Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy.

The heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy.

Chemical interactions between Saturn's atmosphere and its rings.

The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.

Improvement of refractory pruritus after lipoprotein-apheresis in arthrogryposis-renal failure-cholestasis syndrome.

Accumulation of bile acids can lead to invalidating pruritus in cholestatic patients. Few reports exist on the influence of lipoprotein-apheresis (LA) on plasma level of total bile acids (tBA). We report of significant decrease in tBA levels and drastic improvement of pruritus in a 5-year-old girl with arthrogryposis-renal failure-cholestasis syndrome. We present LA as a suitable rescue treatment option in therapy-refractory cholestasis-associated pruritus, at least as bridge until a long-term solution such as entero-biliary anastomosis or transplantation is possible.

Desarrollo de la Nefrología Pediátrica en el Hospital Universitario Vall d´Hebron / Development of pediatric nephrolgy in the University Hospital Vall d´Hebron

El desarrollo de la nefrología pediátrica ha sido paralelo al significativo aumento de la superviciencia de niños y adolescentes con enfermedad renal en las últimas décadas. El Servicio de Nefrología Pediátrica del Hospital Universitario Vall d´Hebron (HUVH( es el servicio terciario de referencia de la subespecialidad en la red sanitaria pública de Catalunya e Islas Baleares. Los hitos más representativos en su historia han sido los siguientes: 1970 primera hemodiálisis (HD) pediátrica del Estado, 1981 primer transplante de riñon (TxR) pediátrico, 1994 primer traspaltne hepato-renal del Estado y 2008 acreditación como unidad de referncia CSUR para TxR pediátrico. En la actualidad, la actividad clínica del servicio se focaliza en los programs de TxR, diálisis, enfermedad renal crónica (ERC) y enfermedades renales minoritarias del niño y adolescente. Asimsimo, el servicio realiza una intensa actividad docente e investigadora en el campo de la subespecialidad. Los principales retos actuales son los progrmas de cronicidad específicos, y la transferencia protocolizada de los adolescentes a los servicios de nefrología de adultos (AU)

Pediatric Nephrology discipline has been developed simultaneously with the remarkable improvement of life expectancy occurred in children and adolescentes with renal disease during the past decades. The Pediatric Nephrology Service of the Universitary Hospital Vall d´Hebron (HUVH) is the major service of the public health system for Catalunya and Balear Islands in the subspeciality. The most representative milestones of the Sevice were: first pediatric hemodialisis (HD) in Spain in 1970; first peditric kidney transplant (KTx) in1981; first combined liver and kidney transplant in the country in 1994, and acreditation as reference center CSUR for pediatric KTx in 2008. Currently, clinical activity is mostly focused on KTx, dialysis, chronic kidney disease, and rare renal diseases in children and adolescents. Further, the service is active in teaching and research in the field. Major current chalenges are the development of chronicity programmes and protocolized transfer of care of adolescents from pediatric to adult Nephrology Services (AU)

Delayed graft function is reduced with antithymocyte globulin induction in pediatric kidney transplantation.

Reduction of delayed graft function (DGF) is critical to the success of renal transplantation. We report graft outcomes with antithymocyte globulin (ATG) induction compared with using interleukin-2 receptor antagonist basiliximab (IL-2RA). Twelve pediatric patients received a pediatric deceased donor kidney. We treated them with ATG (group A, ATG; n = 6) or IL-2RA (group B, n = 6). DGF was observed in 0 cases (group A) and in 6 cases (group B), which showed a mean of 7 +/- 3 days (P < .001). In group A, lymphopenia occurred routinely resolving after 3-6 months, none with serious infection. The incidence of opportunistic infections was 0% in both groups. One-year patient and graft survivals were 100% in both groups. ATG induction significantly reduced the incidence of delayed graft function. Both induction treatments led to a good patient and graft survival.

Blood warm reperfusion: a necessary adjunct to heart-valve surgery in low-risk patients?

