Ghrelin maintains the cardiovascular stability in severe sepsis.

Abstract

BACKGROUND:

Cardiovascular dysfunction, characterized by reduced cardiac contractility and depressed endothelium-dependent vascular relaxation, is common in severe sepsis. Although it is known that ghrelin produces beneficial effects following various adverse circulatory conditions, it remains unknown whether ghrelin increases cardiac contractility and improves vascular responsiveness to vasoactive agents in severe sepsis.

METHODS:

Male adult rats were subjected to sepsis by cecal ligation and puncture (CLP). At 5 h after CLP, a bolus intravenous injection of 2 nmol ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed mini-pump over 15 h. At 20 h after CLP (i.e., severe sepsis), the maximal rates of ventricular pressure increase (+dP/dt(max)) and decrease (-dP/dt(max)) were determined in vivo. In additional groups of animals, the thoracic aortae were isolated at 20 h after CLP. The aortae were cut into rings, and placed in organ chambers. Norepinephrine (NE) was used to induce vascular contraction. Dose responses for an endothelium-dependent vasodilator, acetylcholine (ACh), and an endothelium-independent vasodilator, nitroglycerine (NTG) were carried out.

RESULTS:

+dP/dt(max) and -dP/dt(max) decreased significantly at 20 h after CLP. Treatment with ghrelin significantly increased +dP/dt(max) and -dP/dt(max) by 36% (P < 0.05) and 35% (P < 0.05), respectively. Moreover, NE-induced vascular contraction and endothelium-dependent (ACh-induced) vascular relaxation decreased significantly at 20 h after CLP. Administration of ghrelin, however, increased NE-induced vascular contraction and ACh-induced vascular relaxation. In contrast, no significant reduction in NTG-induced vascular relaxation was seen in rats with severe sepsis irrespective of ghrelin treatment.

CONCLUSIONS:

Ghrelin may be further developed as a useful agent for maintaining cardiovascular stability in severe sepsis.

• Authors: Rongqian Wu, Wayne W Chaung, Weifeng Dong, Youxin Ji, Rafael Barrera, Jeffrey Nicastro, Ernesto P Molmenti, Gene F Coppa, Ping Wang
• Journal: The Journal of surgical research (J Surg Res) Vol. 178 Issue 1 Pg. 370-7 (Nov 2012) ISSN: 1095-8673 [Electronic] United States
• PMID: 22459289 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Ghrelin
• Hemoglobins
• Vasoconstrictor Agents
• Vasodilator Agents
• Acetylcholine
• Norepinephrine

Topics

• Acetylcholine (pharmacology)
• Animals
• Blood Gas Analysis
• Blood Pressure (drug effects, physiology)
• Cecum (injuries)
• Disease Models, Animal
• Ghrelin (pharmacology)
• Hematocrit
• Hemoglobins (metabolism)
• Infusion Pumps
• Male
• Myocardial Contraction (drug effects, physiology)
• Norepinephrine (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sepsis (drug therapy, physiopathology)
• Severity of Illness Index
• Vasoconstrictor Agents (pharmacology)
• Vasodilation (drug effects, physiology)
• Vasodilator Agents (pharmacology)
• Ventricular Function, Left (drug effects, physiology)
• Wounds, Stab (physiopathology)