Metoclopramide: a novel adjunct for improving cardiac and hepatocellular functions after trauma-hemorrhage.
Although metoclopramide (MCP) administration after trauma-hemorrhage restores the depressed immune functions, it remains unknown whether this agent has any salutary effects on the depressed cardiovascular and hepatocellular functions under those conditions. Adult male Sprague-Dawley rats underwent a midline laparotomy (i.e., induction of soft-tissue trauma) and were then bled to and maintained at a mean arterial pressure (MAP) of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate (RL). The rats were then resuscitated with four times the shed blood volume in the form of RL over 60 min. MCP (2 mg/kg body wt) or vehicle was administered subcutaneously at the end of resuscitation. At 24 h after resuscitation, cardiac index and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined. Plasma levels of interleukin (IL)-6 and prolactin were also assayed. The results indicate that treatment with MCP after trauma-hemorrhage and resuscitation significantly improved the depressed cardiac output and hepatocellular function. Furthermore, MCP administration significantly increased circulating levels of prolactin and decreased the plasma levels of the proinflammatory cytokine IL-6. Thus, administration of MCP, which increased prolactin secretion, appears to be a useful adjunct for restoring the depressed cardiac and hepatocellular functions and downregulating inflammatory cytokine release after trauma and hemorrhagic shock.
Jarrar
D
D
Center for Surgical Research and Department of Surgery, Brown University School of Medicine and Rhode Island Hospital, Providence, Rhode Island 02903, USA.
Wang
P
P
Song
G Y
GY
Knöferl
M W
MW
Cioffi
W G
WG
Bland
K I
KI
Chaudry
I H
IH
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006470:Hemorrhage / Q000503:physiopathology*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014947:Wounds and Injuries / Q000503:physiopathology*
D018492:Dopamine Antagonists; D015850:Interleukin-6; D011388:Prolactin; D008787:Metoclopramide