The effects of gammahydroxybutyrate on hypermetabolism and wound healing in a rat model of large thermal injury.
BACKGROUND
Growth hormone (GH) improves wound healing and ameliorates pediatric postburn tissue catabolism associated with deficient endogenous GH/IGF-1 levels. Expense, parenteral administration, and compliance have limited widespread usage. Gammahydroxybutyrate (GHB), an upstream neuromodulatory gamma-amino butyric acid (GABA) derivative, is known to increase slow wave sleep and stimulate endogenous GH secretion. In this study, improvement in GH levels in turn has been shown to accelerate wound healing.


METHODS
Body composition in male Sprague-Dawley rats with > or =40% total body surface area scald burn, receiving incremental GHB doses orally, was assessed by Dual Energy X-Ray Absorptiometry. Serum GH and IGF-1 levels were measured. Wound cross sections were scored semiquantitatively for wound healing variables.


RESULTS
Incremental elevation in GH and IGF-1 were associated with significantly improved wound edge epithelialization and cell-layer thickness at high doses (p < 0.005). However, body composition was similar to that of burned controls.


CONCLUSIONS
GHB sufficiently elevated serum GH and IGF-1 levels to significantly improve epithelialization rates and layer thickness at high doses. Substantially greater elevations of serum GH and IGF-1 levels are required in the rat burn model than for humans. GHB may improve postburn hypermetabolism in humans by elevating endogenous GH levels, though only improved epithelialization was demonstrated in this study.
Murphy
Kevin D
KD
Northern Ireland Plastic and Maxillofacial Service, The Ulster Hospital, Dundonald, Belfast, Ireland. kevindjmurphy@yahoo.co.uk
Rose
Mary W
MW
Chinkes
David L
DL
Meyer
Walter J
WJ
Herndon
David N
DN
Hawkins
Hal K
HK
Sanford
Arthur P
AP
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002056:Burns / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D013006:Growth Hormone / Q000187:drug effects / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000209:etiology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep; D012978:Sodium Oxybate / Q000494:pharmacology*; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D007334:Insulin-Like Growth Factor I; D012978:Sodium Oxybate; D013006:Growth Hormone