**7. References**


intraoperative myocardial ischemia-reperfusion in cardiac surgery. J Thorac Cardiovasc Surg *134*, 74-81, 81 e71-72.


196 Front Lines of Thoracic Surgery

exhibiting differential expression suggested that the elicited transcriptional response in this context is compensatory and adaptive. In silico functional clustering of several genes comprising this response revealed dominant up-regulation of transcripts encoding elements of pro-hypertrophic cellular growth factor pathways, involving multiple levels of regulation, including receptors, cognate signaling kinases, and programmatically linked transcription factors. The majority of genes up-regulated in response to cardioplegic arrest have literature-confirmed cytoprotective properties, including several that have been previously validated as endogenous mediators of ischemic preconditioning. This study provided evidence that myocardial ischemic stress associated with repair of VSD induces a net protective transcriptional response (Arab et al., 2007). It showed that reversible myocardial ischemia-reperfusion during cardiac surgery is associated with an immediate

genomic response that predicts a net cardioprotective phenotype (Arab et al., 2007).

**5. Conclusion** 

health care costs.

**7. References** 

**6. Acknowledgement** 

*96*, 6745-6750.

The molecular signatures identified with microarray technology can be interpreted as either mechanistically relevant to the congenital heart disease pathogenesis or as markers of disease progression. We believe that this approach can also be used to identify endogenous patterns of gene profiles that are activated in response to the primary disease-causing pathway and have the effect of generating a counteracting and highly adaptive pattern of gene activation, which serves to suppress aberrant disease-related molecular pathways.

Overall the information collected by gene expression profiling will help our understanding of disease mechanisms and provide insights useful for improving contemporary clinical

Congenital heart disease genomic research is still in its early stages with regard to the translation of studies' findings into clinical settings. However, inspection of other medical areas shows the potential of genomic medicine and where congenital heart medicine will be, possibly within the next few years. Microarrays are already being used in other fields to help clinicians better risk-stratify patients in addition to predict therapeutic responses and direct clinical and surgical decision making. Although considerable challenges remain, congenital heart disease genomic medicine promises to improve patient care and lower

We are grateful to the Bristol NIHR BRU in Cardiovascular Medicine, The Garfield Weston

Alon, U., Barkai, N., Notterman, D.A., Gish, K., Ybarra, S., Mack, D., and Levine, A.J. (1999).

Arab, S., Konstantinov, I.E., Boscarino, C., Cukerman, E., Mori, A., Li, J., Liu, P.P.,

Broad patterns of gene expression revealed by clustering analysis of tumor and normal colon tissues probed by oligonucleotide arrays. Proc Natl Acad Sci U S A

Redington, A.N., and Coles, J.G. (2007). Early gene expression profiles during

treatment and prognosis of patients with congenital heart defects.

Trust and the British Heart Foundation for their support.


**11** 

*USA* 

**B-Type Natriuretic Peptide (BNP) in** 

*1University of California San Francisco, Pediatrics, Critical Care Medicine, 2Cardiovascular Research Institute, University of California San Francisco, 3Department of Pediatrics,University of California, Davis, Pediatrics,* 

In 1988 Sudoh and colleagues described a novel natriuretic peptide in porcine brain -- brain natriuretic peptide(Sudoh et al. 1988). In fact, the peptide is most abundant in the heart and thus it is now commonly termed B-type natriuretic peptide (BNP). Myocyte pressure and/or stretch results in the release of BNP, and BNP levels are easily quantified by several commercially available assays. Data from numerous studies have now firmly established a role for BNP as a biomarker for diagnosis, prognostication, and management of adults with cardiac disease, including those undergoing cardiac surgery(Silver et al. 2004; Mitchell and Webb 2011; Rodseth, Padayachee, and Biccard 2008; Fellahi et al. 2011). Unfortunately, far fewer data are available on the role of BNP in the management of neonates, infants, and children who require cardiac surgery. This chapter will provide a brief review of these data in order to understand the potential utility of BNP determinations in this population.

Beginning with the observation by de Bold and colleagues that rats infused with atrial tissue extracts developed natriuresis and diuresis, much has been learned over the past three decades about the role of the natriuretic hormone system in the homeostatic control of fluid balance and vascular tone(de Bold et al. 1981). The natriuretic hormone system comprises several related peptides that activate specific receptors, particularly in the kidneys, myocardium, and vasculature, which use cyclic guanosine 3',5'-monophosphate (cGMP) as a second messenger(Levin, Gardner, and Samson 1998). These peptides include atrial natriuretic peptide (ANP), BNP, C-type natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP), kaliuretic peptide, and urodilantin. The primary stimulus for their release is an increase in intravascular or cardiac volume, that causes increased atrial stretch, ventricular wall stress, vascular shear stress, intravascular volume, and/or intravascular sodium concentration(Levin, Gardner, and Samson 1998). The precise roles of individual natriuretic peptides depend upon their distribution and abundance within the cardiovascular system, as

well as the specific stimulus for their release(Levin, Gardner, and Samson 1998).

**1. Introduction** 

**2. Natriuretic hormone system** 

**Neonates, Infants and Children** 

**Undergoing Cardiac Surgery** 

Sanjeev A. Datar1 and Jeffrey R. Fineman1,2

Peter E. Oishi1,2, Aida Field-Ridley3,

*Critical Care Medicine,* 

