervention, significant increases in saRHI (P=0.031), SOD and GPX activities, and a decrease in ADMA plasma concentrations, and RHR (P<0.001 for all) were observed. Increases in PA were positively associated with increases in saRHI (r=0.341, P=0.022), GPx (r=0.303, P=0.047) and decreases in RHR (r=-0.302, P=0.047). Multivariate analyses showed that independent predictors of saRHI improvement were an increase in PA (2.65, 95%CI: 1.21-4.01), decrease in RHR (1.91, 95%CI: 1.01-4.98), and an increase in GPx (2.61, 95%CI: 1.16-5.01). CONCLUSION: In obese and overweight men and women, an increase in PA, even below the minimal international recommendations, improves antioxidant capacity, RHR and peripheral small artery reactivity.

Oxidized lipoproteins including HDL and their lipid peroxidation products inhibit TNF-alpha secretion by THP-1 human macrophages.

It has been established that oxidized LDL (ox-LDL) modifies cytokine secretion by macrophages, for example, by reducing tumor necrosis factor alpha (TNF-(alpha) m-RNA. However, little is known about the effects of oxidized high density lipoprotein (ox-HDL). This study reports the effects of ox-HDL subfractions 2 and 3 (ox-HDL2, ox-HDL3) compared with that of ox-LDL and some products of oxidation (hydroperoxides and aldehydes) on the secretion of TNF-alpha from THP-1 human monocytes derived macrophages in vitro. HDL2, HDL3 and LDL were oxidized with 10 microM Cu++ for 12 h and/or 24 h. Native and oxidized HDL and LDL were incubated for 24 h with macrophages with or without LPS (10 ng/ml) after which TNF-alpha secretion was measured in the culture medium. Lipid hydroperoxides and apolar aldehydes were also incubated with the cells for 2 h following which the medium was replaced and TNF-alpha secretion measured after a further 22 h of incubation. An inhibition of TNF-alpha by ox-HDL2 (p < .05), ox-HDL3 (p < .05) and ox-LDL (p < .05) from THP-1 macrophages was observed in the presence and absence of LPS. This inhibition remained the same after incubation with ox-HDL 12 h and 24 h. Hydroperoxides of linoleic acid did not modify TNF-alpha secretion by cells while five out of eight aldehydes analyzed (2,4-heptadienal, hexanal, 2-nonenal, 2-octenal, 2,4-decadienal) inhibited TNF-alpha secretion (p < .05). These findings demonstrate that ox-HDL, and some of its lipid peroxidation products, plays a role in the modulation of the inflammatory response by macrophages as previously observed for ox-LDL.

Oleic acid rich diet protects against the oxidative modification of high density lipoprotein.

Oxidative modifications of lipoproteins could contribute to the development of atherosclerosis, but the influence of dietary fats on high density lipoprotein (HDL) oxidative modification is unknown. This study was designed to determine whether a diet rich in oleic acid could modulate the oxidative modification of HDL3. Twenty two healthy men were randomly placed on a 32-wk crossover study of an oleic acid rich diet supplied by a variant of sunflower oil vs a linoleic acid rich diet provided by conventional sunflower oil. Plasma HDL3 obtained after the diet rich in oleic acid showed a significantly higher oleic acid content in the phospholipid than lipoprotein isolated after the linoleic acid rich diet. HDL3 isolated after the oleic acid rich diet had lower values of thiobarbituric acid reactive substances (TBARS) than HDL3 obtained after the linoleic acid rich diet both for native (mean +/- SE; 0.24 +/- 0.02 vs 0.42 +/- 0.08 nmol MDA/mg protein; p < 0.01) and copper oxidized HDL3 (0.75 +/- 0.06 vs 0.95 +/- 0.07 nmol MDA/mg protein; p < 0.01). Indeed, TBARS for native HDL3 were negatively correlated with the oleic acid to linoleic acid ratio and positively with the percentage of linoleic acid in their phospholipids. Interestingly, HDL3 after both diets had similar antioxidant vitamins A and E content. HDL3 overall composition and fluidity were similar after the two diets. Moreover, HDL3 obtained after both diets produced identical [3H] free cholesterol efflux from human monocyte-derived macrophages (29%) and fibroblasts (26%). In conclusion, HDL3 rich in oleic acid was less easily oxidized regardless of the content of antioxidants such as vitamins A and E. Therefore, dietary monounsaturated fatty acid prevent the oxidative modification of lipoproteins.

