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Diltiazem administration after crystalloid resuscitation restores active hepatocellular function and hepatic blood
1Department of Surgery, Michigan State University, East Lansing 48824-1315.
Insights
Diltiazem improved liver function and blood flow after hemorrhagic shock in rats. This calcium antagonist may aid trauma and hemorrhage treatment, even without blood resuscitation.
Area of Science:
- Hepatocellular function
- Hemorrhagic shock
- Calcium antagonists
Background:
- Hemorrhagic shock depresses active hepatocellular function despite fluid resuscitation.
- Calcium antagonists offer protective effects against ischemia and shock.
- The impact of calcium antagonists on liver function post-trauma and hemorrhage is not well understood.
Purpose of the Study:
- To investigate the effects of diltiazem on depressed hepatocellular function and hepatic blood flow in a rat model of trauma and hemorrhage.
- To assess if diltiazem can mitigate negative impacts on liver function and blood flow following severe injury and blood loss.
Main Methods:
- Rats underwent laparotomy and controlled hemorrhage, followed by Ringer's lactate resuscitation.
- Diltiazem was administered intravenously during and after resuscitation.
- Active hepatocellular function (Vmax, Km), effective hepatic blood flow (EHBF), and hepatic microvascular blood flow (HMBF) were measured.
Main Results:
- Resuscitation led to significant decreases in Vmax, Km, EHBF, and HMBF.
- Diltiazem infusion successfully restored Vmax, Km, EHBF, and HMBF.
- Diltiazem also prevented the development of hepatic edema.
Conclusions:
- Diltiazem administration can restore hepatocellular function and hepatic blood flow after trauma and hemorrhage.
- Diltiazem shows potential as a therapeutic adjunct in managing severe hemorrhage and trauma.
- These benefits were observed even without the use of blood products for resuscitation.
Abstract:
Studies have shown that active hepatocellular function is depressed after hemorrhagic shock, despite crystalloid resuscitation. It is also known that calcium antagonists produce various beneficial effects on cell and organ function after ischemia and shock. However, it remains unknown whether such agents have any salutary effects on the depressed active hepatocellular function and hepatic blood flow in a nonheparinized model of trauma and hemorrhage. To study this, rats underwent a midline laparotomy (trauma-induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximum bleedout was returned in the form of Ringer's lactate. They were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 minutes, during and after which diltiazem (400 micrograms/kg body weight) was infused intravenously over 95 minutes. Active hepatocellular function (Vmax and Km) was determined with an in vivo indocyanine green clearance technique. Effective hepatic blood flow (EHBF) was determined by Fick principle and corrected by the indocyanine green extraction ratio. Hepatic microvascular blood flow (HMBF) was measured by laser Doppler flowmetry. Results indicate that Vmax, Km, EHBF, and HMBF decreased significantly at 1.5 and 4 hours after resuscitation. Diltiazem infusion restored the depressed Vmax, Km, EHBF, and HMBF and prevented the occurrence of hepatic edema. Thus, diltiazem may be a useful adjunct in the treatment of trauma and severe hemorrhage even in the absence of blood resuscitation.