No abstract

The pharmacokinetic disposition of xylazine hydrochloride is described after both intravenous and intramuscular injection of a single dose, in four domestic species: horse, cattle, sheep and dog, by an original high performance liquid chromatographic technique. Remarkably small interspecific differences are reported. After intravenous administration, systemic half-life (t1/2 beta) ranged between 22 min (sheep) and 50 min (horse) while the distribution phase is transient with half-life (t1/2 alpha) ranging from 1.2 min (cattle) to 5.9 min (horse). The peak level of drug concentration in the plasma is reached after 12-14 min in all the species studied following intramuscular administration. Xylazine bioavailability, as measured by the ratios of the areas under the intravenous and intramuscular plasma concentration versus time curves, ranged from 52% to 90% in dog, 17% to 73% in sheep and 40% to 48% in horse. The low dosage in cattle did not permit calculation. Kinetic data are correlated with clinical data and the origins of interspecific differences are discussed.

Despite considerable progress in the knowledge of human colonic motor function, the relationships between electrical and mechanical activity, their significance in regard to transit of digesta, and their temporal daily distribution in health and disease remain uncertain.' Previous attempts to evaluate electrical activity of the colon in man have allowed the identification of two distinct slow-wave rhythms with frequencies of 9-12 and 2-5-3.5 c/min respectively2-4 and, in one report, spike potentials were found to be superimposed on the higher slow-wave rhythm.2 Whereas the low frequency slow wave has the same incidence and frequency along the whole colon, the higher frequency slow wave has a greater incidence in the right colon, although its frequency is higher in the left colon.5 Lack of further information has been due to the technical difficulty of attaching clip or suction electrodes to the proximal colon. Failure to achieve adequate records of spiking activity was also due to the use of long time constants

SUMMARY1. A method is described in the conscious sheep for recording oscillographically the electrical potentials led from enamelled stainless-steel wires implanted in the wall of the stomach and intestine.2. Slow waves characterized by cyclically recurring and rhythmic fluctuation in voltage have been recorded, together with the superimposed fast activity or burst of spikes when the muscle is contracting. The whole activity comprised a distinguishable pattern of grouped discharge which is synchronous with mechanical events within different regions of the alimentary tract.3. Grouped discharge occurs at a regular frequency of 7/min in the pyloric part of the abomasum and 18/min from the intestine, but 13/min from the middle duodenum and proximal ileum. Only the major grouped discharges of the fore-stomach is correlated with the orderly sequential movements of the reticulum and rumen. 4. The relationship between electrical and mechanical activity of the reticulo-rumenal movements was examined at rest, and during feeding and ruminating.5. Electrical correlates of motor activity in the small bowel were investigated under different dietary regimens.

The pharmacokinetics of Dexamethasone (DXM) was studied in four cows all of which received DXM alcohol and DXM 21 isonicotinate (as a solution) by the intravenous and intramuscular routes. Concentrations of DXM and cortisol were determined using high performance liquid chromatography. An additional study was made in a second group of four cows which received intramuscular DXM 21 isonicotinate suspension for the assessment of DXM suppression of adrenal gland function. This was determined by measurements of base-line and ACTH-stimulated cortisol concentrations, before and following DXM administration. Following intravenous administration, the disposition kinetics of both formulations were described by a two-compartment open model. The half-times of elimination were similar; 335 and 291 min, respectively, for DXM alcohol and DXM 21 isonicotinate. All other pharmacokinetic parameters were not statistically different indicating that DXM was almost totally available (from DXM 21 isonicotinate). Following intramuscular administration, no significant difference in parameters was observed between the two formulations. Peak plasma concentrations were reached at 3 to 4 h post injection and bioavailability was approximately 70%. DXM was not detected in the plasma after the intramuscular administration of the suspension. The mean control plasma cortisol concentration was 8.8 +/- 3.03 ng/ml. Following intravenous and intramuscular administrations of DXM alcohol and DXM 21 isonicotinate (solution), cortisol concentrations initially increased. However, at 120 min (intravenous) and 2-4 h (intramuscular), concentrations were negligible; 24-72 h and 48-96 h, respectively elapsed before concentrations returned control values. Following DXM 21 isonicotinate (suspension) there was no initial increase and concentrations had not returned to normal in all four cows until 52 days post administration. Similarly, ACTH-stimulated plasma cortisol concentrations decreased progressively and significantly post administration. At 52 days, response to ACTH was normal in all animals.

