Vascular Reactions in Septic Shock and Multiple Organ Failure

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We investigated vascular reactions in human arteries, such as gastro-epiploic arteries, internal mammary arteries, and radial arteries, obtained from patients who were undergoing coronary artery bypass surgery(CABG).1)Systematic investigations of the actions of phosphodiesterase(PDE)3 inhibitors on different human vascular tissues have not been performed. Our results suggest different activities among the three PDE3 inhibitors in human arteries located in different regions. Moreover, these drugs differ in their potencies against the contractile responses to agonists such as NE and thromboxane A_2 in these arteries.2)The direct actions of dopamine on human arterial coronary bypass grafts are not well known. We investigated its effects on isolated rings cut from radial arteries(RA), gastroepiploic arteries(GEA), and internal mammary arteries(IMA) harvested from patients undergoing coronary artery bypass surgery. Our results suggest that differing affinities of the drug for DA_1- and α_1-adrenergic receptors may underline its variable contractile and vasorelaxing effects among these arteries.3)We investigated the direct effect of dexmedetomidine(DEX) on human resistance arteries in vitro. Gastroepiploic arteries were isolated from the omentum of gastrectomy specimens, the vascular endothelium was denuded, and the smooth muscle mechanical responses were measured. Our results indicate that DEX has dual α_2-adrenergic agonist and α_1-adrenergic antagonist actions in human isolated gastroepiploic arteries. The data presented here predict that DEX would have little direct effect on vascular reactivity under normal clinical conditions where steady-state plasma levels of DEX are generally less than 10^<-7> M. However, the direct α_2 agonist and α_1 antagonist actions observed with higher concentrations of DEX could significantly affect vascular tone under certain conditions.