PubMed · 14823463
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W F DORWARD. 1951-04-07. Concussed or drunk?. https://pubmed.ncbi.nlm.nih.gov/14823463/
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BACKGROUND: Atrial tachyarrhythmias (AT) frequently complicate the perioperative period. Alcohol intoxication is a recognized causative factor for dysrrhythmias. We studied the effects of propofol and thiopental on atrial electrophysiology and vulnerability to AT in a closed-chest porcine model in which AT are facilitated by ethanol. METHODS: Thirty-eight pigs were randomly assigned to thiopental (T-group, n=19) or propofol (P-group n=19). All animals were assigned to undergo a right atrial electrical stimulation protocol (RASP) at baseline. Thirty pigs were assigned to undergo additional RASP during ethanol infusion, while the remaining eight were assigned to undergo additional RASP during saline infusion (control group). We analysed effective refractory period (ERP), and intra-atrial conduction interval (ICI) (between atrial sites 4 cm apart), at several cycle lengths (CL). RESULTS: There were no significant differences at baseline. During ethanol infusion, propofol produced a greater rate-dependent decrease in excitability, manifested by a longer minimum paced CL with 1:1 atrial capture: 145 (11) vs 164 (27) ms in the T- and P-group, respectively (P=0.01). Propofol was associated with a greater rate-related slowing in conduction: difference between ICI at CL of 300 ms and ICI at minimum CL: 30 ms in P-group and 22 ms in T-group (P<0.03). In the P-group we observed a longer duration of induced arrhythmias (145 (131) vs 74 (91) s, P<0.03) and a higher proportion with atrial flutter (AFl) (76 vs 19%, P<0.001). CONCLUSIONS: Propofol in this model was more arrhythmogenic than thiopental, as manifested by a longer duration of induced arrhythmias, particularly AFI.
Alcohol intoxication alters coordination and motor skills, and this is responsible for a significant number of traffic accident-related deaths around the world. Although the precise mechanism of action of ethanol (EtOH) is presently unknown, studies suggest that it acts, in part, by interfering with normal cerebellar functioning. An important component of cerebellar circuits is the granule cell. The excitability of these abundantly expressed neurons is controlled by the Golgi cell, a subtype of GABAergic interneuron. Granule cells receive GABAergic input in the form of phasic and tonic currents that are mediated by synaptic and extrasynaptic receptors, respectively. Using the acute cerebellar slice preparation and patch-clamp electrophysiological techniques, we found that ethanol induces a parallel increase in both the frequency of spontaneous IPSCs and the magnitude of the tonic current. EtOH (50 mm) did not produce this effect when spontaneous action potentials were blocked with tetrodotoxin. Recordings in the loose-patch cell-attached configuration demonstrated that ethanol increases the frequency of spontaneous action potentials in Golgi cells. Taken together, these findings indicate that ethanol enhances GABAergic inhibition of granule cells via a presynaptic mechanism that involves an increase in action potential-dependent GABA release from Golgi cells. This effect is likely to have an impact on the flow of information through the cerebellar cortex and may contribute to the mechanism by which acute ingestion of alcoholic beverages induces motor impairment.
Identification of genetic and physiological mechanisms underlying a drug's or mutation's effects on motor performance could be aided by the existence of a simple observation-based rating scale of ataxia for mice. Rating scales were developed to assess ataxia after ethanol (2.75, 3.0, and 3.25 g/kg) in nine inbred mouse strains. Each scale independently rates a single behavior. Raters, blinded to dose, scored four behaviors (splay of hind legs, wobbling, nose down, and belly drag) at each of four time points after injection. The severities of hind leg splaying and wobbling were quantifiable, whereas nose down and belly dragging were expressed in all-or-none fashion. Interrater reliabilities were substantial (0.75 0 at some time), but all doses were equally effective. Incidence of nose down and belly dragging behaviors increased strain dependently after ethanol, but strains did not differentially respond to dose. Ethanol-induced splaying was modestly, and negatively, genetically correlated with wobbling. Nose down and belly dragging tended to be associated with splaying and wobbling at later times. Four distinct ataxia-related behaviors were sensitive to ethanol. Strains differed in ethanol sensitivity for all measures. Modest strain mean correlations among behaviors indicate that these behaviors are probably under control of largely different genes and that ataxia rating scales should rate separate behaviors on discrete scales.