| HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism. | |
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MedLine Citation:
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PMID: 15045166 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To assess the effects of the potassium ATP (KATP) channel blocker HMR1402 (HMR) on systemic and hepato-splanchnic hemodynamics, oxygen exchange and metabolism during hyperdynamic porcine endotoxemia. DESIGN: Prospective, randomized, controlled study with repeated measures. SETTING. Animal laboratory. SUBJECTS: Eighteen pigs allocated to receive endotoxin alone (control group, CON, n=10) or endotoxin and HMR (6 mg/kg h(-1), n=8). INTERVENTIONS: Anesthetized, mechanically ventilated, and instrumented pigs receiving continuous i.v. endotoxin were resuscitated with hetastarch to maintain mean arterial pressure (MAP) >60 mmHg. Twelve hours after starting the endotoxin infusion, they received HMR or its vehicle for another 12 h. RESULTS: HMR transiently increased MAP by about 15 mmHg, but this effect was only present during the first 1 h of infusion. The HMR decreased cardiac output due to a fall in heart rate, and thereby reduced liver blood flow. While liver O(2) delivery and uptake remained unchanged, HMR induced hyperlactatemia [from 1.5 (1.1; 2.0), 1.4 (1.2; 1.8), and 1.2 (0.8; 2.0) to 3.1 (1.4; 3.2), 3.2 (1.6; 6.5), and 3.0 (1.0; 5.5) mmol/l in the arterial, portal and hepatic venous samples, respectively] and further increased arterial [from 8 (3; 13) to 23 (11; 57); p<0.05], portal [from 9 (4; 14) to 23 (14; 39); p<0.05] and hepatic vein [from 7 (0; 15) to 30 (8; 174), p<0.05] lactate/pyruvate ratios indicating impaired cytosolic redox state. CONCLUSION: The short-term beneficial hemodynamic effects of KATP channel blockers have to be weighted with the detrimental effect on mitochondrial respiration. |
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Authors:
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Pierre Asfar; Zsolt Iványi; Hendrik Bracht; Balázs Hauser; Antje Pittner; Damian Vassilev; Marek Nalos; Xavier Maurice Leverve; Uwe Bernd Brückner; Peter Radermacher; Gebhard Fröba |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-03-26 |
Journal Detail:
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Title: Intensive care medicine Volume: 30 ISSN: 0342-4642 ISO Abbreviation: Intensive Care Med Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-05 Completed Date: 2004-09-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7704851 Medline TA: Intensive Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 957-64 Citation Subset: IM |
Affiliation:
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Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Parkstrasse 11, 89073 Ulm, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Pressure / drug effects Endotoxemia / drug therapy*, metabolism Female Lactates / blood Liver / metabolism Male Oxygen Consumption Potassium Channel Blockers / blood, therapeutic use* Pyruvates / blood Swine Thiourea / analogs & derivatives, blood, therapeutic use* |
| Chemical | |
Reg. No./Substance:
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0/1-((5-(2-(5-chloro-o-anisamido)ethyl)-beta-methoxyethoxyphenyl)sulfonyl)-3-methylthiourea, sodium salt; 0/Lactates; 0/Potassium Channel Blockers; 0/Pyruvates; 62-56-6/Thiourea |
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