HMR1402, a potassium ATP channel blocker during hyperdynamic porcine endotoxemia: effects on hepato-splanchnic oxygen exchange and metabolism.

Autor:	Asfar, Pierre, Iványi, Zsolt, Bracht, Hendrik, Hauser, Balá;zs, Pittner, Antje, Vassilev, Damian, Nalos, Marek, Leverve, Xavier Maurice, Brückner, Uwe Bernd, Radermacher, Peter, Fröba, Gebhard, Iványi, Zsolt, Hauser, Balázs, Brückner, Uwe Bernd, Fröba, Gebhard
Předmět:	POTASSIUM ADENOSINE triphosphate HEMODYNAMICS HYDRODYNAMICS BLOOD circulation FLUID dynamics ANIMAL experimentation BLOOD pressure CARBOXYLIC acids CHEMICAL reagents COMPARATIVE studies LACTATES LIVER RESEARCH methodology MEDICAL cooperation RESEARCH SWINE EVALUATION research ENDOTOXEMIA OXYGEN consumption POTASSIUM antagonists THERAPEUTICS
Zdroj:	Intensive Care Medicine; May2004, Vol. 30 Issue 5, p957-964, 8p
Abstrakt:	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. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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