Methodology for the induction of myocardial infarction and cardiac function evaluation.

Cardiovascular disease (CVD) is the main cause of death worldwide, with myocardial infarction (MI) being the most prevalent pathology involved in CVD. MI is characterized by a deficiency in oxygen supply to the myocardium, thereby promoting ventricular remodeling of the ischemic and remote zone of the heart. Cardiac remodeling associated with MI could promote the development of heart failure and finally death. For these reasons, it is important to develop animal models that mimic human cardiac disease which could help to identify new mechanisms involved in the pathology and, consequently, develop new therapeutic strategies. We herein describe in detail a protocol for MI induction with low mortality rate (<15%) in rats by ligation of the left anterior descending artery. In addition, we also describe two imaging techniques which allow to evaluate cardiac structure and function-including deformation parameters in rats such as transthoracic echocardiography and cardiac magnetic resonance. This animal model could be useful for acute and chronic studies and for evaluating the potential usefulness of different treatments.

First case report of multivisceral transplant from a deceased cardiac death donor.

The current shortage of pediatric multivisceral donors accounts for the long time and mortality on the waiting list of pediatric patients. The use of donors after cardiac death, especially after the outbreak of normothermic regional perfusion, has increased in recent years for all solid organs except the intestine, mainly because of its higher susceptibility to ischemia-reperfusion injury. We present the first literature case of multivisceral donors after cardiac death transplantation in a 13-month-old recipient from a 2.5-month-old donor. Once exitus was certified, an extracorporeal membrane oxygenation circuit was established, cannulating the aorta and infrarenal vena cava, while the supra-aortic branches were clamped. The abdominal organs completely recovered from ischemia through normothermic regional perfusion (extracorporeal membrane oxygenation initially and beating heart later). After perfusion with the preservation solution, the multivisceral graft was uneventfully implanted. Two months later, the patient was discharged without any complications. This case demonstrates the possibility of reducing the time spent on the waiting list for these patients.

Mitochondrial Oxidative Stress Promotes Cardiac Remodeling in Myocardial Infarction through the Activation of Endoplasmic Reticulum Stress.

We have evaluated cardiac function and fibrosis in infarcted male Wistar rats treated with MitoQ (50 mg/kg/day) or vehicle for 4 weeks. A cohort of patients admitted with a first episode of acute MI were also analyzed with cardiac magnetic resonance and T1 mapping during admission and at a 12-month follow-up. Infarcted animals presented cardiac hypertrophy and a reduction in the left ventricular ejection fraction (LVEF) and E- and A-waves (E/A) ratio when compared to controls. Myocardial infarction (MI) rats also showed cardiac fibrosis and endoplasmic reticulum (ER) stress activation. Binding immunoglobulin protein (BiP) levels, a marker of ER stress, were correlated with collagen I levels. MitoQ reduced oxidative stress and prevented all these changes without affecting the infarct size. The LVEF and E/A ratio in patients with MI were 57.6 ± 7.9% and 0.96 ± 0.34, respectively. No major changes in cardiac function, extracellular volume fraction (ECV), or LV mass were observed at follow-up. Interestingly, the myeloperoxidase (MPO) levels were associated with the ECV in basal conditions. BiP staining and collagen content were also higher in cardiac samples from autopsies of patients who had suffered an MI than in those who had died from other causes. These results show the interactions between mitochondrial oxidative stress and ER stress, which can result in the development of diffuse fibrosis in the context of MI.

A Bicentric Propensity Matched Analysis of 158 Patients Comparing Porcine Versus Bovine Stented Bioprosthetic Valves in Pulmonary Position.

