Effect Of Fentanyl On Baroreflex Control Of Circumflex Coronary Conductance

• Published in: Clinical and Experimental Pharmacology and Physiology Vol. 27; no. 12; pp. 1028 - 1033
• Main Authors: Moore, Peter G, Quail, Anthony W, Cottee, David BF, McIlveen, Stephen A, White, Saxon W
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Science Pty 01-12-2000
• Subjects: Analgesics, Opioid - pharmacology; Anesthetics, Intravenous - pharmacology; Animals; arterial baroreflex; awake dog; Baroreflex; Blood Pressure; cardiac surgery; coronary blood flow; Coronary Circulation - physiology; Dogs; Dose-Response Relationship, Drug; Female; fentanyl; Fentanyl - pharmacology; Infusions, Intravenous; Male; Vascular Resistance; Vasodilation
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1046/j.1440-1681.2000.03371.x

SUMMARY
1. Fentanyl, a synthetic μ‐opioid receptor agonist, is the preferred induction and maintenance anaesthetic agent in cardiac surgery.
2. Its actions on myocardial blood flow are poorly understood. There are reports of intra‐operative myocardial ischaemia. Its reported actions on cardiorespiratory control vary widely, but do involve hypertension, bradycardia and peripheral vasoconstriction.
3. Accordingly, the postulate that fentanyl would cause coronary vasoconstriction and myocardial disadvantage was examined in awake dogs with a continuous wave Doppler flow probe mounted on the circumflex coronary artery.
4. Continuous intravenous infusion of fentanyl citrate (550 ng/kg per min) raised plasma concentrations of fentanyl to 3.37 ng/mL in a linear fashion at 20 min. There was a fall in core temperature of 0.7°C and, although no apparent depression of ventilation or fall in arterial or coronary sinus PO2, there was a rise in PCO2 and H+ concentration. Some dogs salivated and panted transiently. Thus, fentanyl may reset temperature regulation in low doses but, at higher doses, is associated with metabolic acidosis.
5. In sinus rhythm, the arterial pressure of the dogs fell slightly, then rose to 115% of resting control. Circumflex flow and conductance rose early, then conductance steadily declined to 83%. Heart rate fell, then rose before returning to pre‐infusion levels. The early circumflex coronary vasodilator effects, but not the later vasoconstrictor effects, were reduced in dogs with paced hearts.
6. In dogs with paced hearts, a dose–effect study using 138, 275, 550 and 1100 ng/kg per min fentanyl suggested that, at low plasma concentrations of 1–2 ng/mL, vasodilatation does occur in both coronary and systemic circulations; however, at higher doses, intense coronary and systemic vasoconstriction supervenes.
7. The dose–response effect of fentanyl on arterial baroreflex control of circumflex conductance was examined during the immediate 8 s circumflex vasodilator response to a step rise in aortic pressure caused by inflation of an intra‐aortic balloon. At low plasma concentrations of fentanyl, baroreflex control of circumflex conductance appears to be enhanced but, with increasing plasma concentrations of fentanyl, appears to be depressed.
8. Therefore, the effects of fentanyl are dose dependent. At low plasma concentrations, left ventricular blood flow and its baroreflex control is enhanced but, at higher concentrations, it is depressed.