This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (7) Citing Articles via Google Scholar Google Scholar Articles by Sato, Y. Articles by Grocott, H. P. Search for Related Content PubMed PubMed Citation Articles by Sato, Y. Articles by Grocott, H. P. Related Collections Surgery Heart Neuroanesthesia

---

CARDIOVASCULAR ANESTHESIA

Differential Cerebral Gene Expression During Cardiopulmonary Bypass in the Rat: Evidence for Apoptosis?

Yukie Sato, MD^*, Daniel T. Laskowitz, MD, Ellen R. Bennett, PhD, Mark F. Newman, MD^*, David S. Warner, MD^*, and Hilary P. Grocott, MD FRCPC^*

Departments of *Anesthesiology, Medicine (Neurology), and Pathology, Duke University Medical Center, Durham, North Carolina

Address correspondence and reprint requests to Hilary Grocott, MD, Associate Professor of Anesthesiology, Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710. Address e-mail to h.grocott{at}duke.edu

Cardiopulmonary bypass (CPB) is associated with a spectrum of cerebral injuries. The molecular changes in the brain that might contribute to these injuries are not clearly known. We sought to determine whether the expression of apoptotic genes is increased after CPB in the rat. Rats (n = 7) were subjected to 90 min of normothermic CPB. A group of sham-operated rats (n = 7) served as non-CPB controls. After a 3-h post-CPB period of recovery, their brains were removed, homogenized, and processed for messenger RNA (mRNA) extraction. By using a ribonuclease protection assay, the ratios of both pro- and antiapoptotic mRNA (bcl-x, bcl-2, bax, caspase 2, and caspase 3) to the housekeeping glyceraldehyde phosphate dehydrogenase (GAPDH) gene were determined. Additionally, Western immunoblotting was performed to detect the presence of activated caspase 3, a protein central in the apoptotic process. Compared with the non-CPB controls, the CPB group had significantly increased levels of apoptotic/GAPDH mRNA ratios (bcl-x, 0.414 ± 0.152 CPB versus 0.251 ± 0.051 non-CPB, P = 0.048; caspase 2, 0.030 ± 0.014 CPB versus 0.018 ± 0.005 non-CPB, P = 0.048; bax, 0.106 ± 0.035 CPB versus 0.066 ± 0.009 non-CPB, P = 0.009; bcl-2, 0.011 ± 0.006 CPB versus 0.006 ± 0.002 non-CPB, P = 0.035). However, no activated caspase 3 protein was detected in either group. Elucidating the molecular biological sequelae of CPB may aid in the understanding of the pathophysiology of cardiac surgery-associated cerebral injury and, in doing so, may be useful in identifying potential therapeutic targets for pharmacologic neuroprotection.

IMPLICATIONS: Cardiopulmonary bypass (CPB) appears to induce transcription of pro- and antiapoptotic genes in the rat brain, but caspase-mediated apoptosis itself does not appear to be activated. Elucidating the molecular biological sequelae of CPB may aid in the understanding of the pathophysiology of cardiac surgery-associated cerebral injury and, in doing so, may be useful in identifying potential therapeutic targets for pharmacologic neuroprotection.

This article has been cited by other articles:

				C. D. Mazer, F. Briet, K. R. Blight, D. J. Stewart, M. Robb, Z. Wang, A. M. Harrington, W. Mak, X. Li, and G. M.T. Hare Increased cerebral and renal endothelial nitric oxide synthase gene expression after cardiopulmonary bypass in the rat J. Thorac. Cardiovasc. Surg., January 1, 2007; 133(1): 13 - 20. [Abstract] [Full Text] [PDF]

				T.-J. Zhang, J. Hang, D.-X. Wen, Y.-N. Hang, and F. E. Sieber Hippocampus bcl-2 and bax expression and neuronal apoptosis after moderate hypothermic cardiopulmonary bypass in rats. Anesth. Analg., April 1, 2006; 102(4): 1018 - 1025. [Abstract] [Full Text] [PDF]

				T. Zaitseva, G. Schears, S. Schultz, J. Creed, D. Antoni, D. F. Wilson, and A. Pastuszko Circulatory Arrest and Low-Flow Cardiopulmonary Bypass Alter CREB Phosphorylation in Piglet Brain Ann. Thorac. Surg., July 1, 2005; 80(1): 245 - 250. [Abstract] [Full Text] [PDF]