2,4-Decadienal downregulates TNF-alpha gene expression in THP-1 human macrophages.

Oxidized lipoproteins inhibit TNF-alpha secretion by human THP-1 macrophages due, at least in part, to aldehydes derived from the oxidation of polyunsaturated fatty acids. This study extends these findings by investigating the effect of three aldehydes (2,4-decadienal (2,4-DDE), hexanal and 4-hydroxynonenal (4-HNE)) on TNF-alpha and IL-1beta mRNA expression. The 2,4-DDE and 4-HNE showed considerable biological activity which induced cytotoxicity on THP-1 macrophages at concentration of 50 microM. Hexanal, on the other hand, had a lower cytotoxic capacity and concentration of 1000 microM was needed for the effect to be observed. Exposure of THP-1 macrophages to aldehydes for 24 h inhibited TNF-alpha mRNA expression but increased or did not affect IL-1beta mRNA levels. The inhibitory action of 2,4-DDE was dose dependent and began at 5 microM (46%, P<0.001). The effect of 4-HNE was less inhibitory than 4-DDE but only when cytotoxic concentrations were used (50 microM). Very high concentrations of hexanal (200 microM) were needed to inhibit TNF-alpha expression (23%, P<0.001). This downregulation of TNF-alpha gene expression by 2,4-DDE was parallel to a lower protein production. These data indicate that low levels of 2,4-DDE may modulate inflammatory action by inhibiting TNF-alpha mRNA gene expression and that the biological activity of 2,4-DDE may be involved in the development of atherosclerosis.

Evidence against alterations in Lecithin:cholesterol acyltransferase (LCAT) activity in familial combined hyperlipidemia.

Elevated concentrations of plasma cholesterol and triglycerides are characteristic of familial combined hyperlipidemia (FCHL) which may also present with reduced high density lipoprotein (HDL) cholesterol concentrations. Lecithin:cholesterol acyltransferase (LCAT) plays a key role in reverse cholesterol transport by converting unesterified cholesterol to cholesterol ester in the process of maturation of HDL in the presence of its activator, apolipoprotein (apo) A-I. We hypothesised that alterations in LCAT activity or plasma concentrations or gene sequence of apo A-I could influence HDL metabolism in these patients. We studied cholesterol concentrations of high density lipoprotein subfractions and LCAT activity in 25 FCHL subjects and 48 controls. Total HDL (p=0.018) and HDL2 (p=0.008) were significantly decreased in the FCHL group compared with controls. After analyses with adjusted data only HDL2 remained significantly decreased in the FCHL group (p=0.050). The LDLc/HDLc and A-I/HDLc ratios were significantly elevated in the FCHL group (p <0.0001), the latter suggesting the existence of compositional differences in the HDL particles of the FCHL individuals. LCAT activity assessed in the FCHL (19.94+/-3.95 nmol/ml per h) and control (20.13+/-6.86 nmol/ml per h) groups showed no statistically significant differences. A significant positive correlation of LCAT activity with total HDL (r=0.42), HDL3 cholesterol (r=0.46) and apolipoprotein A-I (r=0.47) was observed in affected subjects but not in controls. An association between a Ga(-75)-A variation in the promoter region of the apo A-I gene and elevated concentrations of apo A-I (p=0.009) and apo C-III (p=0.041) was observed. This association was strongly influenced by the status of the subject providing further evidence for a regulatory role of this genetic region in the expression of FCHL. Our data suggests that LCAT activity is normal in FCHL and, therefore, does not account for the abnormalities observed in these patients essentially with regard to the HDL2 subfraction.

Simvastatin decreases aldehyde production derived from lipoprotein oxidation.

