sodium-oxybate and Ischemia

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.

Topics: Animals; Cricetinae; Disease Models, Animal; Hemodynamics; Hypertonic Solutions; Intestines; Ischemia; Male; Mesocricetus; Microcirculation; Shock, Hemorrhagic; Sodium Chloride; Sodium Oxybate; Splanchnic Circulation

The purpose of this study was to determine whether gamma-hydroxybutyrate provides protection against intestinal ischemia/reperfusion injury and to compare its effect with that of allopurinol and vitamin E. Thirty minutes of total regional ischemia, followed by 3 hours of reperfusion, produced intestinal damage that was completely prevented by gamma-hydroxybutyrate pretreatment. Naloxone partially blocked this protective effect. Allopurinol provided only partial protection against this injury, whereas vitamin E provided none. Treatment with gamma-hydroxybutyrate after ischemia but before reperfusion also provided significant protection. This study clearly demonstrates that gamma-hydroxybutyrate provides significant protection against intestinal ischemic injury and that it may do so via an opiate receptor-mediated mechanism.

Topics: Allopurinol; Animals; Cricetinae; Hydroxybutyrates; Intestines; Ischemia; Male; Mesocricetus; Naloxone; Reperfusion Injury; Sodium Oxybate; Vitamin E

Topics: Forearm; Hand; Humans; Hydroxybutyrates; Hypoxia; Ischemia; Microcirculation; Sodium Oxybate; Tourniquets

Posttraumatic spinal cord blood flow (SCBF) was assessed after elevating the mean systemic arterial pressure (mSAP) with a blood transfusion, or with an infusion of dopamine. The effect of the anesthetic agent, gamma hydroxybutyrate, was also assessed. Flows were measured using the 14C-antipyrine autoradiographic method. Animals were injured at T-1 by acute compression of the spinal cord with a clip exerting a pressure of 175 gm. Uninjured animals, with mSAP's of 120.0 +/- 17.0 mm Hg, had gray and white matter flows of 74.2 +/- 22.3 and 18.7 +/- 6.7 ml/100 gm/min, respectively, while injured untreated animals had mSAP's of 82.5 +/- 14.1 mm Hg and gray and white matter flows of 13.3 +/- 12.1 and 3.9 +/- 3.9 ml/100 gm/min, respectively, at the injury site. Blood transfusion raised the mSAP's to 127.5 +/- 13.7 mm Hg in the injured animals and doubled the flows in gray and white matter to 25.6 +/- 30.2 and 6.3 +/- 6.4 ml/100 gm/ml, respectively. Dopamine did not have as beneficial an effect as blood transfusion on either the mSAP (101.0 +/- 16.7 mm Hg) or the SCBF (gray and white matter flows of 18.4 +/- 12.4 and 5.8 +/- 5.9 ml/100 gm/min). Gamma hydroxybutyrate (GHB) had almost no effect on the mSAP or SCBF of normal animals, and in injured animals produced only a unilateral increase in flow on the less severely injured side, without affecting the mSAP.

Topics: Animals; Autoradiography; Blood Pressure; Blood Transfusion; Carbon Dioxide; Dopamine; Female; Hydroxybutyrates; Ischemia; Partial Pressure; Rats; Regional Blood Flow; Sodium Oxybate; Spinal Cord; Spinal Cord Injuries