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Diltiazem preserves hepatic gluconeogenesis following hemorrhagic shock
E R Geller1, L D Higgins, N Drourr
1Department of Surgery, School of Medicine, State University of New York, Stony Brook 11794-8191.
Insights
Diltiazem resuscitation improved hepatic gluconeogenesis in rats experiencing hemorrhagic shock. This intervention enhanced the liver's glucose production capacity, even after prolonged shock, suggesting a potential therapeutic benefit.
Area of Science:
- Physiology
- Biochemistry
- Pharmacology
Background:
- Prolonged hemorrhagic shock leads to metabolic dysfunction, including impaired hepatic gluconeogenesis and altered glucose homeostasis.
- Previous research suggests diltiazem may improve survival in hemorrhagic shock models.
- Understanding the impact of diltiazem on hepatic gluconeogenesis during shock is crucial for developing effective resuscitation strategies.
Purpose of the Study:
- To investigate the effect of diltiazem-containing resuscitation on hepatic gluconeogenesis during early and late phases of hemorrhagic shock in a rat model.
- To assess the impact of diltiazem on the liver's capacity to produce glucose following hemorrhagic shock and resuscitation.
Main Methods:
- Male Sprague-Dawley rats were subjected to 30 or 120 minutes of hemorrhagic shock.
- Resuscitation was performed using lactated Ringer's (LR) solution with or without diltiazem (DZ).
- In situ liver perfusion was utilized to measure hepatic gluconeogenesis following resuscitation.
Main Results:
- Diltiazem resuscitation significantly increased hepatic glucose production in both early (30 min) and late (120 min) phases of hemorrhagic shock compared to controls.
- Treated rats demonstrated an improved gluconeogenic response to lactate and pyruvate substrate.
- Serum glucose concentration and portal venous flow did not differ significantly between groups.
Conclusions:
- Resuscitation with diltiazem enhances hepatic gluconeogenesis during and after prolonged hemorrhagic shock in rats.
- Diltiazem may mitigate the metabolic derangements associated with hemorrhagic shock by supporting liver glucose production.
- These findings suggest a potential role for diltiazem in improving metabolic recovery following severe hemorrhage.
Abstract:
Prolonged hemorrhagic shock is characterized by the progression from hyperglycemia to hypoglycemia and failure to respond to standard methods of resuscitation. Previous studies have shown that the transition to irreversible shock is accompanied by attenuation of hepatic gluconeogenic capacity and a rising level of intracellular calcium. Additionally, it has been observed that diltiazem improves survival following prolonged hemorrhagic shock in rats. We examined the effect of resuscitation containing diltiazem upon hepatic gluconeogenesis during early and late phases of hemorrhagic shock in a rat model. Fasted male Sprague-Dawley rats (250-350 g) were rapidly bled to a mean arterial pressure of 40 mm Hg for a period of 30 minutes (group A) or 120 minutes (group B). At the end of the hemorrhagic shock period, rats were randomized to resuscitation utilizing lactated Ringer's (LR) solution, or LR+diltiazem (DZ, 1.2 mg/kg). Following resuscitation, rats underwent laparotomy and in situ liver perfusion with an oxygenated 37 degrees C glucose-free Krebs solution via the portal vein. After equilibration, 5 mmol/L lactate and 0.5 mmol/L pyruvate were added to the perfusate as substrate and effluent samples collected. Serum glucose concentration and portal venous flow did not differ significantly between DZ and LR groups throughout the study periods. In group A, hepatic glucose production was significantly elevated in DZ animals when compared with controls (p < 0.05). A similar significant improvement in gluconeogenesis was observed following 120 minutes of hemorrhagic shock in group B (p < 0.05). Additionally, treated rats (DZ, both groups A and B) demonstrated improved gluconeogenic response to substrate when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)