B. Murzi

C. Caselli

CLERICO, ALDO

D. Giannessi

M. Cabiati

M. Cantinotti

S. Del Ry

S. Storti

T. Prescimone

Archivio della ricerca della Scuola Superiore Sant'Anna

Clinical Biochemistry 45 (2012) 1510–1512Contents lists available at SciVerse ScienceDirectClinical Biochemistryj ourna l homepage: www.e lsev ie r .com/ locate /c l inb iochemCase ReportAdiponectin plasma levels decrease after surgery in pediatric patients withcongenital heart diseaseChiara Caselli a, Massimiliano Cantinotti b, Silvia Del Ry a, Manuela Cabiati a, Tommaso Prescimone a,Simona Storti b, Bruno Murzi b, Aldo Clerico b, Daniela Giannessi a,⁎a Consiglio Nazionale delle Ricerche (CNR), Institute of Clinical Physiology, Laboratory of Cardiovascular Biochemistry, Pisa, Italyb Fondazione CNR-Regione Toscana “G. Monasterio”, Pisa and Massa, Italy⁎ Corresponding author at: CNR Institute of Clinical Pdiovascular Biochemistry, Pisa Research Area, Via G.Fax: +39 050 3152166.E-mail address: danielag@ifc.cnr.it (D. Giannessi).0009-9120/$ – see front matter © 2012 The Canadian Sdoi:10.1016/j.clinbiochem.2012.07.096a b s t r a c ta r t i c l e i n f oArticle history:Received 27 April 2012Accepted 12 July 2012Available online 22 July 2012Keywords:AdiponectinPediatric patientsInﬂammationMetabolismCongenital heart diseaseObjective: Adiponectin is a protein secreted by adipose tissue and involved in inﬂammatory process aswell as in metabolic regulation. The aim of this study was to examine the response of plasma adiponectinto cardiac surgery in children with congenital defects to determine whether its measurement is associatedto the response to injury.Design and methods: Twenty-ﬁve pediatric patients undergoing heart surgery for correction of congen-ital defects were studied. Adiponectin plasma levels, obtained pre- and three times postoperatively, were de-termined by dedicated ELISA. Brain natriuretic peptide (BNP) plasma levels were also determined.Results: Adiponectin levels are highest in the ﬁrst month of life (p=0.004 newborns vs. children) with aprogressive fall in the next few years. After surgery, adiponectin increased slowly over a 1-month period, fol-lowing an initial decrease in the ﬁrst 3 days.Conclusions: Adiponectin could be involved in the acute response to injury although further investiga-tion into the relationship between adiponectin, glucose regulation and inﬂammatory process is necessaryto examine the issue of the adiponectin decrease after surgery from a more integrated prospective.© 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.IntroductionMetabolic responses to surgical injury are partly regulated by twoprocesses, the acute phase and the glycemic response. During the ﬁrstphase, Interleukin (IL)-6 stimulates the liver to produce proteins,such as C-reactive protein (CRP), proportionally to the dimension ofthe injury and typically reaching a peak within 72 h [1]. Soon after,the glycemic response occurs, resulting in hyperglycemia propor-tional to the extent of the injury [2]. Regarding cardiac surgery,in pediatric patients cardiopulmonary by-pass induces a systemicinﬂammatory response, involving CRP [1,2] and IL-6 [3] and causesperi-operative hyperglycemia [4]. In neonates, hormonal and meta-bolic responses are distinct and more extreme than in adult patientsand are associated with a high hospital mortality rate [1].At the present, few data are available on interrelationship betweeninﬂammatory (acute phase) and glycemic metabolic injury-responseparameters in association with injury severity and outcome in the pedi-atric cardiosurgery setting. Adiponectin, an adipocyte-derived protein,exerts anti-inﬂammatory and insulin-sensitizing actions [5]. In childhood,hysiology, Laboratory of Car-Moruzzi, 1 56100 Pisa, Italy.ociety of Clinical Chemists. Publishethe use of adiponectin as a biomarker for insulin sensitivity and/or as arisk factor for cardiovascular disease is