A thorough understanding of the physiological consequences of traumatic blood loss is essential to effective medical management of the problem and the associated complications. The response to blood loss in conscious animals (including humans) is biphasic. The pattern is characterized initially by sympathoexcitation and arterial blood pressure maintenance with little activation of humoral systems. This is followed later by sympathoinhibition, vasodilation, hypotension, and increased release of vasopressin, epinephrine and renin. Very little is actually known about the central nervous system networks controlling the onset of hypotension. The periaqueductal gray (PAG) is a brain area that may be important in the control of the cardiovascular and neurohumoral response to blood loss. Our general hypothesis is that the ventrolateral PAG is important in the central control of the integrated hemodynamic and neurohumoral response to hemorrhage and stressful sensory stimuli. We will use a combination of approaches to evaluate ventrolateral PAG involvement in cardiovascular control during acute hypotensive hemorrhage in conscious rabbits. The use of this combination of approaches is novel, and this will be one of the first studies to address ongoing central cardiovascular control mechanisms during a physiological event such as hemorrhage.
The Specific Aims of this study are: 1) To define the role of the ventrolateral PAG in the hemodynamic response to blood loss and stress in the conscious rabbit. 2) To quantify the response of ventrolateral PAG neurons during hemorrhage and stress in the conscious rabbit. 3) To understand the role of serotonergic and opioidergic mechanisms in the ventrolateral PAG during blood loss in the conscious rabbit.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL063910-04
Application #
6751602
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Sopko, George
Project Start
2001-06-15
Project End
2006-05-31
Budget Start
2004-06-01
Budget End
2006-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$253,750
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Organized Research Units
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211
Strittmatter, Rachel R; Schadt, James C (2007) Sex differences in the respiratory response to hemorrhage in the conscious, New Zealand white rabbit. Am J Physiol Regul Integr Comp Physiol 292:R1963-9
McKown, Michael D; Schadt, James C (2006) A modification of the Harper-McGinty microdrive for use in chronically prepared rabbits. J Neurosci Methods 153:239-42
Schadt, James C; Shafford, Heidi L; McKown, Michael D (2006) Neuronal activity within the ventrolateral periaqueductal gray during simulated hemorrhage in conscious rabbits. Am J Physiol Regul Integr Comp Physiol 290:R715-25