BACKGROUND AND OBJECTIVES: Pulmonary valve replacement (PVR) is the most common operation in adults with congenital heart disease (CHD). There is controversy regarding the best bioprosthesis. We compare the performance of stented bioprosthetic valves (the Mosaic [Medtronic™] porcine pericardial against Carpentier Perimount Magna Ease [Edwards™] bovine) in pulmonary position in patients with CHD. METHODS: Between January 1999 and December 2019, all the PVRs were identified from hospital databases in 2 congenital heart centres in Spain. Valve performance was evaluated using clinical and echocardiographic criteria. Propensity score matching was used to balance the 2 treatment groups. RESULTS: Three hundred nineteen patients were retrospectively identified. After statistical adjustment, 79 propensity-matched pairs were available for comparison Freedom from reintervention for the porcine cohort was 98.3%, 96.1%, and 91.9% at 3, 5, and 10 years and 100%, 98%, and 90.8% for the bovine cohort (p=0.88). Freedom from structural valve degeneration (SVD) for the porcine cohort was 96.9%, 92.8% and 88.7% at 3, 5, and 10 years and 100%, 98%, and 79.1% for the bovine cohort (p=0.38). Bovine prosthesis was associated with a reintervention hazard ratio (HR), 1.12; 95% confidence intervals (CIs), 0.24-5.26; p=0.89 and SVD HR, 1.69 (0.52-5.58); p=0.38. In the first 5 years, there was no difference in outcomes. After 5 years, the recipients of the bovine bioprosthesis were at higher risk for SVD (reintervention HR, 2.08 [0.27-16.0]; p=0.49; SVD HR, 6.99 [1.23-39.8]; p=0.03). CONCLUSIONS: Both bioprosthesis have similar outcomes up to 5 years, afterwards, porcine bioprosthesis seem to have less SVD.

Perspectivas actuales en el procedimiento de Ross y Ross-Konno: ¿es hora de buscar alternativas? / Current perspectives in Ross and Ross-Konno procedures: Is it time to search for alternatives?

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Role of endoplasmic reticulum stress in renal damage after myocardial infarction.

Myocardial infarction (MI) is associated with renal alterations resulting in poor outcomes in patients with MI. Renal fibrosis is a potent predictor of progression in patients and is often accompanied by inflammation and oxidative stress; however, the mechanisms involved in these alterations are not well established. Endoplasmic reticulum (ER) plays a central role in protein processing and folding. An accumulation of unfolded proteins leads to ER dysfunction, termed ER stress. Since the kidney is the organ with highest protein synthesis fractional rate, we herein investigated the effects of MI on ER stress at renal level, as well as the possible role of ER stress on renal alterations after MI. Patients and MI male Wistar rats showed an increase in the kidney injury marker neutrophil gelatinase-associated lipocalin (NGAL) at circulating level or renal level respectively. Four weeks post-MI rats presented renal fibrosis, oxidative stress and inflammation accompanied by ER stress activation characterized by enhanced immunoglobin binding protein (BiP), protein disulfide-isomerase A6 (PDIA6) and activating transcription factor 6-alpha (ATF6α) protein levels. In renal fibroblasts, palmitic acid (PA; 50-200 µM) and angiotensin II (Ang II; 10-8 to 10-6M) promoted extracellular matrix, superoxide anion production and inflammatory markers up-regulation. The presence of the ER stress inhibitor, 4-phenylbutyric acid (4-PBA; 4 µM), was able to prevent all of these modifications in renal cells. Therefore, the data show that ER stress mediates the deleterious effects of PA and Ang II in renal cells and support the potential role of ER stress on renal alterations associated with MI.

Evolución neurológica y resultados de la cirugía pediátrica del arco aórtico mediante perfusión cerebral selectiva / Neurological changes and outcomes of paediatric surgery of the aortic arch using selective cerebral perfusion

INTRODUCCIÓN: Los objetivos son analizar las alteraciones neuropsicológicas a medio plazo de los niños intervenidos del arco aórtico mediante perfusión cerebral selectiva (PCS) y detectar posibles factores modificables en la técnica quirúrgica que pueden ayudar a minimizar la afectación neurológica posterior. MATERIAL Y MÉTODOS: Se establecieron como criterios de inclusión: patología del arco aórtico intervenida mediante PCS durante el primer año de vida, entre el 10 de agosto del 2004 y el 24 de mayo del 2016, fisiología biventricular y edad gestacional mayor de 31 semanas. En ausencia de cromosomopatía, se clasificaron desde el punto de vista neurológico siguiendo el modified Rankin score. En mayores de 4 años se realizaron estudios de inteligencia, nivel de atención, maduración y aptitudes psicolingüísticas. RESULTADOS: Se incluyeron ochenta y dos pacientes, cuya edad media en el momento de la cirugía fue de 1,8 meses. El flujo medio en PCS fue de 32 ml/kg/min. El tiempo medio de PCS fue de 31 min. La mortalidad global de la serie fue del 14,8%. Con disfunción neurológica se observaron un 35,9% y se detectaron como factores de riesgo: cirugía en menores de 10 días de edad, duración de PCS mayor de 40 min y la duración del enfriamiento o calentamiento. Un 35,2% de los pacientes mayor de 5 años fueron diagnosticados de déficit de atención. CONCLUSIONES: Los pacientes intervenidos en el primer año de vida con PCS precisan un seguimiento neuropsicológico y hay factores modificables quirúrgicos que pueden influir en el desarrollo neurológico