gaining support [6].The aim of this preliminary studywas to check if plasma adiponectinis modulated by cardiac surgery in order to explore the possibility touse this protein as biomarker of the post-surgery response. For this,adiponectin levels were measured in pediatric patients before andafter cardiac surgery performed to correct congenital defects up to 1month, a time largely higher of the post-cardiac recovery. Few dataare available on this issue [7], especially in children, so these resultswill be a starting point to plan a larger study devoted to investigatethe role of adiponectin in the inﬂammatory/metabolic response aftercardiosurgery in pediatric patients. Due to the relationship of natriureticpeptide on adiponectin production [8], plasma levels of brain natriureticpeptide (BNP) were also determined in the same patients at baseline.Material and methodsWe studied a group of 25 neonates and infants admitted to the Pedi-atric Cardiac Surgery Unit of Heart Hospital, Fondazione Monasterio,Massa, Italy (14 males, 64±72 months, mean±SD) with various cardi-ac defects (2 aortic coarctation, 4 atrial septal defects, 1 congenitalcorrected transposition, 2 cardiomyopathies, 2 total anomalous pulmo-nary venous return, 3 transposition of the great arteries, 3 tetralogy ofFallot, 4 univentricular heart, and 4 ventricular septal defects).d by Elsevier Inc. All rights reserved.Fig. 2. Relationship between adiponectin and BNP at baseline: the values of the plasmalevels after natural logarithmic transformation are reported (Spearman's rho=0.628,p=0.002).1511C. Caselli et al. / Clinical Biochemistry 45 (2012) 1510–1512Children were evaluated before surgery by physical examination,standard 12-lead electrocardiogram, and chest X-ray. Diagnosis ofcongenital heart disease (CHD) was made by means of a standardtrans-thoracic echocardiography according to international guide-lines [9]. In the postoperative period, medical hemodynamic man-agement involved epinephrine (0.005–0.15 μg/kg/min), milrinone(0.5–0.75 μg kg/min), dopamine (5–20 μg /kg/min), and noradrena-line (0.05–0.5 μg/kg/min). Diuretic management usually involvedfurosemide (1 – 10 mg/kg/day). From all patients a blood sample wascollected on the day of clinical ward admission (basal conditions). Thetime-course of adiponectin in the ﬁrst month after surgery wasdetermined in a sub-group of 21 children (45±62 months, mean±SD,13 males) undergone correction/pallation of CHD. Blood was collectedat different times after surgery for routinary clinical evaluation.Informed consent was given by all parents of newborns and infantsenrolled in this study and the protocol was approved by the local ethicscommittee.Plasma adiponectin was measured by a dedicated ELISA (Linco Re-search, St. Charles, MO, USA) previously described in detail [10]; plasmaBNP was determined using the fully automated Access platform (AccessImmunoassay Systems; Beckman Coulter, Inc., Fullerton, CA, USA).Standard statistical analysis was carried out using the SPSS 16.0for Mac (1989–2007, SPSS Inc., Chicago, IL, USA). Because adiponectinlevels are not normally distributed, the original data were analyzedusing non-parametric tests. A 2-tailed P-valueb0.05 was consideredstatistically signiﬁcant.ResultsAdiponectin values of CHD patients, divided according to age, arereported in Fig. 1. Adiponectin levels are highest in the ﬁrst monthof life (p=0.004 newborns vs. children) with a progressive fall inthe next few years, as previously found by us in healthy children(11). At baseline, BNP plasma levels in CHD children were 1328±535pg/mL and showed a signiﬁcant relationshipwith circulating adiponectin(Spearman's rho=0.628, p=0.002) (Fig. 2), as observed in healthychildren (11).The time-course of adiponectin levels in CHD patients after sur-gery is shown in Fig. 3. After an initial decrease in the ﬁrst 3 daysafter surgery, adiponectin levels increased slowly during the