[Cardiac surgery in elderly patients]. / Cirugía cardíaca en el anciano.

OBJECTIVE: The morbimortality of elderly patients, (age 70 years or older), who underwent surgery for valvular and coronary artery disease in the last 17 years was analyzed. PATIENTS AND METHOD: A total of 1,305 patients (654 valvular, 531 coronary and 120 combined) operated from January 1985 to December 2000 were retrospectively studied. Mean age was 73.7 years. We analyzed the progression of the pathology, comorbidity, and results. A second retrospective analysis was made of patients who underwent surgery in the last three years (436 patients) to determine the relation between preoperative comorbidity and postoperative evolution. RESULTS: The mean hospital mortality was 16% (18% valvular, 11% coronary artery, and 23% combined). In the last three years this mortality was reduced to 11% (15.17, 6.26, and 16.18%, respectively) despite an increase in comorbidity. Comorbidity and complications increased with age (p < 0.05). Mean hospital stay was 15.5 days and the stay in intensive/semi-intensive care was 5 days. Independent risk factors of postoperative complications were creatinine levels > 2 mg/dl, combined surgery, and prior surgery. Predictors of death were prior surgery, valvular surgery, and combined surgery, with a clear tendency in the case of obesity. The presence of any complication in the postoperative period (renal or respiratory failure, infections, or myocardial infarction) was an independent predictor of mortality. Off-pump coronary surgery reduced mortality. In recent years, the mortality of patients operated without extracorporeal circulation has decreased from 5.71% to 4% for those who underwent extracorporeal circulation. CONCLUSIONS: Nowadays, cardiac surgery in older patients accounts for more than 30% of our surgical activity. Mortality is being controlled although comorbidity is increasing. The difference with respect to younger people is due to comorbidity (creatinine > 2 mg/dl, combined surgery, and previous surgery) and the higher probability of complications (infections, renal, and respiratory complications), which worsens prognosis. We believe that off-pump coronary surgery helps to improve results.

Defects of mtDNA replication impaired mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and chagasic patients: the role of Nrf1/2 and antioxidant response.

BACKGROUND: Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)-regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. METHODS AND RESULTS: We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi-infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)-regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. CONCLUSIONS: The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi-infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease.

Cardiac-oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in chagas disease pathogenesis.

Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD(50) sensitivity to 30 µM 4-HNE and 100 µM H(2)O(2) at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H(2)O(2) resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease.

Cirugía cardíaca en el anciano / Cardiac Surgery in Elderly Patients

Objetivo. Analizamos la morbimortalidad en pacientes de más de 70 años intervenidos consecutivamente en los últimos 17 años. Pacientes y método. Estudio retrospectivo de 1.305 pacientes (654 valvulares, 531 coronarios y 120 combinados) intervenidos entre enero de 1985 y diciembre de 2001, con una edad media de 73,7 años. Observamos la progresión de la enfermedad, la comorbilidad y los resultados. En los últimos 3 años (436 enfermos), relacionamos la enfermedad prequirúrgica y la evolución. Resultados. La mortalidad media histórica fue del 16 por ciento (valvulares 18 por ciento, coronarios 11 por ciento y combinados 23 por ciento) y en los últimos 3 años del 11 por ciento (15,17, 6,26 y 16,18 por ciento, respectivamente), pese a una mayor comorbilidad. La presencia de comorbilidad y complicaciones se incrementó con la edad (p < 0,05). La estancia media en la unidad de críticos fue de 5 días, y la hospitalaria de 15,5 días. Los factores predictivos independientes de morbilidad fueron: insuficiencia renal previa, reintervención y cirugía combinada. Los factores predictivos independientes de mortalidad fueron: intervención previa, cirugía valvular y cirugía combinada frente a la coronaria, con una clara tendencia en la obesidad. La aparición de complicaciones en el postoperatorio (renal, respiratoria, infecciosa o IAM) fue un factor predictivo independiente de mortalidad. La cirugía sin circulación extracorpórea (CEC) ha supuesto una disminución de la mortalidad, siendo ésta en los últimos 2 años del 4 frente al 5,71 por ciento en pacientes coronarios con CEC. Conclusiones. La cirugía cardíaca en pacientes de edad avanzada supera el 30 por ciento de nuestra actividad, con un aumento de la comorbilidad, aunque una mortalidad decreciente. La diferencia con el paciente joven radica en la comorbilidad (insuficiencia renal previa, intervención quirúrgica previa y cirugía combinada), y la mayor facilidad para presentar complicaciones (renales, respiratorias, infecciosas) que ensombrecerán el pronóstico. La cirugía coronaria sin CEC contribuirá a una mejora en los resultados (AU)