Chronic hypoxemia increases myocardial cytochrome oxidase

ObjectiveCyanotic patients have potentially decreased tissue oxygen tension. Cytochrome oxidase catalyzes the reduction of oxygen and is integral to adenosine triphosphate production. Cytochrome oxidase subunit I, the active site, is encoded by mitochondrial DNA. Using a newborn swine model of chronic hypoxemia, we evaluated ventricular cytochrome oxidase subunit I mRNA and protein expression and assessed cytochrome oxidase activity.MethodsThirty-two newborn piglets underwent thoracotomy and placement of a pulmonary artery–to–left atrium shunt or sham operation. Two weeks later, partial pressure of arterial oxygen, hematocrit, and left ventricular shortening fraction values were compared with baseline values. Northern blot hybridization and protein immunoblotting for ventricular cytochrome oxidase subunit I were performed. Cytochrome oxidase kinetic activity was measured. Heme a,a3 content and turnover number were determined. Significance was assessed with a t test.ResultsBaseline partial pressure of arterial oxygen and hematocrit values were similar. Hypoxemic piglets had a lower partial pressure of arterial oxygen of 38 ± 10 mm Hg (P < .001) and higher hematocrit value of 31.4% ± 2.9% (P < .001) compared with a partial pressure of arterial oxygen of 140 ± 47 mm Hg and hematocrit value of 24.6% ± 3.9% after the sham operation. Baseline and postprocedure left ventricular shortening fraction were similar within and between groups. Chronic hypoxemia increased right ventricular and left ventricular cytochrome oxidase I mRNA and protein by more than 1.4-fold. Cytochrome oxidase activity increased significantly in hypoxemia by 2.5-fold compared with that seen after the sham operation. Heme a,a3 content and turnover number increased by 1.5-fold during hypoxemia.ConclusionsChronic hypoxemia increases cytochrome oxidase I message, protein expression, and activity. The increase in kinetics was due to increased enzyme content and catalytic activity. This is a possible adaptive mechanism that might preserve organ function during chronic hypoxemia

Noncoronary Cardiac Abnormalities Are Associated With Coronary Artery Dilation and With Laboratory Inflammatory Markers in Acute Kawasaki Disease

ObjectivesWe explored the association of noncoronary cardiac abnormalities with coronary artery dilation and with laboratory inflammatory markers early after Kawasaki disease (KD) diagnosis.BackgroundLeft ventricular (LV) dysfunction, mitral regurgitation (MR), and aortic root dilation occur early after diagnosis; their associations with coronary artery dilation and inflammatory markers have not been well-described.MethodsCentrally interpreted echocardiograms were obtained at KD diagnosis and 1 and 5 weeks after diagnosis on 198 subjects in the National Institutes of Health-sponsored Pediatric Heart Network KD pulsed steroid trial. Regression models were constructed to investigate the relationships among early LV dysfunction, MR, and aortic root dilation with coronary artery dilation and laboratory inflammatory markers.ResultsAt diagnosis, LV systolic dysfunction was present in 20% of subjects and was associated with coronary artery dilation, seen in 29% (p = 0.004). Although LV dysfunction improved rapidly, LV dysfunction at diagnosis predicted greater odds of coronary artery dilation at 1 and 5 weeks after diagnosis (5-week odds ratio: 2.7, 95% confidence interval: 1.2 to 6.3). At diagnosis, MR was present in 27% of subjects and aortic root dilation was present in 8%; each was associated with larger coronary artery size at diagnosis. Left ventricular dysfunction was associated with higher erythrocyte sedimentation rate and, at diagnosis only, lower serum albumin; MR was associated with higher erythrocyte sedimentation rate and lower albumin at all times. Aortic root size had little association with inflammatory markers.ConclusionsNoncoronary cardiac abnormalities are associated with coronary artery dilation and laboratory evidence of inflammation in the first 5 weeks after KD, suggesting a shared inflammatory mechanism. (Trial of Pulse Steroid Therapy in Kawasaki Disease [A Trial Conducted by the Pediatric Heart Network]; NCT00132080

Hypoplastic Left Heart Syndrome Current Considerations and Expectations

In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients

Clinical practice: the effect of obesity in children with congenital heart disease

Childhood obesity has reached epidemic proportions in many parts of the world. This epidemic has also affected children and adults with congenital heart disease (CHD). Over one quarter of children with CHD are overweight or obese. Important comorbidities are associated with obesity including type 2 diabetes, systemic hypertension, hyperlipidemia, and obstructive sleep apnea. Obese children with CHD often have the traditional risk factors such as genetic predisposition, sedentary lifestyle, and poor dietary habits. However, they may also have unique risk factors such as higher caloric needs in early infancy and exercise restriction in childhood. Similar to children with normal hearts, those with CHD have higher left ventricular mass and abnormal vascular function and are more likely to have systemic hypertension. In the long term, these comorbidities may have a more profound effect on children who have underlying functional and/or anatomical abnormalities of the heart. As more children with CHD are now surviving into adulthood, investigating therapeutic interventions to treat and prevent obesity in this population is of utmost importance. Recommendations for safe physical activity, recreation sport, and exercise training for children with CHD have recently been published. These guidelines may help health care providers to change their practice of exercise restriction

Inicio de enfermedades cardiovasculares del adulto durante la etapa fetal y la ni\uf1ez

El inicio de enfermedad cardiovascular de adulto durante la ni\uf1ez se ha convertido en un importante problema de salud p\ufablica. A\ufan se desconoce si las influencias gen\ue9ticas, ambientales o fetales son las causas primarias de la epidemia de enfermedad cardiovascular que se observa en la actualidad. Los beneficios de un estilo de vida con actividad f\uedsica general, que incluye control de peso, presi\uf3n arterial m\ue1s baja, evitaci\uf3n del consumo de tabaco, y pr\ue1ctica constante de ejercicio, son claros, y pueden tener impacto sobre la salud general de ni\uf1os y adolescentes. Los m\ue9dicos que atienden a ni\uf1os y adolescentes deben empezar a incorporar en su pr\ue1ctica pruebas para detectar trastornos cardiovasculares que persistir\ue1n hasta la adultez. La mejor comprensi\uf3n de la causa de estos estados morbosos traer\ue1 consigo terapias preventivas y dirigidas mejoradas