Recovery of hepatocellular ATP and 'pericentral apoptosis' after hemorrhage and resuscitation
| Autor: | Markus Paxian, Hartmut Jaeschke, T. Beate Wolf, Silke Jeblick, Stefan A. Kolb, Michael Bauer, Hauke Rensing, Inge Bauer, Andre Stockhausen, Angelika E. M. Mautes |
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| Rok vydání: | 2003 |
| Předmět: |
Indocyanine Green
Male medicine.medical_specialty Resuscitation Necrosis Apoptosis Cysteine Proteinase Inhibitors Shock Hemorrhagic Biology Biochemistry Antioxidants Amino Acid Chloromethyl Ketones Cyclic N-Oxides Rats Sprague-Dawley chemistry.chemical_compound Adenosine Triphosphate Ischemia Internal medicine Genetics medicine Animals Molecular Biology Hemorrhagic hypotension Caspase Inhibitors Rats Blood pressure Endocrinology Liver chemistry Anesthesia Hepatocytes DNA fragmentation Spin Labels Hypotension medicine.symptom Liver dysfunction Indocyanine green Biotechnology |
| Zdroj: | The FASEB Journal. 17:993-1002 |
| ISSN: | 1530-6860 0892-6638 |
| DOI: | 10.1096/fj.02-0624com |
| Popis: | Progressive liver dysfunction contributes significantly to the development of multiple organ failure after trauma/hemorrhage. This study tested the relative impact of necrotic and apoptotic cell death in a graded model of hemorrhagic shock (mean arterial blood pressure=35+/-5 mmHg for 1, 2, or 3 h, followed by 2 h, 1 h, or no resuscitation, respectively) in rats. Prolonged periods of hemorrhagic hypotension (3 h) were paralleled by a profound decrease of hepatic ATP levels and occurrence of pericentral necrosis. Resuscitation after shorter periods of hemorrhagic hypotension resulted in restoration of tissue ATP whereas hepatocellular function as assessed by indocyanine green clearance remained depressed (49.9+/-1.6 mL/(min x kg) at baseline, 28.8+/-1.2 mL/(min x kg) after 2 h of resuscitation; P0.05). Under these conditions, induction of caspase activity and DNA fragmentation were observed in pericentral hepatocytes that could be prevented by the radical scavenger tempol. Pretreatment with z-Val-Ala-Asp(O-methyl)-flouromethylketone prevented de novo expression of caspase-generated cytokeratin 18, DNA fragmentation, and depression of hepatocellular indocyanine green clearance. These data suggest that prolonged low flow/hypoxia induces ATP depletion and pericentral necrosis and restoration of oxygen supply and ATP levels after shorter periods of low flow ischemia propagate programmed cell death or "pericentral apoptosis." |
| Databáze: | OpenAIRE |
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