Effects of captopril on hemodynamic and metabolic parameters in awake endotoxemic Yucatan minipigs

Angiotensin II (AII), a potent vasoconstrictor, contributes to ischemic and decompensatory phases of shock. Captopril may benefit vital organ and tissue perfusion by inhibiting AII formation. We fitted 13 approximately 50-kg pigs with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate portosystemic and transhepatic kinetics. We placed them in slings 72 hr later and following a 3-hr control period, they were infused with E. coli endotoxin at 15 micrograms/kg/hr for 6 hr. We kept eight as controls and five received a primed (2 mg/kg) continuous infusion (2 mg/kg/hr) of captopril 1 hr after initiation of endotoxin. Arterial hypotension developed by 60 min and hypoglycemia by 100 min in both groups; captopril had no effect on these parameters. Blood lactate increased from 7.8-32.1 mg/dl 80 min postendotoxin, and for the third to fifth hours of endotoxin infusion was significantly higher than those of the control group. 6-3H-glucose-derived appearance (Ra) values remained at 1.88-2.35 mg/kg/min throughout the experiment. Glucose disappearance (Rd) values were elevated from 60-120 min of endotoxin, increasing to 2.68-3.13 mg/kg/min versus 1.86 mg/kg/min preendotoxin. These changes corresponded to those in lactate, and incurred only a brief significant net glucose deficit (%Rd-%Ra) that peaked at 61.1% at 100 min. For 140-360 min postendotoxin, glucose balance was at most 8.3% in deficit (200 min) and 13.6% in positive balance (280 min) versus a net deficit of up to 25.4% (220 min) for the untreated group for much of the experiment. Portal and hepatic venous blood flow in captopril-treated pigs was lower than that in untreated pigs before endotoxin (8.2 and 10.0 ml/kg/min versus 12.9 and 17.9 ml/kg/min, respectively), but was not depressed following endotoxin infusion, versus 50% reductions in the untreated pigs, postendotoxin. Captopril maintained hepatosplanchnic blood flow and effected modest improvements in glucose kinetics.