1 Neuromuscular blocking drugs (NMBD's) are known to produce cardiovascular side e ects manifesting as brady/tachycardias. In this study we have examined the interaction of a range of steroidal NMBD's with recombinant human m1 ± m5 muscarinic receptors expressed in Chinese hamster ovary cells. Our main hypothesis is that NMBD's may interact with m2 (cardiac) muscarinic receptors. 2 All binding studies were performed with cell membranes prepared from CHO m1 ± m5 cells in 1 ml volumes of 20 mM HEPES, 1 mM MgCl 2 at pH 7.4 for 1 h. Muscarinic receptors were labelled with [ 3 H]-NMS and displacement studies were performed with pancuronium, vecuronium, pipecuronium, rocuronium and gallamine. In addition a range of muscarinic receptor subtype selective reference compounds were included. In order to determine the nature of any interaction the e ects of pancuronium, rocuronium and vecuronium on methacholine inhibition of forskolin stimulated cyclic AMP formation in CHO m2 cells was examined. Cyclic AMP formation was assessed in whole cells using a radioreceptor assay. All data are mean+s.e.mean (n55). 50 ) by pirenzepine in CHO m1 membranes (7.97+0.04), methoctramine in CHO m2 membranes (8.55+0.1), 4-diphenylacetoxy-Nmethyl piperidine methiodide (4-DAMP) in CHO m3 membranes (9.38+0.03), tropicamide in CHO m4 membranes (6.98+0.01). 4-DAMP, pirenzepine, tropicamide and methoctramine displaced [ 3 H]NMS in CHO m5 membranes with pK 50 values of 9.20+0.14, 6.59+0.04, 6.89+0.05 and 7.22+0.01 respectively. These data con®rm homogenous subtype expression in CHO m1 ± m5 cells. 5 [ 3 H]NMS binding was displaced dose-dependently (pK 50 ) by pancuronium (m1, 6.43+0.12; m2, 7.68+0.02; m3, 6.53+0.06; m4, 6.56+0.03; m5, 5.79+0.10), vecuronium (m1, 6.14+0.04; m2, 6.90+0.05; m3, 6.17+0.04; m4, 7.31+0.02; m5, 6.20+0.07), pipecuronium (m1, 6.34+0.11; m2, 6.58+0.03; m3, 5.94+0.01; m4, 6.60+0.06; m5, 4.80+0.03), rocuronium (m1, 5.42+0.01; m2, 5.40+0.02; m3, 4.34+0.02; m4, 5.02+0.04; m5, 5.10+0.03) and gallamine (m1, 6.83+0.05; m2, 7.67+0.04; m3, 6.06+0.06; m4, 6.20+0.03; m5, 5.34+0.03). 6 Cyclic AMP formation was inhibited dose dependently by methacholine in CHO m2 cells pEC 50 for control and pancuronium (300 nM) treated cells were 6.18+0.34 and 3.57+0.36 respectively. Methacholine dose-response curves in the absence and presence of rocuronium (1 mM) and vecuronium (1 mM) did not di er signi®cantly. Pancuronium, vecuronium and rocuronium did not inhibit cyclic AMP formation alone indicating no agonist activity. 7 With the exception of rocuronium there was a signi®cant interaction with m2 muscarinic receptors with all NMBD's at clinically achievable concentrations suggesting that the brady/tachycardias associated with these agents may result from an interaction with cardiac muscarinic receptors. Furthermore pancuronium at clinically achievable concentrations antagonised methacholine inhibition of cyclic AMP formation in CHO m2 cells further suggesting that the tachycardia produced by this agent results from muscarinic antagonism. The mech...

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SummaryA 57-year-old man with recurrent depression, resistant to drug therapy, was scheduled for a course of eight electroconvulsive therapy treatments. The patient had undergone seven treatments without incident over the previous 3 weeks. Immediately following the final treatment, the patient suffered cardiovascular collapse, culminating in cardiac arrest with electromechanical dissociation. Despite resuscitative measures, the patient died. Post-mortem examination found the cause of death to be cardiac tamponade, secondary to cardiac rupture.Keywords Anaesthesia; electroconvulsive therapy. Complication; death. Heart; rupture.. ..................................................................................... Correspondence to: Dr P. B. Ali Accepted: 13 March 1997 Electroconvulsive therapy (ECT) remains widely used in psychiatric practice. Primarily a treatment for endogenous depression resistant to drug therapy, it has been used with variable degrees of success in the treatment of other psychiatric disorders [1, 2]. It has been estimated that over 200 000 ECT treatments are performed each year in the UK [3]. Both the physical and the physiological consequences of the induced seizure are attenuated, to a variable degree, by provision of general anaesthesia and muscular paralysis; this 'modified ECT' is considered to be safe. While associated with minor morbidity, the estimated mortality is low and varies between 0.003 and 0.03% [1, 2]. Cardiovascular complications are the main cause of mortality. Case historyA 57-year-old male with a recurrent depression resistant to drug therapy was scheduled for a course of eight ECT treatments. Co-operative, although vague, the patient reported no serious medical problems and there were no adverse cardiac risk factors. Base line blood analyses were normal and the ECG showed sinus rhythm with normal axis and no evidence of conduction block or ischaemia. His medication at the time of treatment was carbamazepine 200 mg bd. and moclobemide 300 mg bd.Before each treatment the morning dose of moclobemide was omitted.Seven previous treatments had been completed without serious incident. For the final treatment, as before, intravenous access was secured and patient monitoring attached (noninvasive blood pressure, ECG and oximetry). After pre-oxygenation, anaesthesia was induced with etomidate 20 mg and a 40 mg dose of suxamethonium was given. Unilateral ECT was performed and resulted in a modified seizure lasting 27 s. An oropharyngeal airway was then inserted and manual ventilation of the lungs with high flow oxygen was continued.Shortly following treatment, the patient's face was noted to have become congested. This observation coincided with that of an unrecordable blood pressure and an impalpable carotid pulse. The ECG displayed sinus rhythm (rate of 112 beat.min -1 ) and the pulse oximeter registered 97% saturation. Electromechanical dissociation (EMD) was diagnosed and cardiac massage was immediately started. Despite efforts to resuscitate the patient, his ECG deteriora...

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