Electrical spiking activity of the duodenum and jejunum was recorded from chronically implanted electrodes in rats during volatile or barbiturate anesthesia and following laparotomy. The normal pattern of electrical spiking activity in the fasted rat, with myoelectric complexes at 15-min intervals, was transiently replaced by quiescence during ethyl ether anesthesia. A slight increase in irregular spiking activity occurred after induction with pentobarbital, and the only effect of thiopental anesthesia was a reduction in the velocity of propagation of the complexes by 20%. Under barbiturate anesthesia, incision of the skin did not inhibit myoelectric activity, but incision of each abdominal muscle layer had an immediate and transient inhibitory effect; the deeper the layer, the longer was the inhibition. Peritoneal incision consistently produced inhibition of spiking activity which was prolonged by exposure of the bowel to air and intestine handling. The inhibitory effects produced by surgery persisted after vagotomy or transection of the spinal cord at the thoracic level but disappeared after splanchnicectomy. The above results suggest that a somatovegetative reflex with efferent pathways in the splanchnic nerves is involved in the first stage of operative inhibition of intestinal myoelectric complexes.

SUMMARY1. Spiking activity of the small intestine in the conscious dog and sheep was recorded continuously from electrodes chronically implanted on the jejunum and summed at intervals of 20 sec. The activity was related to the transit time and flow rate of intestinal contents as estimated by phenol red and by dilution of continuous marker infusions respectively. Also in some sheep the flow of digesta was measured directly from a cannula in the proximal part of the jejunum, and also by use of an electromagnetic flow meter.2. In the fasted dog and in sheep on a normal diet the intestinal activity was characterized by a migrating myo-electric complex comprising an irregular phase followed by a regular phase. These migrating myoelectric complexes occurred regularly after a period of inactivity at a frequency of 15-20/24 hr. In dogs after feeding, a continuous spiking activity appeared and persisted for periods of 7-8 hr. This was associated with much higher rates of flow and shorter transit times than were observed during fasting. In sheep, continuous spiking activity could be induced by intravenous injection of 5-hydroxytryptophan and this, similarly, was accompanied by a more rapid flow and a shorter transit time than recorded during the control period.3. In both species the longest transit time occurred when a phenol red bolus was injected during the period of electrical inactivity. Relatively short transit times were observed when the bolus was administered just before the period of regular spiking activity.4. When relaxation of the bowel was induced by intraperitoneal injection of hypertonic saline there was no spiking activity and the transit time for the infused solution was greatly lengthened, especially in the sheep. A noticeable flow of digestive contents persisted in the dog.5. In the sheep the intestinal contents flowed intermittently during 70 L. BUENO, J. FIORAMONTI AND Y. RUCKEBUSCH periods of 10-15 min and at the same frequency as the migrating myo-electric complex. Two thirds of this flow took place in the 4-6 min immediately preceding the periods of irregular spiking activity. 6. It is concluded that in the fasted dog and in the sheep the migrating myo-electric complex controls the pressure gradients on which the flow of intestinal contents depends. This is accomplished in the main by the prolonged phase of irregular spiking activity, and it is suggested that the regular spiking activity which follows it, though not in itself propulsive, serves as a barrier to prevent backflow of digesta into the quiescent part of the intestine. When continuous spiking activity is induced, by feeding in the dog and by injection of 5-hydroxytryptophan in the sheep, no part of the intestine is quiescent and the transit time is shortened by the incessant irregular spiking activity.

SUMMARY1. The electrical activity of the small intestine of conscious dogs, rabbits and sheep was recorded by means of chronically implanted electrodes and was related to mechanical changes in the bowel.2. A pattern of activity characteristic of segmental contractions (a prolonged series of bursts of spike activity superimposed on the basic electrical rhythm) was recorded successively at consecutive sites along the small intestine. This activity was as pronounced in the rabbits and sheep which were fed ad lib. as in the dogs which were fasted for 12 hr.3. The segmental contractions began in the duodenum and had a frequency of 15-20/24 hr. As they passed along the intestine, their velocity diminished and in the rabbits and sheep this was associated with an increased duration of activity. Most of the contractions reached the terminal ileum taking 1 5-2 hr in each of the species despite the differences in the length of the small intestine.4. The propagation of segmental contractions appears to be a normal and common activity of the intact bowel and it may have a propulsive as well as a mixing function.