title: 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.affiliation: Department of Surgery, Hofstra North Shore-LIJ School of Medicine, and The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.
authors.forename: Rongqian
authors.initials: R
authors.lastname: Wu
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Chaung
authors.forename: Weifeng
authors.initials: W
authors.lastname: Dong
authors.forename: Youxin
authors.initials: Y
authors.lastname: Ji
authors.forename: Rafael
authors.initials: R
authors.lastname: Barrera
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nicastro
authors.forename: Ernesto P
authors.initials: EP
authors.lastname: Molmenti
authors.forename: Gene F
authors.initials: GF
authors.lastname: Coppa
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002432:Cecum / Q000293:injuries; D004195:Disease Models, Animal; D054439:Ghrelin / Q000494:pharmacology*; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007260:Infusion Pumps; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D012720:Severity of Illness Index; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D014951:Wounds, Stab / Q000503:physiopathology
chemical_list: D054439:Ghrelin; D006454:Hemoglobins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000109:Acetylcholine; D009638:Norepinephrine