Laparoscopic surgery represents a new paradigm, with less pain, quicker recovery times, and reduced disability. In time, most general surgical procedures will be performed in this manner. Laparoscopic surgery is not simply a reduced surgical insult, it is a different surgical insult. Preliminary data in the rat shows that a pneumoperitoneum with CO2 gas alters the inflammatory response associated with laparoscopic surgery in the setting of sepsis. The objective of this application is to establish whether CO2 pneumoperitoneum has a modifying role, and to determine the possible mechanism(s).
AIM 1 : To test whether CO2 modifies the inflammatory response during laparoscopic surgery. The effect of pneumoperitoneum with CO2, helium, or air on the inflammatory response after sepsis (cecal ligation and puncture) will be compared. The parameters of the inflammatory response to be evaluated are: leukocytosis, leukocyte infiltration, hepatic acute phase gene expression, and circulating levels of cytokines.
AIM 2 : To determine where in the pathway of the inflammatory response CO2 pneumoperitoneum exerts its effect. Expression of the acute phase proteins will be used as an experimental paradigm. Pre-transcriptional, transcriptional, and post transcriptional regulation of the acute phase genes will be evaluated.
AIM 3 : To determine how the C02 pneumoperitoneum alters the inflammatory response. The hypothesis of this aim is that alteration of pH with abdominal distension alters the inflammatory response. A) Arterial pH will be measured to correlate pH changes with immune modulation. B) The pH will be artificially decreased by a comparable amount via systemic intravenous infusion of hydrochloric acid in the setting of sepsis plus C02 pneumoperitoneum, helium pneumoperitoneum, air pneumoperitoneum, and open surgery. The information provided by this investigation will be essential in patient care as increasing numbers of patients undergo operations using the CO2 pneumoperitoneum.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM062899-03
Application #
6767630
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
Project Start
2002-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
3
Fiscal Year
2004
Total Cost
$294,300
Indirect Cost
Name
Johns Hopkins University
Department
Surgery
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Fuentes, J M; Fulton, W B; Nino, D et al. (2008) Atropine treatment modifies LPS-induced inflammatory response and increases survival. Inflamm Res 57:111-7
Grabowski, Julia E; Vega, Virginia L; Talamini, Mark A et al. (2008) Acidification enhances peritoneal macrophage phagocytic activity. J Surg Res 147:206-11
Hanly, Eric J; Aurora, Alexander A; Shih, Samuel P et al. (2007) Peritoneal acidosis mediates immunoprotection in laparoscopic surgery. Surgery 142:357-64
Fuentes, Joseph M; Hanly, Eric J; Aurora, Alexander R et al. (2006) CO2 abdominal insufflation pretreatment increases survival after a lipopolysaccharide-contaminated laparotomy. J Gastrointest Surg 10:32-8
Hanly, E J; Fuentes, J M; Aurora, A R et al. (2006) Carbon dioxide pneumoperitoneum prevents mortality from sepsis. Surg Endosc 20:1482-7
Fuentes, J M; Hanly, E J; Aurora, A R et al. (2006) Laparoscopic surgery and the parasympathetic nervous system. Surg Endosc 20:1225-32
Fuentes, Joseph M; Talamini, Mark A; Fulton, William B et al. (2006) General anesthesia delays the inflammatory response and increases survival for mice with endotoxic shock. Clin Vaccine Immunol 13:281-8
Hanly, Eric J; Bachman, Sharon L; Marohn, Michael R et al. (2005) Carbon dioxide pneumoperitoneum-mediated attenuation of the inflammatory response is independent of systemic acidosis. Surgery 137:559-66
Fuentes, Joseph M; Hanly, Eric J; Aurora, Alexander R et al. (2005) Anesthesia-specific protection from endotoxic shock is not mediated through the vagus nerve. Surgery 138:766-71
Fuentes, Joseph M; Hanly, Eric J; Bachman, Sharon L et al. (2004) Videoendoscopic endotracheal intubation in the rat: a comprehensive rodent model of laparoscopic surgery. J Surg Res 122:240-8