Sotalol is not only a beta blocker but a class III antiarrhythmic drug. Its possible antifibrillatory activity was therefore investigated in both the ventricles and atria of dog heart in situ, since vulnerability to fibrillation is not the same in both these parts of the myocardium. Fibrillation threshold was measured concurrently with the duration and amplitude of monophasic action potential, the effective refractory period, the conduction time in the contractile fibres, and after fibrillation had been triggered the fibrillation rate. Variables were measured at 5 and 10 min after sotalol had been given intravenously in closed chest dogs in three doses (1, 1, and 2 mg X kg-1) at 15 min interval. Sotalol produced a rise in fibrillation threshold that occurred simultaneously with a prolongation in monophasic action potential duration and effective refractory period of the contractile fibres and a slowing in fibrillation rate, whereas conduction time was not affected. The changes appeared, however, to be less pronounced in the ventricles than in the atria, in which vulnerability to fibrillation, normally increased by vagal tone, had been previously enhanced by acetylcholine. Sotalol antagonised the changes due to acetylcholine. In both the atria and the ventricles the first dose (1 mg X kg-1), which produced plasma concentrations of approximately 2 micrograms X ml-1 10 min after injection, produced a submaximal effect. Nevertheless, subsequent administrations increased the beneficial effects but not in proportion to the dose and plasma concentrations.
SummaryEpidural blood patch is the gold standard treatment for post-dural puncture headache, although hydroxyethyl starch may be a useful alternative to blood if the latter is contraindicated. The aim of this experimental study was to assess whether hydroxyethyl starch given via an indwelling intrathecal catheter resulted in clinical or histopathological changes suggestive of neurotoxicity. The study was conducted in rats that were randomly allocated to receive three 10-ll injections on consecutive days of either saline or hydroxyethyl starch administered via the intrathecal catheter. Eight rats were given injections of saline 0.9% and 11 were given 6% hydroxyethyl starch 130/0.4 derived from thin boiling waxy corn starch in 0.9% sodium chloride (Voluven â ). Daily clinical evaluation, activity measured by actimetry and neuropathological analysis of the spinal cord were subsequently performed to assess for signs of neurotoxicity. No clinical or actimetric changes were observed in either group following intrathecal saline or hydroxyethyl starch administration. Histopathological examination showed non-specific changes with no differences between the two groups. This experimental study in the rat suggests that repeated intrathecal injection of hydroxyethyl starch is not associated with neurotoxicity.
The results of the current study indicate that intrathecal injection of HES in rats does not induce any clinical or histopathological evidence of long-term neuronal toxicity. Further safety studies in animals are warranted before HES might be considered a safe alternative to the classic epidural blood patch.
Effects of mild hyperkalemia on conduction velocity, effective refractory periods (ERPs) and sinus rate were studied on 16 anesthetized dogs, using endocavitary His bundle recordings, the extrastimulus method and standard electrocardiogram. Six dogs were placed under acetylcholine infusion (300 micrograms/kg/min) (ACh group), 10 received atropine sulfate 0.2 mg/kg intravenously (atropine group). Intraventricular conduction time, ventricular ERP and QRS duration of the EKG were studied on 7 other open-chested dogs (ventricular group). During a 60 min potassium chloride infusion (0.025 mmol/kg/min, 30 min, then 0.05 mmol/kg/min, 30 min), following observations were made: - In the ACh group, AV node conduction time (A-H interval) decreased by 20% and AV node ERP by 17%, whereas, in the atropine group, the former parameter was not affected and atrial ERP increased by 29%. - At the same time, sinus rate increased in the ACh group and was unaffected in the atropine group. - Conduction times in atrial contractile tissue (S-A interval), His-Purkinje system (H-V interval) and ventricular contractile tissue, like ventricular ERP, exhibited no variation or very slight, occasionally biphasic variations under both conditions. These results can be accounted for by an "anticholinergic" effect of mild hyperkalemia which is discussed.
The effects of verapamil were studied in anaesthetised dogs administered dextromoramide intrathecally to provide background vagal tone. Measurements were made of spontaneous heart rate, and, in paced hearts, of conduction times in atrial muscle, the atrioventricular node (A-V node) and His-Purkinje system by means of His bundle potential recording. The effective refractory period (ERP) of A-V node was measured by the extrastimulus method. In atropinised and vagotomised animals, verapamil reduced sinus rate and increased A-V nodal conduction time. In dogs high vagal tone after dextromoramide, however, verapamil increased sinus rate and reduced A-V nodal ERP. After dextromoramide alone, A-V block was observed at an atrial pacing rate of 150 beats X min-1, but after verapamil 1:1 A-V conduction was restored. The decrease in conduction velocity in the A-V node due to ACh was neither attenuated nor enhanced by verapamil.
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