Opioid Peptides Increase Blood Pressure and Enhance Survival of Rats Undergoing Hemorrhagic Shock Without Fluid Resuscitation
Abstract
Rats weighing 300-350 g had catheters placed in the femoral artery (for hemorrhage), tail artery for blood pressure (BP) measurements and the tail vein (for administration of opioids) controls received saline or opioids without hemorrhage. For the moderate hemorrhage studies (5.5 ml hemorrhage volume) animals received saline or Deltorphin-D (Delt-D) a delta specific opioid receptor agonist prior to hemorrhage without fluid resuscitation and post-treated animals received saline or Delt-D 1 mg/kg or Delt-D 2 mg/kg following hemorrhage without fluid resuscitation. BP, blood loss and rectal temp, at beginning and end of hemorrhage were determined. The effect of Delt-D infusions on the expression of Ubiquitin B and C (UBB and UBC) was determined. Heat Shock Protein (HSP- 70), and inducible Nitric Oxide Synthase (iNOS) mRNA transcripts in heart, leg and brain were determined after 2 hr. Preinfusions of Delt-D did not significantly effect BP while 2 mg/kg posthemorrhage infusions without resuscitation fluid significantly increased BP compared to controls and decreased core temp by 4.5 F compared to controls. Delt-D infusions increased iNOS and HSP70 mRNA in heart and leg in non-hemorrhaged controls and UBB in brain of non-hemorrhaged controls. Pre-treated Delt-D animals had elevated brain iNOS and HSP70 mRNA, and posthemorrhage Delt-D treated animals had elevated UBC mRNA in heart and brain and HSP70 mRNA in leg tissue. For the severe hemorrhage protocol (9.0 - 11.0 ml hemorrhage volume representing 53-61% of total blood volume), rats were infused with either 3.0 mg/kg of a highly specific mu opioid, (ZGI-06) or a Delt-D variant (ZGI-07) and ischemic tolerance (ie BP and 6 hr survival) was monitored. Controls were infused with 1.0 ml PBS.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA444689
Entities
People
- Meera Govindaswami
- Peter R. Oeltgen
Organizations
- University of Kentucky