title: Diltiazem administration after crystalloid resuscitation restores active hepatocellular function and hepatic blood flow after severe hemorrhagic shock.
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.
authors.affiliation: Department of Surgery, Michigan State University, East Lansing 48824-1315.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Z F
authors.initials: ZF
authors.lastname: Ba
authors.forename: R E
authors.initials: RE
authors.lastname: Dean
authors.forename: I H
authors.initials: IH
authors.lastname: Chaudry
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D007552:Isotonic Solutions; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012151:Resuscitation / Q000379:methods; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
chemical_list: D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D004110:Diltiazem