follow-ing 2 weeks, reaching a plateau value in 1 month (Fig. 3A). To avoidbiological differences that could affect the pattern of the time course01 1 12month year yearsp = 0.004102030Adiponectin, µg/mL405060Fig. 1. Adiponectin plasma levels in CHD patients divided according to age:≤1 month (n=8, 6 males); ≤1 year (n=5, 2 males); ≤12 years (n=12, 6 males). Foreach group, median values, 5th, 25th, 75th and 95th percentiles are reported. No signiﬁ-cant differences were found between the ≤1 year group and both ≤1 month and≤12 years groups.after surgery, probably masking the true effects, the percent varia-tion of adiponectin with respect to baseline as a function of thepost-surgery time has been also reported (Fig. 3B). The similar be-havior of both the absolute and percent variations of adiponectin inthe post-surgery suggests that the adiponectin response to injury issimilar irrespective of biological differences such as the etiology ofthe congenital defects.DiscussionThe results from this preliminary study indicate that adiponectin sig-niﬁcantly decreases in the ﬁrst 3 days after surgery, with a progressivesigniﬁcant increase over the next 2 weeks (Fig. 3). This behavior,Fig. 3. Time course of adiponectin plasma levels up to 1 month after surgery: A. meanvalues (±SEM) of adiponectin concentrations; B. percentage of change after surgery. Nosigniﬁcant differences were found between adiponectin values at baseline and 1, 2 and4 weeks, respectively.1512 C. Caselli et al. / Clinical Biochemistry 45 (2012) 1510–1512although observed in a small number of patients, suggests the involve-ment of adiponectin in themetabolic response to injury. The fall of circu-lating adiponectin levels observed at 3 days coincides with the acutephase, characterized by high levels of inﬂammatory markers within72 h [1]. Thus, the up-regulation of inﬂammatory cytokines could con-tribute to the decline of adiponectin levels through a decrease in its rateof synthesis in adipose tissue. The glycemic response is concomitantwith this process and the lower adiponectin levels could play a part inpromoting hyperglycemia. Adiponectin levels fall in obese and diabeticindividuals as well as in subjects with coronary heart disease, due toinhibition by the inﬂammatory process, suggesting that the loweringof adiponectin levels may contribute to metabolic abnormalities [5].Thus, in our setting the adiponectin could be a possible link betweenthe acute and glycemic phases of the metabolic response.On the other hand, our data closely agree with the observationthat plasma adiponectin declines transiently following myocardialischemia–reperfusion injury [12,13]. Adiponectin accumulates in theheart following injury largely as a result of leakage from the vascularcompartment, contributing to the decline of circulating adiponectinlevels. Furthermore, in damaged myocardial tissue, adiponectin partic-ipates in the wound healing process by binding the extra-cellular ma-trix, and explicates its cardioprotective properties against myocardialreperfusion injury by the inhibition of remodeling and apoptosis in car-diacmyocytes and ﬁbroblasts exposed to hypoxia-reoxygenation stress[12].At baseline, adiponectin levels are highest in the ﬁrst month of life,with a progressive fall in the following months and years in CHD sub-jects (Fig. 1), as previously found in healthy control subjects [11]. Thisdecrease as a function of the age could be associated with differencesbetween neonates, infants, and children in fat distribution, adipocytesize, inﬂammation and diet [14]. Moreover, the correlation betweenadiponectin and BNP at baseline suggests that BNP could contributeto the adiponectin levels in CHD patients, conﬁrming the relation ob-served in healthy pediatric population [11].ConclusionsOur data strongly suggest that plasma adiponectin is modiﬁed inresponse to cardiac surgery. This observation, which merits furtheranalysis, in turn indicates that adiponectin evaluation may be usefulto better assess the immediate metabolic response to injury, a criticalissue in pediatric patients and in particular in newborns, inwhichdeter-mination of adiponectin levels could also be important in addressingnutritional support in the postoperative period [15].References[1] Brunengraber LN, Robinson AV, Chwals WJ. Relationship of serum C-reactive pro-tein and blood glucose levels with injury severity and patient morbidity in apediatric trauma population. J Pediatr Surg 2009;44:992-6.