title: Relation of Cytokine Profile to Clinical and Hemodynamic Features in Young Patients With Congenital Heart Disease and Pulmonary Hypertension.
abstract: In congenital heart disease, severity of pulmonary hypertension and operability is defined by noninvasive parameters (clinical history, physical examination, and echocardiography) and sometimes, cardiac catheterization. We investigated how circulating levels of inflammatory mediators correlate with such parameters in a young pediatric population (age, 2.0 months to 3.1 years) and the effects of preoperative pulmonary vasodilator therapy with sildenafil. Cytokines were analyzed in serum using chemiluminescence signals. In the whole patient group (n = 47), interleukin 17E, a Th2 immune response mediator increased with increasing age, considered as a parameter of disease severity (R2= 0.24, p <0.001), whereas the angiogenic chemokine growth-regulated oncogene alpha decreased (R2= 0.21, p = 0.001). Macrophage migration inhibitory factor chemokine was greater in subjects with elevated pulmonary vascular resistance (n = 16, p = 0.022), whereas regulated on activation, normal T cell expressed and secreted chemokine was greater in subjects with pulmonary congestion due to increased pulmonary blood flow (n = 31, p = 0.037). The observations were the same for the specific subpopulation of patients with Down syndrome (p = 0.009 and p = 0.012 for migration inhibitory factor and regulated on activation, normal T cell expressed and secreted in the respective subgroups). Sildenafil administration to patients with elevated pulmonary vascular resistance resulted in improvement of pulmonary blood flow (p = 0.012) and systemic oxygen saturation (p = 0.010), with a decrease in serum interleukin 6 (p = 0.027) and soluble ICAM-1 (p = 0.011). In conclusion, levels of circulating inflammatory molecules seem to correlate with disease severity in this population, with potential pathophysiological and therapeutic implications.
authors.affiliation: Department of Pediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Leína
authors.initials: L
authors.lastname: Zorzanelli
authors.affiliation: Pró-Sangue Foundation, São Paulo, Brazil.
authors.forename: Nair
authors.initials: N
authors.lastname: Maeda
authors.affiliation: Department of Pediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Clavé
authors.affiliation: Department of Pediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Ana
authors.initials: A
authors.lastname: Thomaz
authors.affiliation: Department of Anesthesiology, Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Filomena
authors.initials: F
authors.lastname: Galas
authors.affiliation: Stanford University School of Medicine, Stanford, California.
authors.forename: Marlene
authors.initials: M
authors.lastname: Rabinovitch
authors.affiliation: Department of Pediatric Cardiology and Adult Congenital Heart Disease, Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil. Electronic address: aablopes@usp.br.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopes
mesh_terms: D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood* / Q000503:physiopathology* / Q000601:surgery; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000503:physiopathology* / Q000601:surgery; D007223:Infant; D008297:Male; D000068677:Sildenafil Citrate / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
chemical_list: D016207:Cytokines; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate