Interaction of edrophonium with muscarinic acetylcholine M2 and M3 receptors.

BACKGROUND: It has been reported that edrophonium can antagonize the negative chronotropic effect of carbachol. This study was undertaken to evaluate in detail the interaction of edrophonium with muscarinic Mz and M3 receptors. METHODS: A functional study was conducted to evaluate the effects of edrophonium on the concentration-response curves for the negative chronotropic effect and the bronchoconstricting effect of carbachol in spontaneously beating right atria and tracheas of guinea pigs. An electrophysiologic study was conducted to compare the effects of edrophonium on carbachol-, guanosine triphosphate (GTP)gama S-, and adenosine-induced outward K+ currents in guinea pig atrial cells by whole cell voltage clamp technique. A radioligand binding study was conducted to examine the effects of edrophonium on specific [3HIN-methylscopolamine (NMS) binding to guinea pig atrial (M2) and submandibular gland (M3) membrane preparations, and on atropine-induced dissociation of [3H]NMS. RESULTS: Edrophonium shifted rightward the concentration-response curves for the negative chronotropic and bronchoconstricting effects of carbachol in a competitive manner. The pA2 values for cardiac and tracheal muscarinic receptors were 4.61 and 4.03, respectively. Edrophonium abolished the carbachol-induced outward current without affecting the GTPgamma S- and adenosine-induced currents in the atrial cells. Edrophonium inhibited [3H]NMS binding to M2 and M3 receptors in a concentration-dependent manner. The pseudo-Hill coefficient values and apparent dissociation constants of edrophonium for M2 and M3 receptors were 1.02 and 1.07 and 21 and 34 microM, respectively. Edrophonium also changed dissociation constant values of [3H]NMS without affecting its maximum binding capacities. CONCLUSION: Edrophonium binds to muscarinic M2 and M3 receptors nonselectively, and acts as a competitive antagonist.

[Continuous monitoring of hemoglobin oxygen saturation of the hepatic vein in patients undergoing laparoscopic cholecystectomy].

We monitored of hemoglobin oxygen saturation of the hepatic vein (ShvO2) continuously in 6 patients undergoing laparoscopic cholecystectomy under inhalation anesthesia only, and in 6 patients under combined epidural and inhalation anesthesia. In inhalation anesthesia only group, arterial blood pressure increased and ShvO2 values decreased immediately after intraperitoneal insufflation with CO2, demonstrating the mean lowest ShvO2 value of 25 percent. In combined anesthesia group, arterial blood pressure and ShvO2 values were unchanged after the intraperitoneal insufflation compared with values obtained before the insufflation. The results indicate that hepatic blood flow may be better preserved with combined epidural and inhalation anesthesia than with inhalation anesthesia only, suggesting that sympathetic block by epidural anesthesia may contribute to this favorable effect on ShvO2.

[A case of rectal excision in a patient with cervical spinal cord injury of chronic stage].

A 63-year-old man, scheduled for a Hartmann's procedure, sustained a cervical injury with resultant complete motor and sensory loss below the fourth cervical segment 39 years prior to admission. Anesthesia was induced with propofol 70 mg, vecuronium bromide 5 mg and an endotracheal tube was placed in the trachea. Anesthesia was maintained with nitrous oxide/oxygen and fentanyl. Ventilation was controlled to maintain normocapnea. We did not employ epidual anesthesia due to inability to flex the spine. We administered fentanyl to control hypertension, but it led to hypotension. And about 500 ml of bleeding also caused hypotension. These episodes of hypotension are associated with hypovolemia and instability of vascular tone. To control hypotension, we finally selected continuous intravenous administration of norepinephrine. The manifestations of cardiovascular instability during surgery in chronic stage of cervical spinal cord injury is not only hypertension associated with autonomic hyperreflexia, but also hypotension associated with instability of vascular tone and hypovolemia.

ATP-induced ventricular asystole and hypotension during endovascular stenting surgery.

PURPOSE: To describe four cases of endoluminal stenting surgery in which adenosine 5'-triphosphate (ATP) was used to arrest the heart for accurate placement of the stent-graft. CLINICAL FEATURES: Four patients with descending thoracic aortic aneurysm were anaesthetized for deployment of a self-expanding stent-graft. Maintenance of general anaesthesia was performed with isoflurane and nitrous oxide in three patients, and with fentanyl and propofol in another. An initial trial of 20 mg ATP was administered via a central venous catheter as rapidly as possible, and produced third degree AV block of 8 +/- 1.7 sec and 59.7 +/- 17.5 sec hypotension, mean blood pressure < 60 mmHg, in three patients. The time to onset of AV block was 15.7 +/- 6.7 sec. In these patients, deployment of the stent-graft was performed during ventricular asystole produced by 30 mg ATP, which produced 16.3 +/- 2.1 sec third and second degree AV block. In one patient anaesthetized with fentanyl and propofol, 20 mg ATP did not change AV conduction. However, after 10 mg edrophonium, 20 mg ATP produced 9 sec third degree AV block. In all cases, heart rate and PQ interval were restored to the pre-drug control level within 50 sec after the commencement of AV block. There were no clinical complications related to this procedure in any patient. CONCLUSION: ATP is a convenient and suitable agent to produce transient ventricular asystole for the precise deployment of a self-expanding stent-graft. Co-administration of a parasympathomimetic agent might potentiate the inhibitory effect of ATP on AV conduction.

A comparison between chronotropic effects of neostigmine and edrophonium in isolated guinea pig right atrium.

Bradycardia is one of the inevitable and undesirable responses when the muscle weakness induced by nondepolarizing muscle relaxants is reversed by AChE inhibitors. The current study was designed to compare the bradycardiac effects of the two AChE inhibitors used widely in clinical anesthesia, neostigmine and edrophonium. Isolated, spontaneously beating guinea pig right atrial preparations were used as the experimental model, and in some cases, electrical field stimulation was utilized to stimulate parasympathetic nerve terminals within the atria. Neostigmine decreased the spontaneously beating rate in a concentration-dependent manner at concentrations up to 10 microM. At higher concentrations, the agent restored the beating rate to the predrug control level. Atropine abolished the biphasic response of the atrium to neostigmine. In contrast, edrophonium had no effect on the spontaneous beating rate. However, edrophonium (3 microM) potentiated the field stimulation-induced negative chronotropic effect. Tetrodotoxin did not inhibit the chronotropic effect of neostigmine. Both neostigmine and edrophonium at higher concentrations inhibited the negative chronotropic effect of carbachol. In conclusion, neostigmine possesses potential dual effects on cardiac muscarinic ACh receptors. Low concentrations of neostigmine may stimulate the receptors directly, and at higher concentrations neostigmine may act as an antimuscarinic agent. On the other hand, edrophonium may inhibit the cardiac muscarinic ACh receptors exclusively without stimulating the receptors. These results could at least partially explain the difference between the bradycardiac effects of the agents observed clinically.