Cardiovascular reflex responses after intrathecal omega-conotoxins or dexmedetomidine in the rabbit.
1. The effects of thoracic intrathecal doses (1 microg/kg) of the alpha2-adrenoceptor agonist dexmedetomidine and omega-conotoxins MVIIA and CVID on vasoconstrictor and heart rate responses to acute central hypovolaemia were studied in seven chronically instrumented rabbits. 2. Gradual inflation of an inferior vena cava cuff to reduce cardiac index (CI) by 8% per minute induced progressive vasoconstriction and an increase in heart rate (phase I). At approximately 40% of resting CI, there was sudden decompensation with failure of vasoconstriction and decrease in mean arterial pressure (MAP; phase II). 3. Both intrathecal MVIIA and CVID decreased resting CI (by 20% at 3 h), but only MVIIA significantly reduced resting MAP (P = 0.003). Dexmedetomidine resulted in transient bradycardia, but no other significant change in the resting circulation. With simulated haemorrhage, the relationship between CI and vascular conductance was shifted after MVIIA (1-3 h after injection) so that there was less vasoconstriction and a reduced increase in heart rate by the end of phase I compared with other treatments (P = 0.002 and P = 0.009, respectively). One hour after injection, dexmedetomidine reduced the slope of the phase I vasoconstrictor response (P = 0.03), but did not significantly alter the end-point of the response. With failure of vasoconstriction and the onset of phase II, vascular conductance was higher after MVIIA compared with controls. Both conotoxins caused progressive failure of vasoconstriction rather than recovery during phase II (P < 0.001). 4. Intrathecal injections of these drugs to control chronic pain may compromise cardiovascular responses to changes in central blood volume. At the single doses studied, there were significant differences between the responses to simulated haemorrhage after MVIIA or dexmedetomidine compared with CVID, with the prolonged effect after MVIIA most likely to be of clinical significance.
Blake
Duncan W
DW
Department of Pharmacology, The University of Melbourne, Parkville, Victoria, Australia. Duncan.Blake@mh.org.au
Wright
Christine E
CE
Scott
David A
DA
Angus
James A
JA
D000818:Animals; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006470:Hemorrhage / Q000139:chemically induced / Q000503:physiopathology; D007278:Injections, Spinal; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects; D020960:omega-Conotoxins / Q000008:administration & dosage / Q000633:toxicity*
D020960:omega-Conotoxins; D020927:Dexmedetomidine