Document Detail


HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism.
MedLine Citation:
PMID:  15045166     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-03-26
Journal Detail:
Title:  Intensive care medicine     Volume:  30     ISSN:  0342-4642     ISO Abbreviation:  Intensive Care Med     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-05     Completed Date:  2004-09-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7704851     Medline TA:  Intensive Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  957-64     Citation Subset:  IM    
Affiliation:
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Parkstrasse 11, 89073 Ulm, Germany.
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MeSH Terms
Descriptor/Qualifier:
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:
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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