Treatment with statins are known to lower plasma and low-density lipoprotein (LDL) cholesterol levels with resultant prevention and regression of atherosclerosis. It has been recently suggested that the action of the statins may also have a direct effect on other mechanisms involved in the atherosclerotic plaque formation. Thus, we investigated whether simvastatin could have an antioxidant effect on plasma lipoproteins. The rate of oxidation of LDL and high-density lipoproteins (HDL) was measured by conjugated diene formation with and without the addition of increasing concentrations of simvastatin (in vitro) and in patients with and without treatment with simvastatin (in vivo). A strong correlation was observed between increasing simvastatin concentration and the lag phase, a negative correlation was observed for maximal rate and maximum diene production in LDL samples (r2 = +0.97, p <0.0001; r2 = -0.92, p <0.0001; r2 = -0.98, p <0.0001, respectively). For HDL no clear correlation could be established with the lag phase, but a strong negative correlation was also observed between simvastatin concentration and maximal rate and maximum diene production (r2 = -0.69, p <0.01; r2 = -0.98, p <0.0001, respectively). After 6 hours of oxidation the production of aldehydes in LDL and HDL was lower (30% and 5%, respectively) in samples obtained during simvastatin therapy with respect to those obtained without treatment. The 2,4-decadienal showed a decrease of 37% and 64% (p <0.05) in both oxidized-LDL and oxidized-HDL particles, respectively, with simvastatin treatment. Our findings demonstrate that simvastatin acts as an antioxidant in lipoprotein particles and, together with its lipid-lowering properties, could play an important role in preventing atherosclerosis.

Supplementation with vitamin E and/or zinc does not attenuate atherosclerosis in apolipoprotein E-deficient mice fed a high-fat, high-cholesterol diet.

Ever since oxidation has been known to be involved in atherogenesis, antioxidants have received considerable attention as potential antiatherogenic agents. The lipid-soluble vitamin E is the main antioxidant carried by lipoproteins. Zinc is a water-soluble trace element that acts as a cofactor of superoxide dismutase (SOD) and has an antioxidant role in several oxidative processes. To test the hypothesis that zinc could adjuvate the antioxidant activity of vitamin E and diminish atherogenesis, we explored how supplementing diet with vitamin E and/or zinc would affect an atherosclerosis-prone animal like Apo E-deficient mice. The increased plasma concentrations of both vitamin E and zinc showed that absorption was high. They had a significant hypolipidemic effect and the supplemented animals had 25% less plasma cholesterol and triglyceride than controls. The SOD activity was significantly higher in washed erythrocytes from mice supplemented with zinc. The plasma of supplemented animals was also significantly more resistant to oxidation. The size of lesions in the proximal aortic region did not differ among groups. Therefore, dietary supplementation resulted in the expected antioxidant effects but there was no substantial attenuation of atherosclerosis in this particular model.

[Anomalous origin of the right pulmonary artery from the ascending aorta. Its echo-Doppler diagnosis]. / Origen anómalo de la arteria pulmonar derecha desde la aorta ascendente. Diagnóstico eco-Doppler.

The anomalous origin of the right pulmonary artery from the ascending aorta is a rare malformation. Its diagnosis and early surgical treatment are necessary to avoid its fatal outcome. We present the pulsed and color echo-Doppler findings in a patient with this pathology.

[Left aorto-ventricular tunnel. Diagnosis with transthoracic and transesophageal echo-Doppler]. / Túnel aorto-ventricular izquierdo. Diagnóstico mediante eco-Doppler transtorácica y transesofágica.

Aortic-left ventricular tunnel is an infrequent congenital heart lesion consisting of an abnormal tubular-shaped communication between the aortic root and the left ventricle that bypasses the aortic valve. It is clinically undistinguishable from aortic insufficiency. Its prompt and precise diagnosis is crucial since early surgical treatment is definitely indicated, in contrast to aortic insufficiency. In our case, two-dimensional and pulsed color-flow Doppler imaging established the diagnosis, and the transesophageal approach was a great aid in detecting the aortic opening with its turbulent diastolic flow, and in tracing its intramyocardial course. This paper may be of interest not just as a new case-report but insofar as it stresses how importantly the transthoracic and transesophageal echocardiographic and Doppler scanning contributes to its diagnosis and therapeutic indication.

[The follow-up of transposition of the great arteries corrected by Senning's technic]. / Seguimiento de la transposición de grandes arterias corregida con técnica de Senning.

