Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2003
Detection of acute tolerance to the analgesic and nonanalgesic effects of remifentanil infusion in a rabbit model.
Although acute tolerance to analgesia develops rapidly with remifentanil, it is unknown whether acute tolerance also develops to its nonanalgesic effects. We investigated the analgesic and cardiorespiratory effects of remifentanil during a continuous infusion in a rabbit model. Ten tracheotomized New Zealand White rabbits with arterial and venous accesses were placed on a sling that allowed for reasonably free movement. In spontaneously breathing conscious animals, remifentanil was infused IV at a constant-rate of 0.3 microg kg(-1)x min(-1) for 360 min. Sedative/analgesic and cardiorespiratory variables were assessed repeatedly during remifentanil infusion, including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and subcutaneous electrical stimulation thresholds required to elicit head lift (HLT: pain detection/arousal threshold) and escape movement responses (EMT: pain tolerance threshold). Within 60-120 min of starting the infusion, the number of nonresponders, HLT, EMT, and PaCO(2) increased significantly, whereas blood pressure, heart rate, and respiratory rate decreased. Thereafter, all variables returned towards preinfusion levels despite continuing infusion. These results indicate that during a remifentanil infusion acute tolerance develops for both its analgesic and cardiorespiratory effects. ⋯ Using a new rabbit model, we found that during continuous, constant-rate remifentanil infusion acute tolerance developed within the first few hours, not only to its analgesic but also to its cardiovascular and respiratory effects, albeit in slightly different time courses.
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Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. To investigate the vasoconstrictive activity of this derivative, we performed functional examinations with dopamine treated with ONOO(-1) or 3-morpholinosydonimine-N-ethyl-carbamine (SIN-1; an ONOO(-1) producer) on isolated strips of rat thoracic aorta. To exclude the direct effect of ONOO(-1), the strips were pretreated with methylene blue, a guanylyl cyclase inhibitor. Dopamine induced concentration-dependent contraction, but dopamine pretreated with ONOO(-1) decreased the contraction in an ONOO(-1)-concentration-dependent manner. Both maximum contractions and 50% effective concentration values for dopamine-induced vasocontraction were significantly decreased by pretreatment with ONOO(-1). Dopamine incubated with SIN-1 also decreased the contraction, the decrease being dependent on the incubation time. ONOO(-1) formation is a favored reaction and occurs easily when cellular production of both nitric oxide and superoxide increases, as in septic shock. These results may, at least in part, account for dopamine's limitation as a vasoconstrictor in septic shock. ⋯ Peroxynitrite (ONOO(-1)) reacts with dopamine to form an oxidized derivative. We investigated the vasoconstrictive activity of this derivative with functional examinations using rat thoracic aorta and found the activity decreased. As ONOO(-1) formation increases in septic shock, our results may account for dopamine's limitation as a vasoconstrictor in septic shock.