Dopamine-1 receptor stimulation impairs intestinal oxygen utilization during critical hypoperfusion

Effects of a dopamine-1 (DA-1) receptor agonist on systemic and intestinal oxygen delivery ((D) over dot O-2)-uptake relationships were studied in anesthetized dogs during sequential hemorrhage. Control (group 1) and experimental animals (group 2) were treated similarly except for the addition of fenoldopam (1.0 mug.kg(-1).min(-1)) in group 2. Both groups had comparable systemic critical (D) over dot O-2 ((D) over dot O-2crit), but animals in group 2 had a higher gut (D) over dot O-2crit (1.12 +/- 1.13 vs. 0.80 +/- 0.09 ml.kg(-1).min(-1), P < 0.05). At the mucosal level, a clear biphasic delivery-uptake relationship was not observed in group 1; thus oxygen consumption by the mucosa may be supply dependent under physiological conditions. Group 2 demonstrated higher peak mucosal blood flow and lack of supply dependency at higher mucosal (D) over dot O-2 levels. Fenoldopam resulted in a more conspicuous biphasic relationship at the mucosa and a rightward shift of overall splanchnic (D) over dot O-2crit despite increased splanchnic blood flow. These findings suggest that DA-1 receptor stimulation results in increased gut perfusion heterogeneity and maldistribution of perfusion, resulting in increased susceptibility to ischemia.