The cardiovascular effects of gamma-hydroxybutyrate following hemorrhage.
We have previously shown that gamma-hydroxybutyrate (GHB) protects the small intestine against ischemia/reperfusion injury. This study examined the effects of GHB on cardiovascular function and intestinal microcirculation following hemorrhage. Hypotension was induced in control group of hamsters by controlled hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Following 60 minutes of hypovolemia the shed blood was returned. This procedure resulted in complete intestinal mucosal microvascular stasis 2 hours following the return of shed blood. A second group of animals was treated with GHB (600 mg/kg body weight) and, despite the loss of 37% of total blood volume, GHB treatment completely prevented the microcirculatory stasis, following the reinfusion of shed blood. In male Wistar rats treated with GHB (200 mg/kg) after the induction of hemorrhage, blood pressure rapidly increased to pre-hemorrhage levels following treatment, even though the shed blood was not returned. Cardiac output (CO) also increased to pre-hemorrhage levels. Sodium chloride solution, in the same molar concentration as GHB (23% NaCl), produced much smaller, but statistically significant, increases in MAP and CO. In animals given an equal volume of normal saline, a gradual increase in MAP was observed, reaching statistical significance at 75 minutes following treatment. Three hours following hemorrhage, serum levels of creatine kinase were 3-fold higher, whereas aspartate aminotransaminase and alanine aminotransferase levels were 2-fold higher in both normal saline and hypertonic saline-treated animals than in GHB-treated animals. These experiments suggest that GHB can prevent ischemic complications following a hypovolemic episode and may improve survival following severe hemorrhage.
Boyd
A J
AJ
Aron M. Rappaport Microcirculation Laboratory, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.
Sherman
I A
IA
Saibil
F G
FG
D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D006982:Hypertonic Solutions / Q000008:administration & dosage; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000517:prevention & control*; D012965:Sodium Chloride / Q000008:administration & dosage; D012978:Sodium Oxybate / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects*
D006982:Hypertonic Solutions; D012965:Sodium Chloride; D012978:Sodium Oxybate