INTRODUCTION AND OBJECTIVES: The incidence of late complications after a physiological correction of the patients with transposition of the great arteries (D-TGA) is very significant, due to the alternative operation of the arterial switch. METHODS: We studied 125 patients with D-TGA, treated with Senning surgical correction between december of 1978 and november of 1990. Surgery was performed at a mean age of 11.7 months (from 7 days to 11.2 years), and the postoperative mean follow-up was 7.3 years (from 1.4 to 14.3 years). We analyzed their evolutive clinical condition, ECG, Holter and echocardiogram-Doppler. Four groups were defined: A) Simple, 48.8%. B) Associated with ventricular septal defect, 22.4%. C) With pulmonary stenosis, 15.2%. D) Both anomalies, 13.6%. RESULTS: Sixteen children died (12.8%), 11 of them on the postoperative period. The remaining 5 patients died, at a mean time of 34.3 months after surgery, because they were in cardiac failure. All of patients had enlargement of right ventricle and tricuspid regurgitation was observed in 39 children. There were 3 reoperations. Atrioventricular block was observed in 5.7% of the patients, 33.3% were not in sinus rhythm, 6.6% had atrial flutter-fibrillation, sinus node dysfunction was observed in 24.7%, and five permanent pacemakers were implanted (4.7%). CONCLUSIONS: The later mortality is not high, and the clinical outcome is good, but the frequent rhythm disturbances and enlargement of the right ventricle could let us conclude the hypothesis that anatomical correction is an optimal alternative procedure.

[Total anomalous pulmonary venous return in children: importance of echocardiographic diagnosis and early surgery]. / Retorno venoso pulmonar total anómalo en pediatría: importancia del diagnóstico ecocardiográfico y de la cirugía precoz.

OBJECTIVE: We studied patients who underwent surgical repair for total anomalous pulmonary venous return at our hospital. We report the importance of diagnosis by echocardiographic imaging before surgical treatment. METHODS: Within the period of 1990-1999, fourteen patients underwent surgical repair of this cardiopathy in our hospital. The type of anomalous drainage was supracardiac in 6 patients, infracardiac in 4, to the coronary sinus in 1, and mixed-type in 3 patients. Eleven cases were diagnosed with an echo-Doppler study, the findings being confirmed intraoperatively. RESULTS: There were 2 early deaths: one occurred in the operating room in a patient with a small left ventricle, and the second one was 35 days postoperatively as a result of a septic complication. Early in the postoperative period our primary goal has steadily been the control and treatment of pulmonary hypertension. After a mean follow-up time of 50 months, only 1 patient needed to be reoperated on and the remainder are symptomless. CONCLUSIONS: That sufficient diagnostic data on total anomalous pulmonary venous return can reliably be obtained by ultrasound scanning so that surgery can be promptly undertaken, and that its surgical risk is currently low and mid-term post-repair outcome is fairly good.

[Familial auricular fibrillation]. / Fibrilación auricular familiar.

INTRODUCTION AND OBJECTIVE: We present two families with atrial fibrillation in 20 of 50 members, during three generations, with known cardiac rhythms, in order to communicate their infrequent existence and the most relevant clinical facts. METHOD: Clinical situation, evolution, ECG and ECHO findings, treatments and complications related with the disease are investigated. RESULTS: The presence of atrial fibrillation in 20 members is demonstrated, although one of them was on sinus rhythm at the time of the study; 3 patients had left ventricular enlargement on the ECHO study; the clinical situation was good in all patients except two who died because of complications related to the arrythmia and a third patient that had a brain stroke. The patients received different treatments because they where controlled by different physicians; the possible lethal proarrythmic effect in such cases must be taken into account. CONCLUSION: Familiar atrial fibrillation is a very infrequent arrythmia, usually well tolerated, that follows a dominant autosomic hereditary pattern. The use of antiagregants is advised because of the risk of embolism, or the use of anticoagulants in the presence of associated risk factors. Electric cardioversion has been show not be useful. The possible proarrythmic effect of some antiarrythmic agents, used in the control of cardiac frequency, must be taken into account.

[Double-outlet left ventricle with subaortic interventricular defect and pulmonary stenosis: surgical correction with cryopreserved aortic homograft]. / Doble salida ventricular izquierda con comunicación interventricular subaórtica y estenosis pulmonar: corrección quirúrgica con utilización de homoinjerto aórtico crioconservado.

Double outlet left ventricle with subaortic ventricular septal defect and pulmonary stenosis is a very rare congenital heart disease. We present a case of this cardiopathy which underwent correction consisting of ventricular septal defect closure and right ventricular outflow tract reconstruction using a cryopreserved aortic homograft, with a postsurgical follow-up time of 18 months.