Hepatic O2 exchange and liver energy metabolism in hyperdynamic porcine endotoxemia: effects of iloprost

Abstract

Thus, in a clinically relevant model of human sepsis, iloprost did not produce potential adverse effects but rather ameliorated hepatic metabolic disturbances and, thereby, hepatic energy balance.

Effects of nicotinamide, an inhibitor of PARS activity, on gut and liver O2 exchange and energy metabolism during hyperdynamic porcine endotoxemia

“…Sixteen domestic pigs of either sex (40±55 kg) were investigated. The anesthesia as well as the surgical preparation have been previously described in detail [15,16,17]. Briefly, the pigs were anesthetized with pentobarbital (200±300 mg/kg) and paralyzed with alcuronium (14 mg/h).…”

“…On the basis of these promising data from rodent models, we investigated the effects of PARS inhibition in a porcine model of long-term, well-resuscitated, hyperdynamic and hypermetabolic endotoxemia as described recently [15,16,17]. Considering the postulated role of the hepato-splanchnic region in the pathogenesis of septic shock and multiple organ failure [18], we focused on the intestinal and liver perfusion, O 2 kinetics, and energy metabolism.…”

Heat shock protein 90 is responsible for hyperdynamic circulation in portal hypertensive rats

“…Indeed, the importance of splanchnic vasodilation in this process was highlighted by clinical utility of nonselective beta-blockers and octreotide, both of which could reduce splanchnic vasodilation and portal venous inflow [6] . However, cirrhotic vasculature was highly resistant to conventional vasopressors [7] , and attempts to correct the hyperdynamic circulation in cirrhosis by antagonism of putative endogenous vasodilator mediators have been unsuccessful so far [8,9] . Pressure and resistance changes in perfused mesenteric vasculature occurred, in part through NO-dependent mechanisms, and in experimental portal hypertension this vascular bed demonstrated a hyporeactivity to vasoconstrictors such as methoxamine (MTX), mainly due to excessive endothelium-derived NO production [10,11] .…”

Akutes Leberversagen

“…So verbessert Iloprost hier reversibel die Plasmaeliminationsrate von Indozyaningrün als Zeichen einer verbesserten Leberfunktion und -perfusion [81]. Beim Schwein steigert Iloprost in der Endotoxinämie den Leberblutfluss und schwächt die Endotoxin-induzierten Stö-rungen des zellulären Energiestoffwechsels ab; die erhöhte endogene Glukoseproduktion der Leber und die verminderte hepatische Laktataufnahme werden normalisiert [145]. Auch bei Patienten mit septischem Schock konnte unter Iloprostinfusion eine reversible Erhöhung des Blutflusses und der DO 2 im Splanchnikusgebiet und eine Reduktion der endogenen Glukoseproduktion nachgewiesen werden [71].…”