Administration of a matrix metalloproteinase inhibitor after hemorrhage improves cardiovascular and hepatocellular function

Shock
P WangI H Chaudry

Abstract

Although matrix metalloproteinase inhibitors prevent the increase in soluble tumor necrosis factor-alpha during endotoxemia, it remains unknown whether a novel matrix metalloproteinase inhibitor, GM6001, improves cardiovascular and hepatocellular function after trauma and hemorrhage. To determine this, rats underwent laparotomy (i.e., trauma-induced), and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal shed volume was returned in the form of Ringer's lactate. The animals were then resuscitated with 3 times the volume of maximal bleedout with Ringer's lactate over 45 min, followed by 2 times Ringer's lactate over 60 min. GM6001, at a dose of 100 mg/kg or an equal volume of normal saline, was administered subcutaneously 15 min before the completion of resuscitation. At 2 and 4 h after resuscitation, cardiac output was measured by indocyanine green (ICG) dilution. Hepatocellular function (i.e., maximum velocity and the efficiency of ICG clearance) was determined by in vivo ICG clearance. Microvascular blood flow in various organs was assessed by laser Doppler flowmetry. The results indicate that cardiac output, hepatocellular function, and tissue microvascular blood flow decreased significan...Continue Reading

Citations

Jun 10, 2003·Critical Care Medicine·Joachim F KueblerIrshad H Chaudry
Aug 9, 2003·Critical Care Medicine·Maria B Witte, Adrian Barbul
Apr 5, 2005·The Laryngoscope·Patrick J AntonelliPhilip J Barr
Jul 21, 2020·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Anoek L I van LeeuwenCharissa E van den Brom
Oct 22, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yuchen MaJoseph L Messina

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