Hemmorhagic Shock: Effects of Dopamine on the Diaphragm

Fluid resuscitation strategies for the military are based on the principles of the Advanced Trauma Support Life (ATLS) course. Thus, military personnel treat hemorrhagic shock in the field and hospitals with fluid resuscitation using Lactated Ringer's (LR) and Hespan. The objective of these fluids is to normalize hemodynamic parameters 3,4 Aubier 5 suggested respiratory failure and severe hypoxemia occur during hemorrhagic shock before circulatory collapse. There are no published studies investigating dopamine and diaphragm function following hemorrhagic shock. Using an in-vivo rat model, we obtained pilot data indicating diaphragmatic function is decreased following hemorrhagic shock. Infusion of dopamine improved diaphragm performance and reduced diaphragm cells from undergoing apoptosis. These effects of dopamine may be a result of dopamine increasing diaphragm blood flow, dopamine binding to beta-2 adrenoceptors and/or dopamine scavenging free radicals. The latter two effects attenuate apoptosis. The goal of this project is to delineate the physiologic and molecular changes in the diaphragm following hemorrhagic shock and the effects of different fluid resuscitation strategies, particularly dopamine.

tAnesthetized adult male rats will be bled via the carotid artery to produce a mean arterial blood pressure of approximately 70 mm Hg which will be maintained for 60 minutes. Fluid resuscitation will then be initiated after 60 minutes using each of the following: LR, Hextend, blood (autotransfusion) or dopamine (10 ┬╡g/kg/min) with LR or Hextend or blood. Throughout the experiment, diaphragm shortening, blood pressure, heart rate, and respiratory rate will be recorded. In addition, fluorescent microspheres will be injected for measurement of cardiac output and diaphragm blood flow. Blood samples will be obtained for arterial blood gas analysis. At the end of each treatment, the diaphragm will be removed and processed for fluorescent microspheres and apoptosis. This study will advance our understanding of hemorrhagic shock and the effects of dopamine on diaphragm function.

Final report is available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2011108215.xhtml