A novel approach to maintaining cardiovascular stability after hemorrhagic shock: beneficial effects of adrenomedullin and its binding protein.

Abstract

BACKGROUND:

Vascular responsiveness to adrenomedullin (AM), a recently discovered vasodilator peptide, is depressed after hemorrhage and resuscitation. Downregulation of AM binding protein-1 (ie, AMBP-1) appears to be responsible for this hyporesponsiveness. Therefore, we hypothesize that administration of AM/AMBP-1 improves cardiovascular responses after hemorrhagic shock and resuscitation.

METHODS:

Male rats were bled to and maintained at a mean blood pressure of 40 mm Hg for 90 minutes. The animals were then resuscitated with 4 times the volume of shed blood with Ringer's lactate over 60 minutes. At 15 minutes after the beginning of resuscitation in hemorrhaged animals, AM alone, AMBP-1 alone, AM in combination with AMBP-1, or vehicle (phosphate-buffered saline solution) was administered intravenously over 45 minutes. At 4-hour postresuscitation, in vivo left ventricular contractility parameters, maximal rates of ventricular pressure increase (+dP/dt max ) and decrease (-dP/dt max ), were determined. Cardiac output and organ blood flow were measured with the use of radioactive microspheres. In an additional group of animals, cardiac tumor necrosis factor-alpha (TNF-alpha) levels were measured by an enzyme-linked immunosorbent assay.

RESULTS:

Four hours after resuscitation, +dP/dt max , -dP/dt max , cardiac output, and organ blood flow in the liver, small intestine, and kidneys were decreased while treatment with AM/AMBP-1 increased these parameters ( P < .05). Moreover, cardiac TNF-alpha levels were elevated at 4 hours after hemorrhage and resuscitation, while AM/AMBP-1 treatment reduced them to sham levels ( P < .05).

CONCLUSIONS:

Administration of AM/AMBP-1 appears to be a useful approach for restoring and maintaining cardiovascular stability after severe hemorrhagic shock and crystalloid resuscitation.

• Authors: Rongqian Wu, Weifeng Dong, Mian Zhou, Xiaoxuan Cui, H Hank Simms, Ping Wang
• Journal: Surgery (Surgery) Vol. 137 Issue 2 Pg. 200-8 (Feb 2005) ISSN: 0039-6060 [Print] United States
• PMID: 15674202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• CFH protein, human
• Peptides
• Tumor Necrosis Factor-alpha
• adrenomedullin-binding protein 1, human
• Adrenomedullin
• Complement Factor H

Topics

• Adrenomedullin
• Animals
• Blood Pressure (drug effects)
• Cardiac Output (drug effects)
• Complement Factor H (therapeutic use)
• Heart Rate (drug effects)
• Humans
• Male
• Myocardial Contraction (drug effects)
• Peptides (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Shock, Hemorrhagic (drug therapy, physiopathology)
• Tumor Necrosis Factor-alpha (metabolism)
• Ventricular Function, Left (drug effects)