Analysis of the Effects of Fentanyl in the Feline Pulmonary Vascular Bed

Abstract

The objective of this study was to test the hypothesis that fentanyl induces a depressor response in the pulmonary vascular bed of the cat and to identify the receptors involved in the mediation or modulation of these effects. The authors conducted a prospective vehicle-controlled study at a university research laboratory using intact chest preparation in adult mongrel cats. In separate experiments, the effects of diphenhydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase [COX]-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to fentanyl and other agonists in the pulmonary vascular bed of the cat. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, fentanyl induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to fentanyl were significantly attenuated after administration of diphenhydramine and naloxone. The results of the present study suggest that fentanyl has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opiate receptor sensitive pathways.

Activation of opioid μ-receptors, but not δ- or κ-receptors, switches pulmonary C-fiber-mediated rapid shallow breathing into an apnea in anesthetized rats

“…Opioids including fentanyl and its derivatives can promote the pulmonary release of histamine (Kaye et al , 2006a; Kaye et al , 2006b), which was reported to sensitize PCFs (Lee & Morton, 1993; Undem & Weinreich, 1993). Furthermore, inhaling histamine causes a rapid breathing by activating histamine H 1 or H 2 receptors of pulmonary sensory fibers in baboons (Yeates & Hameister, 1992).…”

Dyspnea Review for the Palliative Care Professional: Treatment Goals and Therapeutic Options

“…Additionally, a vasodilatory effect on pulmonary vascular pressures in animals has been demonstrated. 1 Opioids have historically been used to treat anxiety and pain, which are often an integral part of the dyspnea cycle; the positive effects on these symptoms have been extensively reviewed. 2 Proof-of-concept for the use of opioids in dyspnea was confirmed in a recent report of measured endogenous opioids during dyspnea.…”

“…Part one of this two-part series on dyspnea for the palliative care professional describes the burden and measurement of dyspnea. 1 Because of its complex biopsychosocial etiology and manifestations, dyspnea presents a particularly challenging symptom to manage-yet it is one which, nonetheless, requires an evidence-based symptom management approach. An armamentarium of both restorative and global therapies is available to address the modifiable and fixed components to dyspnea.…”

Endogenous opiates and behavior: 2009

“…Stimulation of sensory neuropeptide release by OFQ/N leads to hyperaemia in acutely inflamed rat knees (1303). Remifentanil, sufentanil and fentanyl each induced a dose-dependent vasodepressor response in the cat pulmonary vascular bed that was attenuated by naloxone and diphenhydramine, but not glibenclamide (562,564,565). In contrast, meperidine induced a dose-dependent vasodilator response in the cat pulmonary vascular bed that was attenuated by naloxone and diphenhydramine, but not glibenclamide (563).…”