REVERSAL OF MEDETOMIDINE INDUCED SEDATION BY ATIPAMEZOLE IN SHEEP

S391 INTRODUCTION: Medetomidine is a highly selective alpha-2 agonist with sedative properties. The alpha-2 antagonist, atipamezole, reverses medetomidine induced sedation in animals. Sedative doses of alpha-2 agonists may change cardiac output and organ blood flow. The aim of this study was to investigate changes in cardiac output and organ blood flow induced by medetomidine and reversed by atipamezole in sheep. METHODS: With the approval of the Animal Care Committee, we studied 8 sheep. Animals were chronically instrumented with catheters in the left atrium, femoral artery and vein and a thermodilution pulmonary artery catheter. Medetomidine was infused in the femoral vein using a computer-controlled infusion pump targeting plasma levels of 0, 0.8, 1.6, 3.2, 6.4 and 12.8 ng/ml for 20 minutes each, followed by a 5 minute infusion of atipamezole (170 ug/kg). Hemodynamic values and organ blood flow (using coloured microspheres) were measured just prior to medetomidine infusion (baseline), at the end of each of the 5 medetomidine infusion steps, and 30 minutes after administration of atipamezole. Data were analyzed by repeated measures ANOVA followed by Dunnett's test. P<0.05 was considered significant. Data are mean +/- SD RESULTS: All animals fell asleep during medetomidine infusion and awoke within 5 minutes from the start of atipamezole infusion. Medetomidine (12.8 ng/ml) increased mean arterial pressure (MAP) from 107 +/- 10 to 134 +/- 16 mmHg, systemic vascular resistance (SVR) from 1310 +/- 207 to 3467 +/- 1299 dynes[center dot]s[center dot]cm-5, decreased heart rate from 96 +/- 14 to 67 +/- 23 bpm and cardiac output (CO) from 6.3 +/- 1.0 to 3.3 +/- 0.7 l/min. Blood flow decreased in heart, brain, kidney, skeletal muscle and intestine but increased in liver (Table 1). After atipamezole SVR and MAP returned to baseline, CO remained below baseline at 5.8 +/- 1.1 l/min and HR increased above baseline to 124 +/- 33 bpm. Blood flow increased to above baseline values in skeletal muscle but remained significantly below baseline in heart, brain and kidney (Table 1).Table 1: Percentage changes from baseline in organ blood flowDISCUSSION: Atipamezole did not reverse medetomidine induced reduction in cardiac, cerebral and renal blood flow. However, skeletal muscle blood flow increased to above baseline values. These results in sheep imply that high doses of alpha-2 agonists reversed by antagonists may cause considerable redistribution of organ blood flow in humans.