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

Raekallio M. R., Honkavaara J. M., Vainio O. M. The effects of L-659,066, a peripheral α₂-adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep. J. vet. Pharmacol. Therap. 33, 434-438. We investigated whether administration of L-659,066, a peri...

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Published in:Journal of veterinary pharmacology and therapeutics 2010-10, Vol.33 (5), p.434-438
Main Authors: RAEKALLIO, M.R, HONKAVAARA, J.M, VAINIO, O.M
Format: Article
Language:English
Subjects:
Adrenergic alpha-2 Receptor Antagonists - pharmacology
Animals
Blood Pressure - drug effects
Calcium Channel Blockers - pharmacology
Cardiac Output - drug effects
cardiovascular system
Cross-Over Studies
dexmedetomidine
Dexmedetomidine - pharmacology
drug evaluation
Female
Heart Rate - drug effects
hemodynamics
Hypnotics and Sedatives - pharmacology
intravenous injection
L-659,066
Quinolizines - pharmacology
Sheep
Vascular Resistance - drug effects
verapamil
Verapamil - pharmacology
veterinary drugs
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Summary:Raekallio M. R., Honkavaara J. M., Vainio O. M. The effects of L-659,066, a peripheral α₂-adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep. J. vet. Pharmacol. Therap. 33, 434-438. We investigated whether administration of L-659,066, a peripheral α₂-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 μg/kg, DEX); DEX with L-659,066 (250 μg/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 α₂-adrenoceptors, whereas the effects of verapamil were marginal.
ISSN:0140-7783
1365-2885
DOI:10.1111/j.1365-2885.2009.01156.x