INTRODUCTION: The aims of this article are to analyse the neuropsychological changes in the medium-term in children subjected to aortic arch surgery using selective cerebral perfusion (SCP), as well as to detect any modifiable factors in the surgical technique that may contribute to minimising the subsequent neurological involvement. MATERIAL AND METHODS: Inclusion criteria were established as: aortic arch disease operated on using SCP during the first year of life, between 10 August 2004 and 24 May 2016, biventricular physiology, and gestational age greater than 31 weeks. In the absence of a chromosomal disease, they were classified, from a neurological point of view, using the Rankin score. Children over 4-years of age were subjected to intelligence studies, including attention level, development, and psycho-lingual skills. RESULTS: The study included a total of 82 patients with a mean age of 1.8 months. The mean SCP flow was 32 ml/kg/min. The mean time of SCP was 31 minutes. The overall mortality of the series was 14.8%. Neurological dysfunction was observed in 35.9% of patients, and the following were detected as risk factors: surgery in patients less than 10-days-old, duration of SCP greater than 40minutes, and the time required for the cooling down and/or warming-up. Attention deficit was diagnosed in 35.2% of patients greater than 5-years-old. CONCLUSIONS: Patients operated on using SCP in in the first year of life required a neuropsychological follow-up, and there are modifiable surgical factors that may have an influence on neurological development

[Neurological changes and outcomes of paediatric surgery of the aortic arch using selective cerebral perfusion]. / Evolución neurológica y resultados de la cirugía pediátrica del arco aórtico mediante perfusión cerebral selectiva.

INTRODUCTION: The aims of this article are to analyse the neuropsychological changes in the medium-term in children subjected to aortic arch surgery using selective cerebral perfusion (SCP), as well as to detect any modifiable factors in the surgical technique that may contribute to minimising the subsequent neurological involvement. MATERIAL AND METHODS: Inclusion criteria were established as: aortic arch disease operated on using SCP during the first year of life, between 10 August 2004 and 24 May 2016, biventricular physiology, and gestational age greater than 31 weeks. In the absence of a chromosomal disease, they were classified, from a neurological point of view, using the Rankin score. Children over 4-years of age were subjected to intelligence studies, including attention level, development, and psycho-lingual skills. RESULTS: The study included a total of 82 patients with a mean age of 1.8 months. The mean SCP flow was 32ml/kg/min. The mean time of SCP was 31minutes. The overall mortality of the series was 14.8%. Neurological dysfunction was observed in 35.9% of patients, and the following were detected as risk factors: surgery in patients less than 10-days-old, duration of SCP greater than 40minutes, and the time required for the cooling down and/or warming-up. Attention deficit was diagnosed in 35.2% of patients greater than 5-years-old. CONCLUSIONS: Patients operated on using SCP in in the first year of life required a neuropsychological follow-up, and there are modifiable surgical factors that may have an influence on neurological development.

External Validation of 3 Risk Scores in Adults with Congenital Heart Disease.

