Reverse Physiology, i.e., Cellular Versus Integrative Versus Comparative Physiology? α-2 Agonists and Septic Shock (original) (raw)
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Effects of a selective iNOS inhibitor versus norepinephrine in the treatment of septic shock
Shock (Augusta, Ga.)
Inhibition of NOS is not beneficial in septic shock; selective inhibition of the inducible form (iNOS) may represent a better option. We compared the effects of the selective iNOS inhibitor BYK191023 with those of norepinephrine (NE) in a sheep model of septic shock. Twenty-four anesthetized, mechanically ventilated ewes received 1.5 g/kg body weight of feces into the abdominal cavity to induce sepsis. Animals were randomized into three groups (each n = 8): NE-only, BYK-only, and NE + BYK. The sublingual microcirculation was evaluated with sidestream dark-field videomicroscopy. MAP was higher in the NE + BYK group than in the other groups, but there were no significant differences in cardiac index or systemic vascular resistance. Mean pulmonary arterial pressure was lower in BYK-treated animals than in the NE-only group. PaO2/FiO2 was higher and lactate concentration lower in the BYK groups than in the NE-only group. Mesenteric blood flow was higher in BYK groups than in the NE-only...
Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock
Critical Care
Background Angiotensin II is one of the vasopressors available for use in septic shock. However, its effects on the septic myocardium remain unclear. The aim of the study was to compare the effects of angiotensin II and norepinephrine on cardiac function and myocardial oxygen consumption, inflammation and injury in experimental septic shock. Methods This randomized, open-label, controlled study was performed in 20 anesthetized and mechanically ventilated pigs. Septic shock was induced by fecal peritonitis in 16 animals, and four pigs served as shams. Resuscitation with fluids, antimicrobial therapy and abdominal drainage was initiated one hour after the onset of septic shock. Septic pigs were randomly allocated to receive one of the two drugs to maintain mean arterial pressure between 65 and 75 mmHg for 8 h. Results There were no differences in MAP, cardiac output, heart rate, fluid balance or tissue perfusion indices in the two treatment groups but myocardial oxygen consumption was...
Critical Care Medicine, 2006
Marked potassium efflux prevents calcium entry into vascular smooth muscle cells and may be responsible for the "vasoplegia" of septic shock. Blockade of adenosine triphosphate (ATP)-sensitive potassium channels restores vascular tone in animal studies of septic shock. The effect of such potassium channel blockade has not been previously studied in humans. To test whether the administration of an ATP-sensitive potassium (K(ATP)) channel blocker restores norepinephrine responsiveness in patients with septic shock. Randomized, double-blind, placebo-controlled crossover pilot study. Intensive care unit of a university hospital. Ten patients with septic shock requiring invasive hemodynamic monitoring and infusion of norepinephrine to maintain adequate mean arterial pressure. In addition to standard therapy, patients were randomized to initially receive either the K(ATP) channel blocker glibenclamide (20 mg) or placebo. Then, after 24 hrs, each patient crossed over to receive the alternative therapy. After the administration of the K(ATP) channel blocker glibenclamide, median norepinephrine requirements decreased from 13 to 4 microg/min compared with a change from 19 to 7 microg/min after placebo. The two changes represented a decrease of 78.9% and 71.1% in dose, respectively (p = .57, not significant). There were also no significant changes in heart rate, mean arterial blood pressure, and lactate concentration when comparing the study drug with placebo. Glibenclamide, however, induced a significant decrease in median blood glucose concentration (5.4 [inter-quartile range, 4.5-7.0] vs. 7.0 mmol/L [5.2-9.3], p < .0001) compared with placebo and increased the need for parenteral glucose administration. The K(ATP) channel blocker glibenclamide failed to achieve a greater reduction in norepinephrine dose than placebo in septic shock patients, although it caused a reduced glucose concentration. Our observations suggest that, in such patients, blockade of K(ATP) channels does not have a potent effect on vasomotor tone.