Development of acute tolerance to the cardiorespiratory effects of alfentanil after subsequent bolus injection in conscious rats

Doorley, Brian M.; Knight, Valerie V.; Spaulding, Theodore C.

doi:10.1016/0024-3205(88)90114-2

Cited by 7 publications

(1 citation statement)

References 15 publications

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“…The fact that systemic hemodynamics were not detectably affected by the continuous infusion of fentanyl at 24 h (Table 2) could reflect the development of tolerance [6]. Alternatively, a compensatory activation of the sympatho-adrenergic system might have come into play, a possibility suggested by the higher plasma level of NE in the treated compared with the control group (Fig.…”

Section: Discussionmentioning

confidence: 97%

Cardiovascular effects of fentanyl in conscious rats

Baechtold¹,

Cavadas

Gasser³

et al. 2001

Pflügers Arch - Eur J Physiol

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The polymicrobial sepsis induced by cecal ligation and puncture (CLP) in the rat is widely used in shock research. For ethical reasons, narcotic analgesics are often administered in this model, with the potential risk of confounding effects. In conscious non-septic rats, we investigated the cardiovascular effects of a continuous i.v. infusion of fentanyl (20 µg/kg per h) administered with fluid loading (10 ml/kg per h) for 24 h, a regimen commonly applied in rat CLP. Animals were randomly allocated to receive analgesia with fluid loading (Fentanyl group), or fluid loading alone (Control). All endpoints were assessed after 24 h of infusion. At that time, Control animals had mild respiratory alkalosis, which was essentially abolished by fentanyl. Analgesia mildly elevated the plasma norepinephrine levels [median (interquartile range): Control 232 pg/ml (0-292), Fentanyl 302 pg/ml (234-676), P=0.045] but was devoid of any effect on blood pressure, heart rate, cardiac output (mean ±SD: Control 388±61 ml/kg per min, Fentanyl 382±62 ml/kg per min, P=0.87) and indices of left ventricular function derived from high-fidelity recordings of left ventricular pressure (dP/dt max : Control 11782± 2324 mmHg/s, Fentanyl 12107±2816 mmHg/s, P=0.77). In ex vivo experiments carried out immediately after animal sacrifice, no differences were noted between the Control and Fentanyl groups in the sensitivity of endothelium-intact aortic rings to norepinephrine-induced vasoconstriction Fentanyl 8.83±0.26, P=0.52) or acetylcholine-induced vasodilatation (-logEC 50 : Control 7.00±0.37, Fentanyl 7.06±0.26± 0.53, P=0.75). In conclusion, the present data provide no contraindication, and even some support for the ethical use of a high dose i.v. infusion of fentanyl in cardiovascular studies of conscious catheterized rats undergoing CLP or other painful procedures.

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Section: Discussionmentioning

confidence: 97%