Experimental Modelling of Spinal Anaesthesia in Rats

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SUMMARY Experiment I Many previous studies suggest that the correct location of the catheter tip is crucial concerning the effect obtained. However, the previous studies did not suggest a reliable method for the prediction of the location of the catheter tip before experiments on living animals. We revealed that: 1.the tips of chronic intrathecal catheters were found to be variously located in the transverse plane in the rat spinal subarachnoid space. 2.the position of the intrathecal catheter tip influences the pharmacological effects of the local anaesthetic lidocaine. 3.the paralytic and/or antinociceptive effect of a small dose of lidocaine before the experiments is a simple and reliable method for prediction of the side position of the catheter tip before rats are used in further studies of spinal systems that mediate nociception and antinociception. 4.the differences between the effects of the drug on the two sides might be very important, especially if small doses of the drug are applied and their effects are investigated on both sides.   Experiment II This was the first study to examine the antinociceptive efficacy of the optical isomers of ketamine after intrathecal administration. We demonstrated that: 1.Both racemic and S(+)-ketamine increased significantly paw withdrawal latencies in the inflamed paw. 2.The R(-)-ketamine was ineffective to reducing thermal hyperalgesia. 3.Conversely, acute pain tests did not reveal any differences between ketamine enantiomers; i.e. only the largest dose (500 µg) caused a non-stereospecific, significant increase in hot plate latency, but this dose caused supraspinal effects as well. Neither S(+)-nor R(-)-ketamine did not show any significant effect in tail flick test in applied doses. Our result suggest that, the potential advantages of using pure enantiomers rather than a racemate include a less complex and more selective pharmacodynamic profile, a higher therapeutic index, less complex pharmacokinetics, less complex drug interactions, and less complex concentration-response relationships.

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