Vecuronium-Induced Depression of Phrenic Nerve Activity During Hypoxia in the Rabbit

Abstract

We investigated the effects of a close carotid injection of vecuronium on changes in phrenic nerve activity during different states of oxygenation. Experiments were performed on normothermic and mechanically ventilated adult New Zealand White rabbits with a tracheostomy under continuous thiopental infusion. Carotid arteries and carotid bodies were identified bilaterally followed by glomectomy on the contralateral side and positioning of a lingual artery catheter with its tip located in the carotid bifurcation on the ipsilateral side. From the dissected ipsilateral C-4 nerve root, changes in integrated phrenic nerve activity (IPA) were recorded after isocapnic step reductions from hyperoxia to normoxia (fraction of inspired oxygen [FIO2] 0.21, normoxic challenge) and from hyperoxia to moderate hypoxia (FIO2 0.15, hypoxic challenge) immediately after a close carotid bolus injection of either normal saline or 1 or 10 microgram of vecuronium. Arterial blood gases were analyzed during each ventilatory state. Phrenic nerve response to hypoxia expressed as chemosensitivity (Sch) was computed as the relative change in phrenic nerve activity per unit decrease in arterial oxygen saturation (Sao2), that is: Sch = (IPA challenge/IPA hyperoxia) - 1/Sao2 hyperoxia - Sao2 challenge. Hypoxic challenges were associated with reduced phrenic nerve response (Sch) after injection of 1 and 10 micrograms of vecuronium compared with normal saline. During normoxic challenges, no change occurred after 1 microgram, but reduced chemosensitivity was seen after 10 micrograms of vecuronium. We conclude that vecuronium depresses phrenic nerve activity during hypoxia.

Hypoxic ventilatory response after rocuronium‐induced partial neuromuscular blockade in men with obstructive sleep apnoea

“…Our main result of a specific depression of HVR but not HCVR with partial neuromuscular blockade is consistent with previous work and as previously shown [8,9,[35][36][37][38]…”

Reply

“…Hence, we think that there is sufficient information to answer the first issue raised by Dr Kopman and to support the opinion that even very low concentrations of a neuromuscular blocking agent (e.g. TOF ratios of 0.70) may markedly interfere with normal chemoreceptor oxygen sensing (1–7).…”

“…In a series of human (1–3) and animal experiments (4, 5), we have demonstrated that neuromuscular blocking agents depress the hypoxic ventilatory response, mainly via an interaction with the oxygen‐sensing carotid body chemoreceptor. This depression is seen during a partial neuromuscular block and seems to follow the same time course of action as the classical neuromuscular block in skeletal muscle tissue.…”

Oxygen sensing in the carotid body: inhibited hypoxic respiratory drive with muscle relaxant

“…A possible pathway has been suggested by blocking the nicotinic ACh receptors on type I glomus cells in the rat [8]. In addition, Wyon and colleagues [9] demonstrated that hypoxia-induced phrenic nerve activities were partially blocked by arterial injection of vecuronium near the carotid body in the anesthetized rabbit. However, the importance of cholinergic signal transmission during hypoxia in the carotid body is still controversial.…”