AIM: The aim of this prospective, randomized study was to determine whether blood warm reperfusion improves myocardial protection provided by cold crystalloid cardioplegia in patients undergoing first-time elective heart-valve surgery, using cardiac troponin I release as the criterion for evaluating the adequacy of myocardial protection. METHODS: Seventy patients with a left ventricular ejection fraction greater than 40% were randomly assigned to 1 of 2 myocardial protection strategies: 1) cold crystalloid cardioplegia with no reperfusion or 2) cold crystalloid cardioplegia followed by 2-minute blood warm reperfusion before aortic unclamping. Cardiac troponin I concentrations were measured in serial venous blood samples drawn immediately prior to cardiopulmonary bypass and after aortic unclamping at 6, 9, 12, and 24 h. RESULTS: Randomization produced 2 equivalent groups. The total amount of cardiac troponin I released (7.17+/- 14.8 mg in the crystalloid cardioplegia with no reperfusion group and 5.82+/-4.66 mg in the crystalloid cardioplegia followed by blood warm reperfusion group) was not different (P > 0.2). Cardiac troponin I concentration did not differ for any sample in either of the 2 groups. The total amount of cardiac troponin I released was higher in patients who required inotropic support (9.14 +/-16.2 mg) than those who did not (4.73+/-4.52 mg; P = 0.009). CONCLUSIONS: Our study shows that adding blood warm reperfusion to cold crystalloid cardioplegia provides no additional myocardial protection in low-risk patients undergoing heart-valve surgery.

Tratamiento con metformin en pacientes con enfermedad hepática grasa no alcoholica portadores de resistencia a la insulina / Treatment with metformin in patient with nonalcoholic steatohepatitis disease carrier of insuline resistance

Determinar si el tratamiento con metformin modifica los valores de aminotransferasas séricas y la histología hepática en pacientes con enfermedad hepática grasa no alcoholica (EHGNA) y Resistencia a la insulina (RI). 22 pacientes con diagnóstico histológico de EHGNA, RI y transaminasas elevadas recibieron tratamiento con metformin 1000 mg/día. Fueron seguidos por tres meses (n: 4), seis meses (n:4, nueve meses (n:7) y 12 (n:7), con controles trimestrales de aminotransferasas y control histológico al año. Utilizamos t de student pareada y análisis de varianza, p<0.05. La TGo disminuyó en 9 pacientes, y se normalizó en 11; la TGP disminuyó en 9 pacientes y se normalizó también en 9 pacientes, siendo estadísticamente significante en el grupo seguido por seis (p=0,007) y doce meses (p=0.02). Al tercer mes de seguimiento en todos los pacientes disminuyeron la TGO (84,5 a 37,04; p=0,000037) y la TGP (137,27 a 72,95; p=0,0019067). Se repitió la biopsia herpática post-tratamiento en 3 pacientes. En uno disminuyó el grado de 2 a 1 sin cambios en el estadio y en los otros dos no cambió ni el grado ni estadío. El metformin disminuyó las aminotransferasas séricas significatntemente llegando a normalizarse los valores en la mitad de los pacientes tratados. No podemos establecer conclusdiones sobre los efectos del metformin en la histología hepática por el pequeño número de pacientes con biopsia hepática post-tratamiento

["Mammary loop" technique--new method of multiple coronary revascularization using internal mammary arteries]. / Tehnica "buclei mamare" o noua metoda de revascularizare coronara multipla folosind arterele mamare interne.

The internal mammary arteries are "the gold standard" conduits for coronary by-pass because their' s patency is superior to the saphenous graft. There are some surgical techniques which allow to use the entire length of the mammary arteries: the Y graft, the T graft and the pi graft. We describe recently the "mammary loop" technique that allows to make a Y graft using only one internal mammary artery. This technique also simplifies the construction of a pi graft. In this article we present the variants of this technique and discuss the indications and our early experience results.

[Myocardial microdialysis. Importance and potential in cardiovascular research]. / Microdialyse myocardique. Intérêt et potentiel en recherche cardio-vasculaire.

The microdialysis expanded mainly in the field of the neuro- and the dermopharmacology with the study of the transmitters released in the central nervous system and derm. Since ten years, this tool gained other disciplines such as cardiology and cardiovascular surgery. Indeed, the collection and the study of the molecules released in the myocardic interstitial fluid without deteriorating it functioning made microdialysis a powerful tool in the study of the extracellular environment of the cardiomyocyte. The purpose of this study is to point out the principle of the microdialysis and to show its various uses in the field of cardiovascular pharmacology.

