Biomedical subjects

E R Schiffer

Publications and source records attributed to E R Schiffer.

4 recordsLinked to original sources

PubMed2000

Hepatic haemodynamic changes following inhibition of endothelium-derived relaxing and hyperpolarising factors in anaesthetised miniature pigs.

The influence of endothelium-dependent vasodilatation in regulating the hepatic circulation has been investigated by intraportal infusion of inhibitors of either endothelium-derived relaxing factor (NG-nitro-L-arginine-methyl-ester [L-NAME]) or of endothelium-derived hyperpolarising factor (ATP-dependent K(+)-channel inhibitor, glybenclamide) in barbiturate anaesthetised miniature pigs. Intraportal infusion of acetylcholine (5.5 micrograms kg-1 min-1 over 2 min) produced a selective 3-fold increase in hepatic artery and coeliac trunk blood flow, while mesenteric, portal, systemic, and pulmonary vascular beds remained unchanged. Intraportal L-NAME or glybenclamide did not reduce the hepatic artery and coeliac trunk flows but increased systemic and mesenteric vascular resistances. The acetylcholine-induced hepatic artery vasodilatation was partially blocked by 59%, 76% and 66% by L-NAME, at 30, 100, and 300 mg/kg respectively. Glybenclamide pretreatment up to 3 mg/kg did not modify acetylcholine-induced vasodilatation of the hepatic artery and coeliac trunk. Furthermore, prior cyclooxygenase inhibition did not alter the hepatic vascular response to acetylcholine. These results suggest that, in contrast to what is observed in large vessels, the hepatic vascular tree may not be entirely regulated by nitric oxide under basal conditions, but nitric oxide is released readily upon stimulation with acetylcholine, a response that is largely but incompletely blocked by L-NAME pretreatment. Neither basal vascular tone nor acetylcholine-induced vasorelaxation are mediated by the opening of glybenclamide-sensitive K+ channels in the hepatic circulation in pigs.

Acetylcholine↗

PubMed1998

Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia.

OBJECTIVE: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep. DESIGN: Randomised, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 12 adult instrumented, midazolam-sedated sheep. INTERVENTIONS: The animals were randomised to receive a 20-min continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10 microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25-30% increase in cardiac output by all three drugs during control conditions. MEASUREMENTS AND RESULTS: Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO2) and consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO2 and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO2 (especially in the coeliac trunk) observed during control conditions. CONCLUSIONS: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO2 and VO2.

Animals↗

PubMed1995

Systemic and splanchnic oxygen supply-demand relationship with fenoldopam, dopamine and noradrenaline in sheep.

The effects of intravenous administration of fenoldopam (0.3-10 micrograms.kg-1.min-1), dopamine (1-10 micrograms.kg-1.min-1) and noradrenaline (0.1-1 micrograms.kg-1.min-1) on systemic and splanchnic haemodynamics and oxygen supply-demand relationship were studied in 12 chronically instrumented, sedated sheep. Fenoldopam produced dose-dependent peripheral and splanchnic vasodilatation without change in arterial blood pressure. The coeliac trunk and portal vein blood flows were particularly sensitive to fenoldopam, whereas dopamine vasodilated these vascular beds only at high doses. Renal blood flow was not influenced by dopamine or fenoldopam, but decreased by noradrenaline. Fenoldopam maintained systemic oxygen extraction constant by increasing both oxygen supply and demand, while noradrenaline and dopamine increased oxygen supply more than demand, thus decreasing oxygen extraction. Both dopamine and fenoldopam increased oxygen delivery to the splanchnic organs while noradrenaline reduced it. Splanchnic oxygen consumption decreased with noradrenaline and increased with dopamine, resulting in a conserved oxygen extraction with both drugs, whereas oxygen consumption remained constant at all doses of fenoldopam infusion (i.e. dose-dependent decreased oxygen extraction). Both noradrenaline and fenoldopam, but not dopamine, were accompanied by increased portal lactataemia. We conclude that in sheep fenoldopam is a potent and selective splanchnic vasodilator but without vasodilatator effect on the renal circulation. The portal lactataemia associated with a decreased splanchnic oxygen extraction may present a significant limitation for some clinical applications of this drug.

Animals↗

PubMed1993

Sequential changes in the splanchnic circulation during continuous endotoxin infusion in sedated sheep: evidence for a selective increase of hepatic artery blood flow and loss of the hepatic arterial buffer response.

On-line recording of the sequential changes in systemic, pulmonary, mesenteric, hepatic and renal circulations during onset of endotoxaemia and at 24 h of established hyperdynamic sepsis were evaluated in seven chronically instrumented and sedated sheep receiving a continuous intravenous infusion of Escherichia coli endotoxin (20 ng min-1 kg-1). A transient and significant (P < 0.05) pulmonary arterial vaso-constriction was noted after 13 +/- 4 min, and was followed immediately by a simultaneous significant decrease of coeliac trunk, superior mesenteric artery, and portal vein blood flow to below 50% of baseline values. The superior mesenteric artery and portal vein blood flows partially recovered pre-endotoxin levels to 69 and 75% of baseline, respectively, after 70 min of endotoxin infusion. In contrast, the coeliac trunk blood flow remained reduced for a more prolonged period of time, but then completely recovered baseline values at 100 min. The response of the hepatic artery was biphasic, and consisted of a transient (5-10 min) vasoconstriction at 40 min followed by transitory increase of hepatic artery blood flow reaching a maximum of 921% of baseline values at 102 min. Contrasting with the early changes observed in mesenteric vascular resistances mostly unrelated to systemic haemodynamics, the response of the renal vasculature appeared to be more dependent on changes of renal perfusion pressure. A follow-up at 24 h revealed that the continuous intravenous infusion of endotoxin reproduced some of the most characteristic features of human sepsis with increased cardiac output and decreased vascular resistances of all vascular beds. We conclude that hepatic artery blood flow is selectively and considerably increased in early endotoxaemia in sheep independently of changes in portal vein blood flow, suggesting a disregulation of the physiologic hepatic arterial buffer response, most probably secondary to an increased liver oxygen demand required for phagocytosis, transport, and digestion of the the sudden overload of bacterial endotoxins.

Animals↗