[2] Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, Nadkarni V. Associationof timing, duration, and intensity of hyperglycemia with intensive care unit mor-tality in critically ill children. Pediatr Crit Care Med 2004;5:329-36.[3] Gupta M, Johann-Liang R, Sison CP, Quaegebeur J, Friedman DM. Relation of earlypleural effusion after pediatric open heart surgery to cardiopulmonary bypass timeand systemic inﬂammation as measured by serum interleukin-6. Am J Cardiol2001;87:1220-3.[4] Moga MA, Manlhiot C, Marwali EM, McCrindle BW, Van Arsdell GS, Schwartz SM.Hyperglycemia after pediatric cardiac surgery: impact of age and residual lesions.Crit Care Med 2011;39:266-72.[5] Ouchi N, Walsh K. Adiponectin as an anti-inﬂammatory factor. Clin Chem Acta2007;380:24-30.[6] Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, et al. Progressand challenges inmetabolic syndrome in children and adolescents: a scientiﬁc state-ment from the American Heart Association Atherosclerosis, Hypertension, andObesity in the Young Committee of the Council on Cardiovascular Disease inthe Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physi-cal Activity, and Metabolism. Circulation 2009;119:628-47.[7] Takenaka K, Ogawa E, Wada H, Hirata T. Systemic inﬂammatory response syn-drome and surgical stress in thoracic surgery. J Crit Care 2006;21:48-53 discus-sion 53–55.[8] Tsukamoto O, FujitaM, KatoM, Yamazaki S, AsanoY, Ogai A, et al. Natriuretic peptidesenhance the production of adiponectin in human adipocytes and in patients withchronic heart failure. J Am Coll Cardiol 2009;53:2070-7.[9] Cantinotti M, Passino C, Storti S, Ripoli A, Zyw L, Clerico A. Clinical relevance oftime course of BNP levels in neonates with congenital heart diseases. Clin ChimActa 2011;412:2300-4.[10] Caselli C, Melaiu O, Maltinti M, Del Ry S, Cabiati M, Prescimone T, et al. A method-ological reappraisal of total and high molecular weight adiponectin determina-tion in human peripheral circulation: comparison of four immunometric assays.Clin Chem Lab Med 2010;48:561-8.[11] Caselli C, Cantinotti M, Del Ry S, Cabiati M, Prescimone T, Storti S, et al. Relationbetween adiponectin and brain natriuretic peptide in healthy pediatricsubjects: from birth through childhood. Nutr Met Cardiovasc Dis 2012, http://dx.doi.org/10.1016/j.numecd.2012.03.004 [Jun 28, Electronic publication aheadof print].[12] Shibata R, Sato K, Kumada M, Izumiya Y, Sonoda M, Kihara S, et al. Adiponectinaccumulates in myocardial tissue that has been damaged by ischemia–reperfusioninjury via leakage from the vascular compartment. Cardiovasc Res 2007;74:471-9.[13] Kojima S, Funahashi T, Sakamoto T, Miyamoto S, Soejima H, Hokamaki J, et al. Thevariationof plasma concentrations of a novel, adipocyte derivedprotein, adiponectin, inpatients with acute myocardial infarction. Heart 2003;89:667.[14] Savino F, Petrucci E, Nanni G. Adiponectin: an intriguing hormone for paediatri-cians. Acta Paediatr 2008;97:701-5.[15] Owens JL, Musa N. Nutrition support after neonatal cardiac surgery. Nutr ClinPract 2009;24:242-9.

Adiponectin plasma levels decrease after surgery in pediatric patients with congenital heart disease

Adiponectin plasma levels decrease after surgery in pediatric patients with congenital heart disease

Abstract

Similar works

Full text

Available Versions

Archivio della ricerca della Scuola Superiore Sant'Anna