Endovascular treatment of the traumatic rupture of the aortic isthmus.

The traumatic rupture of the aortic isthmus is a dehiscence of all or part of the aortic wall, occurring as a result of a closed thoracic trauma. Standard surgical technique requires left thoracotomy, aortic cross-clamping and use of the cardiopulmonary by-pass to prevent ischemic complications, in special the neurologic and visceral ones. The endovascular treatment of these lesions is a more simple solution and there are recent reports on the stent-grafting of the isthmic rupture of the thoracic aorta. We report three cases of successful endovascular repair of the aortic isthmic rupture and we discuss the emergency indications, the advantages and the limits of this technique.

[Effects of nitric oxide on cardioprotection prior to ischemia-reperfusion]. / Effets du monoxyde d'azote sur la cardioprotection avant l'ischémie-reperfusion.

This study aimed at evaluating the role of nitric oxide (NO) when generated 24 h prior to ischemia-reperfusion. Three groups were studied in an isolated buffer-perfused heart model: Control (saline = 3.3 mL/kg, n = 10), the precursor of NO, L-arginine, (500 mg/kg, n = 10) and an inhibitor of NO synthase, L-NAME, (10 mg/kg, n = 9). All groups were injected intraperitoneally 24 h before heart extraction. Nitrites, nitrates (an index of nitric oxide release) and cardiac troponine I were assayed. During the reperfusion period, there was a low release of nitric oxide and cardiac troponine I associated with improved recovery of post-ischemic myocardial function. These results indicate that in this model, the pre-treatment improved myocardial function and thus, NO could play a role as a trigger and not as a mediator of cardioprotection.

False lumen patency as a predictor of late outcome in aortic dissection.

Aortic dissection (AD) is a disease with a high-risk of mortality. Late deaths are often related to complications in nonoperated aortic segments. Between 1984 and 1996, we retrospectively analyzed the data of 109 patients with acute AD (81 men and 28 women; average age 61 +/- 14 years). All imaging examinations were reviewed, and a magnetic resonance imaging examination was performed at the time of the study. Aortic diameters were measured on each aortic segment. Predictive factors of mortality were determined by Cox's proportional hazard model, in univariate and multivariate analyses, using BMDP statistical software. Follow-up was an average of 44 +/- 46 months (range 24 to 164). Actuarial survival rates were 52%, 46%, and 37% at 1, 5, and 10 years, respectively, for type A AD versus 76%, 72%, and 46% for type B AD. Predictors of late mortality were age >70 years and postoperative false lumen patency of the thoracic descending aorta (RR 3.4, 95% confidence intervals 1.20 to 9.8). Descending aorta diameter was larger when false lumen was patent (31 vs 44 mm; p = 0.02) in type A AD. Furthermore, patency was less frequent in operated type A AD when surgery had been extended to the aortic arch. Thus, patency of descending aorta false lumen is responsible for progressive aortic dilation. In type A AD, open distal repair makes it possible to check the aortic arch and replace it when necessary, decreases the false lumen patency rate, and improves late survival.

Effects of L-arginine administration before cardioplegic arrest on ischemia-reperfusion injury.

BACKGROUND: Administration of L-arginine during reperfusion or its addition to cardioplegic solution has been shown to protect myocardium against ischemia-reperfusion injury. This study aimed at evaluating the role of L-arginine in ischemia-reperfusion injury when administered intraperitoneally 24 hours before cardioplegic arrest. METHODS: Two groups of Sprague-Dawley rats (control, n = 10; and L-arginine, n = 10) were studied in an isolated buffer-perfused heart model. Both groups were injected intraperitoneally 24 hours before ischemia. Before experimentation blood samples were collected for cardiac troponin I and cGMP analysis. In the coronary effluents, cardiac troponin I, adenosine, cyclic guanosine monophosphate, and nitric oxide metabolites were assayed. RESULTS: Before heart excision, serum cardiac troponin I concentrations were higher in the L-arginine than in the control group (0.037 +/- 0.01 versus 0.02 +/- 0.05 microg x L(-1); p < 0.05). During reperfusion, cardiac troponin I release was lower in the L-arginine than in the control group (0.04 +/- 0.01 versus 0.19 +/- 0.03 ng x min(-1); p < 0.05). The coronary flow as well as the left ventricular developed pressure were higher in the L-arginine than in the control group before ischemia and remained so throughout the experimentation. CONCLUSIONS: These results indicate that L-arginine administered intraperitoneally 24 hours before cardioplegic arrest reduced myocardial cell injury and seems to protect myocardium against ischemia-reperfusion injury.

