The effect of alpha(2) agonist-induced sedation and its reversal with an alpha(2) antagonist on organ blood flow in sheep

We investigated changes in cardiac output and organ blood flow induced by m edetomidine in sheep and determined changes in cardiac output and organ blo od flow after reversal of medetomidine-induced sedation by atipamezole. She ep were chronically instrumented. was infused TV to target plasma levels of 0, 0.8, 1.6, 3.2, 6.4, and 12.8 ng/mL for 25 min each, followed by a 5-min infusion of atipamezole. Hemodynamic values and organ blood flow (using co lored microspheres) were measured just before medetomidine infusion (baseli ne), at the end of each medetomidine infusion step, and 30 min after the ad ministration of atipamezole, Medetomidine (12.8 ng/mL) decreased cardiac ou tput from 6.3 +/- 1.0 to 3.2 +/- 0.7 L/min (P < 0.0001) and increased syste mic vascular resistance from 1310 +/- 207 to 3467 +/- 1299 dynes . s(-1) . cm(-5) (P < 0.0001). Blood flow decreased in the cerebral cortex from 1.29 +/- 0.40 to 0.66 +/- 0.12 mL . g(-1) . min(-1) (P < 0.0001), left ventricle from 2.11 +/- 0.61 to 1.40 +/- 0.40 mL . min(-1) (P < 0.0001), kidney from 8.28 +/- 3.17 to 6.07 +/- 2.65 mL . g(-1) . min (P < 0.0001), skin from 0. 09 +/- 0.04 to 0.05 +/- 0.02 mL . g(-1) . min(-1) (P < 0.0001), intestine f rom 0.56 +/- 0.13 to 0.27 +/- 0.07 mL . g(-1) . min(-1) (P < 0.0001), and s keletal muscle from 0.28 +/- 0.15 to 0.04 +/- 0.01 mL . g(-1) . min(-1) (P < 0.0001). Blood flow in the liver (hepatic artery) increased from 0.05 +/- 0.03 to 0.24 +/- 0.16 mL . g(-1) . min(-1) (P < 0.0001). After atipamezole infusion, cardiac output and systemic vascular resistance returned to base line, but the cerebral cortex, left: ventricle, and renal blood flows remai ned below baseline at 0.89 +/- 0.22, 137 +/- 0.50, and 6.25 +/- 2.76 mL . g (-1) . min(-1), respectively; skeletal muscle blood flow increased above ba seline to 0.44 +/- 0.27 mL . g(-1) . min(-1), spleen blood flow deceased be low baseline to 1.65 +/- 0.61 mL . g(-1) . min(-1) (P < 0.0001), and liver, intestine, and lung blood flows returned to baseline values. In conclusion , medetomidine decreased and redistributed organ blood flow in sheep. Atipa mezole reversed the medetomidine-induced hemodynamic changes, but redistrib uted blood flow from the brain, heart, and kidney to the skeletal muscle.