The effects of L-659,066, a peripheral α2-adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep

We investigated whether administration of L-659,066, a peripheral alpha(2)-adrenoceptor antagonist, or verapamil, a calcium-channel antagonist, would prevent the cardiovascular effects of dexmedetomidine. Eleven sheep received three intravenous treatments with a randomized, cross-over design: dexmedetomidine (5 mu g/kg, DEX); DEX with L-659,066 (250 mu g/kg, DEX + L); and verapamil (0.05 mg/kg) 10 min prior to DEX (Ver + DEX). Haemodynamics were recorded at intervals upto 40 min. Acute increases in mean arterial pressure (MAP) (106 +/- 10.7 to 120.8 +/- 11.7 mmHg), central venous pressure (CVP) (3.3 +/- 3.2 to 14.7 +/- 5.0 mmHg) and systemic vascular resistance (SVR) (1579 +/- 338 to 2301 +/- 523 dyne s/cm5), and decreases in cardiac output (CO) (5.36 +/- 0.87 to 3.93 +/- 1.30 L/min) and heart rate (HR) (88.6 +/- 15.3 to 49.7 +/- 5.5/min) were detected with DEX. The peak SVR remained lower after Ver + DEX (1835 +/- 226 dyne s/cm5) than DEX alone, but the other parameters did not significantly differ between these treatments. 2 min after drug delivery, differences between DEX and DEX + L were statistically significant for all measured haemodynamic parameters. With DEX + L, an early decrease in MAP (99.9 +/- 6.8 to 89.3 +/- 6.6 mmHg) was detected, and DEX + L induced a slight but significant increase in CVP and a decrease in HR at the end of the observation period, while SVR and CO did not significantly change. All animals were assessed as deeply sedated from 2-20 min with no differences between treatments. L-659,066 has great potential for clinical use to prevent the cardiovascular effects of dexmedetomidine mediated by peripheral alpha(2)-adrenoceptors, whereas the effects of verapamil were marginal.