Myocardial fixation of anticardiac troponin I antibody and cardiac troponin I release.

BACKGROUND: The threefold aim of this experimental study was to test the correlation of cardiac troponin I released to myocardial infarction size and myocardial fixation of anticardiac troponin I antibody and to determine how long after myocardial infarction the measure of cardiac troponin I concentration can evaluate myocardial infarction size. METHODS: Forty rabbits were assigned either to a control group or to an experimental preconditioned group. Infarction was obtained by tightening a snare around the left anterior descending artery. Serial venous blood samples were drawn for measurement of cardiac troponin I. The rabbits were sacrificed at 72 hours and a histological study was performed to determine the infarct size and the size of the area void of fixation of anticardiac troponin I antibody. RESULTS: There was a linear correlation between the total amount of CTn I released and both infarct size (r=0.45, p<0.02) and the size of the area void of anti-cardiac troponin I antibody (r=0.47, p<0.02). These two sizes were strongly correlated (r=0.95, p<0.02). The hour 9 CTn I sample was the best correlated with both the infarct size (r=0.47, p<0.02) and the size of area void of anticardiac troponin I antibody (r=0.45, p<0.02). CONCLUSIONS: Our study shows that: 1) cardiac troponin I release is correlated to both myocardial infarction size and the size of area void of fixation of anticardiac troponin I antibody, 2) the area void of anticardiac troponin I antibody fixation includes the whole ischemic area, and 3) evaluation of myocardial infarction size can be obtained by CTn I concentration as early as the ninth hour.

Perceived health status in patients over 70 before and after open-heart operations.

AIM: to evaluate improvement and predictors of improvement in patients' perceived health status after cardiac surgery in older patients. METHODS: three hundred and seventy-seven patients from three different departments of cardiac surgery completed the Nottingham Health Profile questionnaire before and 1 and 2 years after open-heart surgery. We analysed pre- and postoperative data and pre- and postoperative Nottingham Health Profile scores. RESULTS: the mean age was 74+/-3 years. The comparison between pre- and postoperative scores showed an improvement in all but the social isolation section. Logistic regression showed that the predictors of patients who became worse after surgery were (i) in the energy section: age over 75 [odds ratio (OR) = 1.8, 95% confidence interval (CI) = 1.02-3.2], coronary artery disease (OR = 2.4, 95% CI = 1.04-3.6) and postoperative events (OR = 1.9, 95% CI = 1.01-3.7); (ii) in the physical mobility section: diabetes mellitus (OR = 2.4, 95% CI = 1.2-4.7); and (iii) in the social isolation section: physical mobility impairment (OR = 3.4, 95% CI = 1.3-8.7). CONCLUSIONS: cardiac surgery improves perceived health status in patients over 70. This improvement is better for those undergoing aortic valve replacement than for those undergoing coronary artery bypass surgery. Comparison with reference scores for a standard population shows that, even when successful, cardiac surgery results in fatigue and persistent sleep disturbance in older patients.

Preoperative quality of life as a predictive factor of 3-year survival after open heart operations.

