Effects of fentanyl, and the antagonism by naloxone, on regional blood flow and biochemical variables in conscious rabbits.

Effects of fentanyl (cumulative doses: 25, 75 and 125 micrograms.kg-1, i.v.) on respiratory, systemic and regional haemodynamic and biochemical variables were studied in the conscious rabbit. The initial dose of fentanyl (25 micrograms.kg-1) produced a rise in blood pressure and a decrease in heart rate but, on subsequent doses, smaller effects were observed. The drug produced changes in arterial blood gases which were due to a severe decrease in respiratory frequency and an increase in muscular rigidity of chest and neck muscles. The blood flow to skin, stomach, mesentery plus pancreas, bones and fat was decreased by fentanyl. These changes resemble those obtained during alpha-adrenergic stimulation and, thus, may be related to a release of catecholamines during respiratory depression. On the contrary, however, hepatic arterial blood flow was increased and this effect may be responsible for the rapid metabolism and a short duration of action of fentanyl. Fentanyl also caused an increase in the concentration of glucose, lactate and inorganic phosphates in the arterial blood. These changes are probably due to hypoxia. Administration of naloxone not only reversed the residual effects of previous fentanyl administration but also antagonized the respiratory, haemodynamic and biochemical responses to the morphinomimetic drug.