BACKGROUND AND OBJECTIVES: Adults with congenital heart disease (CHD) are an increasing group of patients thanks to the survival of over 85% of children with CHD. 20% of these patients shall warrant a surgical procedure during their life span. However, currently there is no one risk score that assess correctly the mortality of these procedures. Thus, we analyse the risk scores used at our institution. METHODS: From May 1991 till June 2017, 608 procedures in adults with CHD were performed. The 3 risk scores (risk adjustment for congenital heart surgery [RACHS-1], Aristotle, and Euroscore I) of each procedure were analysed. We used area under the receiver operating characteristic curve (c-index) to measure model discrimination, and Hosmer-Lemeshow (H-L) statistic along with calibration plots to measure calibration. RESULTS: There was no statistical difference between the area under the curve for the 3 scores (χ²=0.58 with 2 df, p=0.750). There was no evidence of lack of fit for RACHS-1 (H-L, χ²=2.61; p=0.271) and Aristotle score (H-L, χ²=5.69; p=0.459). However, there was evidence in lack of calibration in the Euroscore I scoring system (H-L, χ²=33.69; p<0.001). The calibration slope for RACHS-1 was 0.912, for Aristotle (stratified in risk groups) was -0.14 and for Euroscore 1 (stratified in risk groups) was 0.46. CONCLUSIONS: RACHS-1 seems to be best risk scoring system for calculating mortality applied to surgery in adults with CHD.

The Impact of Cardiac Lipotoxicity on Cardiac Function and Mirnas Signature in Obese and Non-Obese Rats with Myocardial Infarction.

Cardiac lipotoxicity is involved in the cardiac functional consequences associated with obesity. Therefore, the aim of this study was to explore whether changes in the mitochondrial lipid cardiac profile could reflect differences in cardiac function and structure in obese and non-obese rats with myocardial infarction (MI). Whether these changes can also be reflected in a specific plasma miRNA signature as markers of cardiac damage was also evaluated. Rats were fed with either standard (3.5% fat) or high fat diet (35% fat) for 6 weeks before the induction of MI and sacrificed 4 weeks later. MI showed cardiac lipotoxicity independently of the presence of obesity, although obese and non-obese rats did not present the same cardiac lipid profile at mitochondrial level. Several cardiac lipid species in mitochondria, including cardiolipins and triglycerides, were associated with myocardial fibrosis, with mitochondrial triglyceride levels being independently associated with it; this supports that lipotoxicity can affect cardiac function. MI down-regulated plasma levels of miRNA 15b-5p and 194-5p in obese and non-obese animals, which were associated with cardiac function, mitochondrial lipids and myocardial fibrosis, with miRNA 15b-5p levels being independently associated with cardiac fibrosis. This could support that lipotoxicity could affect heart function by modulating plasma miRNAs.

Superviviente a doble complicación mecánica tras el infarto: rotura del músculo papilar posteromedial y rotura contenida de pared libre / Survivor of a double mechanical complication after myocardial infarction: papillary muscle rupture and contained free-wall rupture

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Lugones' technique for correction of Scimitar syndrome.

Several surgical techniques have been described to channel the right pulmonary venous return to the left atrium in the Scimitar syndrome which includes direct reimplantation, graft interposition, or repair. Because these techniques can result in pathway obstruction, Lugones has devised a technique which uses in situ pericardium to construct a wide tunnel connecting the pulmonary venous return to the left atrium. We report the use of Lugones technique in an adult with Scimitar syndrome.

Membranous glomerulopathy in renal allograft: an ultrastructural study of 17 cases.

BACKGROUND: Membranous glomerulopathy is a common complication of renal allograft. However, its incidence and prognosis are not well defined, because an undetermined number of them pass undiagnosed under the generic epigraph of chronic allograft nephropathy. MATERIALS AND METHODS: To assess the diagnostic refinement supplied by electron microscopy to conventional light and immunofluorescence procedures the authors reviewed 17 cases of electron microscopy-confirmed membranous glomerulonephritis in kidney allograft. In addition, they searched for other features of graft injury, particularly lesions associated with alloimmune reaction, in order to evaluate the contribution of each lesion to the long-term outcome of the allograft. RESULTS: In 4 of the 17 cases of their series the diagnosis of membranous glomerulopathy was made by electron microscopy. In addition, in 5 samples, lesions of chronic alloimmune rejection were present (in 4 cases the diagnosis was based on electron microscopy findings). At the end point of the study, 3 of the 5 patients with chronic alloimmune injury were in dialysis, 1 had died with functioning allograft, and the fifth suffered severe renal failure but was not in dialysis. On the other hand, 3 of the 12 patients without evidence of alloimmune injury had returned to the dialysis program. CONCLUSIONS: Electron microscopy is a useful tool in the assessment of renal allograft pathology and can provide additional morphological features of prognostic relevance.