BACKGROUND: The aim of this prospective study was twofold: to determine the evolution of quality of life in heart surgery patients through the first 3 postoperative years using the Nottingham Health Profile questionnaire and to determine whether preoperative quality of life influences 3-year survival. METHODS: From January to July 1994, 215 patients underwent elective open heart operation in our department. Patients filled in the Nottingham Health Profile questionnaire five times: preoperatively, postoperatively at month 3, and at each anniversary of their operation for 3 years. The evolution of quality of life scores through time were compared using analysis of covariance with repeated measures. Analysis of 3-year survival prognostic factors was achieved using the Cox proportional hazards model. RESULTS: Quality of life scores varied through time, but not significantly. Multivariate analysis showed two independent risk factors to influence 3-year survival: dyspnea class (III-IV versus I-II, relative risk = 2.80, 95% confidence interval = 1.2 to 6.5) and the energy section of the Nottingham Health Profile questionnaire (relative risk = 1.02 by unit, 95% confidence interval = 1.01 to 1.03). CONCLUSIONS: Our study shows quality of life scores to be stable for the first 3 years after operation and the preoperative energy score to be predictive of 3-year survival.

Intermediate lukewarm (20 degrees c) antegrade intermittent blood cardioplegia compared with cold and warm blood cardioplegia.

BACKGROUND: In the field of intermittent antegrade blood cardioplegia, 3 levels of temperature are commonly used: (1) cold (8 degrees C); (2) tepid (29 degrees C); and (3) warm (37 degrees C). Given the 21 degrees C spread and the metabolic changes that can occur between cold (8 degrees C) and tepid (29 degrees C) cardioplegia, we thought it worthwhile to test a temperature halfway between the cold and tepid levels. The aim of this study was to test the quality of myocardial protection provided by intermediate lukewarm (20 degrees C) cardioplegia by comparing it with cold and warm cardioplegia. Protection was assessed by measuring cardiac troponin I release. METHODS: One hundred thirty-five patients undergoing coronary artery bypass grafting were enrolled in a prospective randomized trial comparing cold (8 degrees C), intermediate lukewarm (20 degrees C), and warm (37 degrees C) antegrade intermittent blood cardioplegia. Cardiac troponin I concentrations were measured in serial venous blood samples. RESULTS: The total amount of cardiac troponin I released was significantly higher in the cold group (4.7 +/- 2.3 microg) than in the intermediate lukewarm (3.4 +/- 2.0 microg) or the warm (3.1 +/- 2.7 microg) groups. The cardiac troponin I concentration was significantly higher at hour 6 in the intermediate lukewarm group (1. 23 +/- 0.55 microg/L) than in the warm group (0.89 +/- 0.50 microg/L). CONCLUSIONS: Intermittent antegrade intermediate lukewarm blood cardioplegia is appropriate and clinically safe. Cardiac troponin I release suggests that intermediate lukewarm cardioplegia is better than cold cardioplegia but less effective than warm cardioplegia in low-risk patients. We therefore recommend the use of warm cardioplegia in low-risk patients.

Determination of cardiac troponin I forms in the blood of patients with acute myocardial infarction and patients receiving crystalloid or cold blood cardioplegia.

To determine the forms of cardiac troponin I (cTnI) circulating in the bloodstream of patients with acute myocardial infarction (AMI) and patients receiving a cardioplegia during heart surgery, we developed three immunoenzymatic sandwich assays. The first assay involves the combination of two monoclonal antibodies (mAbs) specific for human cTnI. The second assay involves the combination of a mAb specific for troponin C (TnC) and an anti-cTnI mAb. The third assay was a combination of a mAb specific for human cardiac troponin T (cTnT) and an anti-cTnI mAb. Fifteen serum samples from patients with AMI, 10 serum samples from patients receiving crystalloid cardioplegia during heart surgery, and 10 serum samples from patients receiving cold blood cardioplegia during heart surgery were assayed by the three two-site immunoassays. We confirmed that cTnI circulates not only in free form but also complexed with the other troponin components (TnC and cTnT). We showed that the predominant form in blood is the cTnI-TnC binary complex (IC). Free cTnI, the cTnI-cTnT binary complex, and the cTnT-cTnI-TnC ternary complex were seldom present, and when present, were in small quantities compared with the binary complex IC. Similar results were obtained in both patient populations studied. These observations are essential for the development of new immunoassays with improved clinical sensitivity and for the selection of an appropriate cTnI primary calibrator.