Objectives:By accounting for influences of systemic acid-base disturbances, gut mucosal-arterial PCO2gradient (PiCO2- PaCO2) has been increasingly advocated as a more specific marker of splanchnic perfusion than PiCO2alone. We examined the stability of the PiCO2- PaCO2gradient compared with raw PiCO2measurements during induced systemic hypo- and hypercapnia.Design:A prospective animal study.Settings:A university research laboratory.Subjects:Twenty anesthetized, paralyzed, and mechanically ventilated mongrel dogs.Interventions:After a baseline period during which PaCO2was maintained near 40 torr, the animals were divided into four groups. Minute ventilation was then altered by adjusting tidal volume, frequency, or both to achieve group PaCO2values of 15, 20, 60, and 80 torr for groups 1 through 4, respectively. Portal blood flow was monitored and maintained near baseline levels by infusion of intravenous fluids. Intestinal PiCO2was measured continuously by using capnometric recirculating gas tonometry.Measurements and Main Results:Mean (± SE) aggregate baseline PiCO2- PaCO2was 16.9 ± 3.3 torr. After 60 mins of hypoventilation, PiCO2- PaCO2decreased to 14.2 ± 1.1 and to 13.7 ± 2.7 torr in groups 3 and 4, respectively (p= NS, compared with baseline for both). On the other hand, after 60 mins of hyperventilation, PiCO2- PaCO2increased to 37.9 ± 3.6 and 28.0 ± 6.3 torr in groups 1 and 2, respectively (p< .0001, compared with baseline for both).Conclusions:In this model of maintained portal blood flow, PiCO2- PaCO2remained essentially stable after hypoventilation but increased significantly after inducing hyperventilation. Our findings warrant cautious interpretation of PiCO2- PaCO2as an indicator of splanchnic perfusion during systemic hypocapnia.